genitourinary committee 2002...bep + hd chemo + aubmt/stem cells 1 4 2 30 1 6 5 58 s9450...

OCTOBER 25 - 28, 2002 SOUTHWEST ONCOLOGY GROUP GENITOURINARY 1

GENITOURINARY COMMITTEE

Chair: E. David Crawford, M.D. Vice Chair: Derek Raghavan, M.D., Ph.D.

Statisticians: Catherine M. Tangen, Dr.P.H.

James R. Faulkner, M.S.

Data Coordinators: Jean M. Barce, B.A. Kathy M. Bingham, C.C.R.A. Lori A. Pruski-Clark, B.A.

Protocol Coordinator: Jennifer I. Scott

Medical Oncology: Celestia S. Higano, M.D. Tumor Biology:

Pathology, T. Biology: Paul H. Gumerlock, Ph.D. Wael A. Sakr, M.D.

Radiation Oncology: Jeffrey D. Forman, M.D. Surgery: Daniel J. Culkin, M.D.

Nurse: Donna L. Berry, R.N., Ph.D.

Clinical Research

Associates: Debra W. Christie, M.B.A. Betsy A. Higgins, C.C.R.P. Susan J. Berry, R.N., B.S.N. Adel A. Guirguis, M.D. B. Various Muller, C.C.R.P.

GU Coordinator: Frances Crighton, Ph.D., R.N.

2 GENITOURINARY SOUTHWEST ONCOLOGY GROUP OCTOBER 25 - 28, 2002

CONTENTS Genitourinary Committee Agenda . . . . . . . . . . . . . . . . . . . . . . . . . 3

Initial Registrations to Therapeutic Studies. . . . . . . . . . . . . . . . . . . . . 8

Patient Registration by Study and Arm . . . . . . . . . . . . . . . . . . . . . . . 8

S9205 Biologic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

S9346 Phase III Intergroup (INT-0162) . . . . . . . . . . . . . . . . . . . . . . 12

S9442 Phase III Intergroup (T94-0086) . . . . . . . . . . . . . . . . . . . . . . 19

S9916 Phase III Intergroup . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21




S0000A Phase III Intergroup . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43

S0028 Phase II . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45

S0031 Phase II . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47

S0032 Phase II . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50

S0111 Phase II . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51

S0121 Phase II . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53

S0207 Phase II . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54

S0219 Phase II . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55

30904 Phase III Intergroup . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57



4B951 Phase III Intergroup . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63

C90003 Phase II Intergroup . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65

C9687 Phase II Intergroup . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66

E1899 Phase III: SWOG Endorsed CTSU Study. . . . . . . . . . . . . . . . . . 68

E8897 Biologic Intergroup . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70

JPR3 Phase III Intergroup . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72

JPR7 Phase III Intergroup . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74

MDA-3410 Phase III: SWOG Endorsed CTSU Study . . . . . . . . . . . . . . . 76


Genitourinary Committee Agenda

Showcased Speakers Schering Pipeline Activity Dr. Sara Zacknoen

Centocor IL-6 in GU Cancers Dr. Robert Corringham

Overview of GU Committee at CALGB Dr. Eric Small

Bladder Organ Site Chairs Drs. Petrylak (Advanced)

and Wood (Local)

Cytogenetics Liaison Dr. Wolman

Active Studies

S0028 Study of Elderly - Gemcitabine and Paclitaxel in Advanced Urothe-lial Cancer. Phase II.

Dr. Raghavan

S0031 Evaluation of ZD 1839 in Advanced Transitional Cell Carcinoma (TCC) of the Urothelium. Phase II.

Dr. Petrylak

4B951 MVAC in Organ-Confined Bladder Cancer Based on p53 Status. Phase III. (USC)

Dr. Lerner

30987 Trial Comparing Paclitaxel/Cisplatin/Gemcitabine and Cis-platin/Gemcitabine in Patients with Metastatic or Locally Advanced Urothelial Cancer. Phase III. (EORTC)

Drs. Smith and Petrylak

Closed Studies

S8710 MVAC as Neoadjuvant Followed by Cystectomy for T2, T3 and T4 TCC of the Bladder (INT 0080, EST 1887). Phase III.

Drs. Grossman and Natale

S8733 Evaluation of Operable Bladder Cancer Patients with Pre-operative Radiation + 5-FU and Inoperable Patients with Radiation + 5-FU Alone. Pilot.

Drs. Higano and Russell

S9140 Study of Oral Bropirimine Combined with Intravesical Bacillus Calmette-Guerin in Patients with Carcinoma-In-Situ of the Bladder. Phase II.

Dr. Sarosdy

S9457 Paclitaxel and Carboplatin for Advanced TCC of the Urothelium. Phase II.

Dr. Small

S9458 Evaluation of Ki-67, p53 and Angiogenesis in Patients Registered to SWOG-8710. Ancillary.

Dr. Grossman

S9809 The Effect of Fluoroquinolones on the Disease-Free Interval in Pa-tients with Stage Ta TCC of the Bladder. Phase III.

Dr. Wood


Proposed Studies

S0219 Treatment of Limited Muscle Invasive Bladder Cancer with Re-peated TURBT's and Chemotherapy. Phase II.

Drs. Lara and deVere White

S0121 Evaluation of Carboplatin, Paclitaxel, and Gemcitabine Followed by Concurrent Cisplatin and RT in Patients with Locally Advanced or Recurrent Urothelial Malignancy. Phase II.

Dr. Vaishampayan

30994 Trial Comparing Immediate Versus Deferred Chemotherapy after Radical Cystectomy in Patients with pT3-pT4 and/or N+, M0 TCC of the Bladder. Phase III. (EORTC)

Drs. Benson and deVere White

Study of Irinotecan in Patients with Advanced TCC of the Urothe-lium. Phase II.

Dr. Beer

The Role of Cox-2 Inhibition in Recurrent Superficial/Early Inva-sive TCC of the Bladder. Phase II.

Dr. Lee

Advanced Bladder/Schering 6636 Dr. Petrylak

Prostate Organ Site Chairs Drs. Hussain (Advanced)

and Thompson (Local)

Cytogenetics Liaison Dr. Brothman

Active Studies

C9687 Role of Salvage Prostatectomy for RT Failure. Phase II. (CALGB) Dr. Basler

JPR3 CAB Versus CAB + RT in T3-4, N0, M0. Phase III. (NCIC) Dr. Swanson

JPR7 Intermittent Versus Continuous Androgen Suppression in Patients with Rising PSA Following RT. Phase III. (NCIC)

Dr. Higano

S9205 Central Prostate Cancer Serum Repository Protocol. Dr. Benson

S9346 Intermittent Androgen Deprivation in Patients with Stage D2 Pros-tate Cancer. Phase III.

Dr. Hussain

S9916 Estramustine + Docetaxel Versus Mitoxantrone + Prednisone for Advanced Hormone Refractory Prostate Cancer. Phase III.

Dr. Petrylak

S9921 Adjuvant Androgen Deprivation Versus Mitoxantrone + Prednisone + Androgen Deprivation in High Risk Prostate Cancer Patients Fol-lowing Radical Prostatectomy. Phase III.

Dr. Glode

S0111 Epothilone B Analog (BMS-247550) in Hormone Refractory Pros-tate Cancer. Phase II.

Dr. Hussain

S0032 Early Oral Estramustine, Oral Etoposide, and IV Paclitaxel Com-bined with Hormone Therapy in D2 Prostate Cancer. Phase II.

Dr. Smith


Closed Studies

S8794 Adjuvant RT Following Radical Prostatectomy. Phase III. Dr. Thompson

S9024 Study of Combined Modality Therapy in T3-4, N0, M0 Adenocar-cinoma of the Prostate. Phase II.

Dr. Smalley

S9109 Neoadjuvant Zoladex and Flutamide in Bulky and Non-Bulky Clinical Stage C Carcinoma of the Prostate. Phase II.

Dr. Powell

S9426 Antiandrogen Withdrawal in Patients with Progressive Prostate Cancer. Phase II.

Dr. Sartor

S9510 Topotecan for Patients with Hormone Refractory Prostate Cancer. Phase II.

Dr. Klein

S9450 Prostate Cancer Intervention Versus Observation Trial (PIVOT). Phase III. (VAMC)

Dr. Culkin

Proposed Studies

E1899 Evaluation of Second Line Hormonal Therapy Versus Pacli-taxel/Estramustine in Asymptomatic Patients with Rising PSA after Hormonal Therapy. Phase III.

Drs. Bhoopalam and Swanson

S0113 Neoadjuvant Estramustine + Etoposide Followed by Concurrent Estramustine + RT in Locally Advanced Prostate Cancer. Phase II.

Dr. Ben-Josef

S0214 Exisulind in Non-metastatic Early Hormone Refractory Prostate Cancer. Phase II.

Dr. Lara

S0228 Randomized Screening Trial of High Dose Pulse Calcitriol, Do-cetaxel, and Estramustine vs Mitoxantrone-DPPE-Prednisone in Androgen-Independent Prostate Cancer.

Drs. Raghavan and Beer

MDA-3410 Consolidation Therapy with or without Strontium-89 Following Induction Chemotherapy in Androgen-Independent Prostate Cancer. Phase III. (MD Anderson).

Dr. Pinski

P0014 Androgen Blockade with 4 Cycles of Immediate Chemotherapy versus Androgen Blockade with Delayed Chemotherapy in Patients with High Risk, Hormone-naive Prostate Cancer. Phase III. (RTOG)

Dr. Lara

Predictors of Outcome for African American Men with Newly Di-agnosed D2 Prostate Cancer Registered to SWOG Study 9346. Ancillary.

Dr. Hussain

C90202 Early versus Delayed Zoledronic Acid to Prevent Skeletal Related Events in Men with Prostate Cancer Metastatic to Bone. Phase III. (CALGB)

Dr. Greene

Role of Hyperbaric Oxygen Therapy (HBOT) in Reducing Morbid-ity Associated with Salvage Radical Prostatectomy. Phase II.

Dr. Herman


Renal Cell Organ Site Chair Dr. Flanigan

Medical Oncology Vice Chair Dr. Lara

Cytogenetics Liaisons Drs. Lindgren and Wolman

Active Studies

30904 Radical Surgery Versus Elective Kidney Sparing Surgery for Low Stage Renal Cell Cancer. Phase III. (EORTC)

Dr. Skinner

Closed Studies

S8949 A Randomized Comparison of Nephrectomy Followed by Intron-A Versus Intron-A Alone in Patients with Advanced Renal Cell Car-cinoma. Phase III.

Dr. Flanigan

S9023 Cytogenetic and Flow Cytometry Analysis of Solid Tumors: Renal Cell Carcinoma, Companion Study to S8949. Biologic.

Drs. Whitehead, Shankey and Flanigan

S9230 Evaluation of Interleukin-4 (IL-4) in Disseminated Renal Cell Ade-nocarcinoma. Phase II.

Dr. Whitehead

S0109 Flavopiridol in Advanced Renal Cell Carcinoma. Phase II. Dr. Van Veldhuizen

Proposed Studies

C90003 Non-myeloblative Allogeneic Stem Cell Transplant for Patients with Metastatic Renal Cell Carcinoma. Phase II.

Dr. Margolin

Capecitabine plus Gemcitabine in Advanced Renal Cell Carcinoma. Phase II.

Dr. Van Veldhuizen

EGFR Inhibitor Tarceva (OSI-774) in Patients with Metastatic or Locally Advanced Papillary Histology Renal Cell Carcinoma. Phase II.

Dr. Gordon

Penile, Adrenal, and Rare Sites Organ Site Chair Dr. Culkin

Proposed Studies

S0224 Weekly Docetaxel in Patients with Advanced Epidermoid Carci-noma of the Penis. Phase II.

Dr. Beer

Taxotere for Adrenal Cell Carcinoma. Phase II. Dr. Quinn


Testis Organ Site Chair Drs. Margolin and

Logothetis

Active Studies

S9442 BEP + High-Dose Chemotherapy Versus BEP Alone in Patients with Poor and Intermediate Risk Germ Cell Tumors. Phase III. (MSKCC).

Dr. Margolin

S0207 Study of Arsenic Trioxide in Patients with Refractory Germ Cell Malignancies. Phase II.

Dr. Beer

Proposed Studies

E8897 Correlation of Histopathology, Immunohistochemistry and Quanti-tative Radiology with Outcome in Early Stage Nonseminomatous Germ Cell Tumor of the Testis. (ECOG)

Dr. Nichols

Gemcitabine + Oxaliplatinum in Testis Cancer. Phase II. Dr. Margolin

Outcomes of Treatment in Hispanic Males with Good to Intermedi-ate Risk GCT.

Dr. Raghavan

C90106 TIP versus TICE with PBSC support for resistant germ cell tumors. (CALGB)

Dr. Margolin

Cancer Control

Organ Site Chair Dr. Marshall

Active Studies

S9917 L-Selenium-Based Chemoprevention of Prostate Cancer Among Men with High Grade Prostatic Intraepithelial Neoplasia. Phase III.

Drs. Marshall and Wood

S0000 Selenium and Vitamin E Cancer Prevention Trial (SELECT). Phase III.

Drs. Lippman, Klein, and Thompson

Closed Studies

S9217 PCPT - Chemoprevention of Prostate Cancer with Finasteride (Pro-scar). Phase III.

Drs. Thompson, Brawer, and Miller

S9812 Selenomethionine in Prostate Cancer Patients Scheduled to Un-dergo Radical Prostatectomy. Pilot Study.

Dr. Sabichi

Proposed Studies

S0208 Chemoprevention of Prostate Cancer with Cox-2 Inhibitor. Phase III.

Dr. Basler


Initial Registrations to Therapeutic Studies

by 12 month Intervals GENITOURINARY COMMITTEE

0

100

200

300

400

500

600

700

800

900

1,000

Time of registration

JUL 1997JUN 1998

182658

168

34

JUL 1998JUN 1999

11025

113

86

JUL 1999JUN 2000

3754

67

258

275

JUL 2000JUN 2001

39

61

98

356

363

JUL 2001JUN 2002

48

69

135

345

297

MEMBER AFFILIATES CCOP UCOP NON-SWOG

Patient Registration by Study and Arm

GENITOURINARY COMMITTEE

Jan-June

2002 July-Dec 2001 Jan-June

2001 All Patients

S9205 Prostate Serum Repository Serum Repository 80 47 65 835 S9346 Adv Pros, Intermit Andro Dep, PhIII Induction registration

Combined Androgen Deprivation 140 156 177 1,394 Consolidation registration Intermittent Hormonal Therapy 45 50 57 359 Continuous Hormonal Therapy 41 55 56 360 86 105 113 719 S9426 Adv Pros, Antiandrogen Withdrawal, PhII Antiandrogen Withdrawal 0 0 29 259


Patient Registration by Study and Arm GENITOURINARY COMMITTEE (Continued)

Jan-June


2001 All Patients

S9442 GCT, BEP + HD Chemo vs BEP, PhIII * BEP Alone 0 2 3 28 BEP + HD Chemo + AuBMT/Stem Cells 1 4 2 30 1 6 5 58 S9450 Prostatectomy vs Observation, PhIII * Radical Prostatectomy 0 0 1 7 Expectant Management 0 0 0 12 0 0 1 19 S9809 Blad, Ta, Fluoroquinolones, PhIII Ciprofloxacin 0 0 8 55 Cephalexin 0 0 14 59 0 0 22 114 S9812 CC Pros, I-Selenomethionine, PhII Selenium 0 0 6 35 Observation 0 0 2 33 0 0 8 68 S9916 Adv Pros, Hormone Refractory, PhIII Docetaxel + Estramustine 59 60 67 317 Mitoxantrone + Prednisone 64 64 64 321 123 124 131 638 S9917 CC Pros, Selenium vs Placebo, PhIII Repeat Biopsy 56 47 42 163 Randomization X 24 14 13 52 Y 23 17 13 55 47 31 26 107 S9921 Pros, Adjuvant High Risk, PhIII Casodex + Zoladex 36 20 20 87 Mitox + Pred + Caso + Zoladex 35 20 22 88 71 40 42 175 S0028 Adv Blad, Gem + Pac in Elderly, PhII Gemcitabine + Paclitaxel 5 2 0 7 S0031 ZD1839 in Adv TCC Urothelium, PhII ZD1839 11 17 2 30 S0032 Adv Pros, CAD + Chemo, PhII CAD + Chemo 2 0 0 2


Patient Registration by Study and Arm GENITOURINARY COMMITTEE (Continued)

Jan-June


2001 All Patients

S0109 Adv Renal Cell, Flavopiridol, PhII Flavopiridol 0 38 0 38 S0111 Adv Pros, Epothilone, PhII BMS-247550 9 1 0 10 S0207 Adv Germ Cell, Arsenic, PhII Arsenic Trioxide 1 0 0 1 30904 Ren, Radical vs Partial Nephrectomy, PhIII * Radical Nephrectomy 0 1 0 1 Kidney Sparing Nephrectomy 0 0 1 1 0 1 1 2 4B951 Blad, Adj MVAC vs Obs for p53+, PhIII * Identifying p53 Status 11 1 0 12 Randomization MVAC 0 1 0 1 Observation 1 0 0 1 1 1 0 2 C9687 Pros, Salv Prost after RT, PhII * Salvage Prostatectomy 1 0 0 1 JPR3 Pros, Blockade vs Blockade + RT, PhIII * Androgen Blockade 0 1 0 18 Androgen Blockade + XRT 0 0 1 19 0 1 1 37 JPR7 Pros, Intermit vs Cont Andr Sup, PhIII * Intermit Androgen Suppression 6 5 5 34 Cont Androgen Deprivation 11 7 5 43 17 12 10 77

* For non-SWOG coordinated studies only SWOG registrations are shown.


S9205/BIOLOGIC

S9205 Biologic

Central Prostate Cancer Serum Repository Protocol

Study Coordinators: M Benson, D Petrylak, W Sakr, P Gumerlock

Statisticians: C Tangen, J Faulkner

Data Coordinator: J Barce

Date Activated: 10/1/1992

Objectives To store serum of patients with cancer of the prostate entered onto clinical trials conducted by the Southwest Oncology Group Genitourinary Committee.

To provide the serum of the above patients for specific clinical-laboratory investigations (e.g. evaluation of a new marker) outlined on separate Southwest Oncology Group protocols approved by the Genitourinary Committee Tumor Biology Subcommittee.

Patient Population Patients must be eligible for and registered to a Southwest Oncology Group protocol for carci-noma of the prostate. All patients must submit ≥ 3 ml of unthawed serum from baseline (pretreat-ment) to be eligible for this study. Patients who are subsequently ruled ineligible for the interven-tion protocol will also be ruled ineligible for this study.

Summary Statement A total of 835 specimens have been submitted from 25 studies as of June 30, 2002.

Registration by Institution Registrations ending June 30, 2002

Institutions Total Reg Institutions

Total Reg

LSU-Shreveport UCOP/LSU-Shreveport 102 Grand Rapids CCOP 9

Tulane U - UCOP/Tulane University 58 Riverside Methodist/Ohio State U 9 Henry Ford-UCOP/Henry Ford Hosp 56 Texas Tech Univ-UCOP 9 So Calif, U of-UCOP/So Calif, U of 54 UT Southwestern/UCOP 9 Oregon Hlth Sci-UCOP/Oregon Hlth Sci Univ 50 Columbus CCOP 8 Arkansas, U of-UCOP/Arkansas, U of 43 Madigan Army Med Ctr/Puget Sound 8 BAMC/WHMC-UCOP/BAMC/WHMC 33 Oklahoma, U of -UCOP/Oklahoma, Univ of 8 San Antonio, TX-UCOP/San Antonio, U of TX 25 San Francisco UCOP 8 Kansas, U of 24 Upstate Carolina 8 Kentucky, U of-UCOP/Kentucky, U of 23 Johns Hopkins Hosp 6 E Virginia UCOP 22 Mississippi, U of 6 PSOC UCOP/Puget Sound 19 New Mexico, U of 6 Wayne State U-UCOP/Wayne State Univ 19 St Charles Med Ctr/Puget Sound 6 Colorado, U of-UCOP/Colorado, U of 17 Wichita CCOP 6 Columbia-Presby UCOP 16 City of Hope Med Ctr 5 Cleveland Clin-UCOP/Cleveland Clinic OH 15 Northwest CCOP 5 Arizona, U of-UCOP/Arizona, U of 14 St Bernards Reg MC/Arkansas, U of 5 Davis, U of CA-UCOP/Davis, U of CA 14 Scott & White/TX A&M 4 Loyola/Hines VA-UCOP/Loyola University 14 Southeast CCC CCOP 4 Utah, U of - UCOP/Utah, U of 14 All Other Institutions 64 Montana CCOP 10 Total (83 Institutions) 835


S9346/III

S9346 Phase III Intergroup (INT-0162) Coordinating Group: SWOG

Intermittent Androgen Deprivation in Patients with Stage D2 Prostate Cancer

Participants: SWOG, CALGB (9594), ECOG (S9346), EORTC (30985), NCIC (JPR.8), EMMES, CTSU

Study Coordinators: M Hussain, M Eisenberger, B Miles, P Lange, E Crawford, E Small (CALGB), G Wilding (ECOG), A Akdas (EORTC), S Goldenberg (NCIC)


Data Coordinator: K Bingham


Schema

REGISTRATION

RANDOMIZE

Induction CAD7 months

PSA 4

PSA > 4 Off study

Arm A:Continuous CAD

Arm B:Intermittent CAD

Objectives To assess whether patients randomized to inter-mittent combined androgen deprivation (CAD) after seven months of induction CAD have sur-vival that is not substantially worse than patients randomized to continuous CAD.

To compare three treatment-specific symptoms, as well as physical and emotional functioning, be-tween the study arms.

To compare general symptoms, role functioning, global perception of quality of life and social functioning between the study arms.

To gather data on PSA changes following initia-tion of hormonal therapy during the induction pe-

riod. To gather detailed data on PSA changes for patients in both arms.

Patient Population Patients must have a histologically or cytologi-cally proven diagnosis of adenocarcinoma of the prostate. Patients must have clinical Stage D2 disease as evidenced by soft tissue and/or bony metastases. Patients in situations in which second primaries cannot be excluded are not eligible unless metastatic disease is histologically con-firmed (including special stains [PSA and PAP]). Patients who have already begun the use of CAD are eligible for late induction registration to the study with some restrictions (see protocol for de-tails). Patients must have elevated PSA ≥ 5 ng/ml. Patients will be eligible for randomization only if


S9346/III

they meet the PSA normalization criterion using the PSA values from the months 6 and 7 speci-mens. Only institutions using the Hybritech or Abbott PSA assays (or other assays calibrated to these assays) will be allowed to register patients to this study. Patients must have received exactly eight monthly injections of the protocol-specified LHRH analogue or the dose equivalent to be eli-gible for randomization.

Patients with a history of prior neoadjuvant or ad-juvant hormone therapy or prior finasteride treatment are eligible with some restrictions. Prior use of low-dose megace for the treatment of hot flashes is allowed.

Patients must have adequate hepatic function. Pa-tients must have a SWOG performance status of 0-2. Patients must have recovered from major in-fections and/or surgical procedures and, in the opinion of the investigator, not have significant active medical illness precluding protocol treat-ment or survival. Patients must be able to read and understand English or Spanish (or French for NCIC) in order to participate in the Quality of Life portion of the study. Patients unable to read and understand English or Spanish may be regis-tered to receive treatment only.

Stratification/Descriptive Factors Patients will be described by late induction: yes vs no. At the time of consolidation randomiza-tion, patients will be stratified by (1) performance status: 0-1 vs 2; (2) severity of disease (as speci-fied in the protocol): minimal vs extensive; and (3) prior hormone therapy: neoadjuvant hormone therapy vs finasteride vs none.

Accrual Goals The accrual goal for this study is 1,512 random-ized patients. Three formal interim analyses are planned for the primary efficacy outcome. These will be performed during the accrual period after 49%, 74%, and 94% of the patients have been randomized. The final analysis will take place two years following the completion of randomi-zation.

Summary Statement As of June 30, 2002, this study had 1,394 induc-tion registrations. Two hundred forty-nine pa-tients (18%) are currently listed as ineligible pri-marily due to insufficient information; 180 (72%) of these are potentially reversible.

Thirteen patients are not assessable for induction treatment toxicity: two because the patients re-

fused all protocol treatment and are considered major deviations, and 11 because toxicities were not evaluated during the induction period. There were 13 other major deviations due to patients not receiving the dose equivalent of exactly eight monthly injections of the LHRH analogue. Those coded with major deviations are not eligible for randomization. Eight hundred twenty-three pa-tients have been evaluated for toxicities on induc-tion treatment. One patient died of starvation due to dementia (coded as neurologic) and another died of COPD. Both were ruled as possibly re-lated to treatment. Three other Grade 5 ADR's are currently under review because death occurred within 30 days after the patient's last treatment. Five additional patients experienced Grade 4 tox-icities.

Four hundred ninety-two eligible or review pend-ing patients have gone on to continuous versus in-termittent CAD consolidation randomization. Seven patients are coded as having major devia-tions and are not assessable for toxicity. Four pa-tients randomized to the continuous arm refused all treatment, and three patients on the intermit-tent arm received no CAD because they were taken off treatment prematurely. An additional three patients are not assessable for toxicities (but are not coded as major deviations) because these patients progressed or died on the intermittent arm prior to receiving any consolidation treat-ment. One hundred eighty-six patients have been evaluated for toxicities. Fewer patients on the in-termittent arm have been evaluated for toxicities because protocol treatment is delayed until PSA increases to 20 ng or more. There have been three Grade 4 and one Grade 5 toxicities (a cardiac death for a patient with a history of cardiac dis-ease is under review) on the continuous arm, and one Grade 4 toxicity on the intermittent arm.

The Quality of Life questionnaire submission rates for patients qualifying for assessment are as follows: 8-month assessment, 84%; 11-month as-sessment, 91%; 17-month assessment, 84%; and 23-month assessment, 81%.

The current randomization rate of 17 patients per month is slightly less than what was anticipated (20 patients per month). The study has completed one-third of its accrual goal. At the current ran-domization rate, this study will be completed within five years.


S9346/III

Induction Registration By 12 Month Intervals

0

50

100

150

200

250

300

350

400

450

Time of Registration

JAN 1995DEC 1995

18JAN 1996DEC 1996

61

JAN 1997DEC 1997

96

JAN 1998DEC 1998

110

JAN 1999DEC 1999

230

JAN 2000DEC 2000

406

JAN 2001DEC 2001

333

JAN 2002DEC 2002

140

Combined Androgen Deprivation

Registration by Institution Induction Registration

Registrations ending June 30, 2002


Total Reg

ECOG 293 Birmingham, AL-UCOP 8

EORTC 254 Cleveland Clin-UCOP/Cleveland Clinic OH 8 CALGB 162 Kansas, U of 8 NCIC 99 Arkansas, U of-UCOP/Arkansas, U of 7 E Virginia UCOP 60 Ann Arbor Reg CCOP 6 Wayne State U-UCOP/Wayne State Univ 59 Kentucky, U of-UCOP/Kentucky, U of 6 So Calif, U of-UCOP/So Calif, U of 39 Loma Linda Univ/Davis, U of CA 6 LSU-Shreveport UCOP/LSU-Shreveport 37 Michigan, U of 6 Davis, U of CA-UCOP/Davis, U of CA 28 City of Hope Med Ctr 5 Loyola/Hines VA-UCOP/Loyola University 28 San Francisco UCOP 5 Henry Ford-UCOP/Henry Ford Hosp 26 Baylor College-UCOP 4 Colorado, U of-UCOP/Colorado, U of 25 Covenant Health Sys/San Antonio, U of TX 4 Tulane U - UCOP/Tulane University 21 Montana CCOP 4 Oregon Hlth Sci-UCOP/Oregon Hlth Sci Univ 18 Ozarks Reg CCOP 4 Oklahoma, U of -UCOP/Oklahoma, Univ of 17 Utah, U of - UCOP/Utah, U of 4 Columbia-Presby UCOP 15 Boulder Comm Hosp/Colorado, U of 3 PSOC UCOP/Puget Sound 14 Greenville CCOP 3 Central IL CCOP 13 Hawaii CCOP, Univ of 3 Wichita CCOP 13 Huntsville Hosp/San Antonio, U of TX 3 Virginia Mason UCOP/Virginia Mason CCOP 12 Marquette Gen Hosp/Wayne State Univ 3 Columbus CCOP 10 All Other Institutions 32 EPP 10 Total (67 Institutions) 1,394 BAMC/WHMC-UCOP/BAMC/WHMC 9


S9346/III

Registration, Eligibility, and Evaluability Induction Registration

Registrations ending June 30, 2002; Data as of July 16, 2002

Combined Androgen

Deprivation

Combined Androgen

Deprivation NUMBER REGISTERED 1,394 TOXICITY ASSESSMENT 1,145

INELIGIBLE 249 Evaluable 823 Insufficient Documentation 214 Not Evaluable 13 Irreversible 34 Too Early 309 Reversible 180 ELIG./ PEND. ELIG. 1,145 Analyzable, Pend. Elig. 133

Patient Characteristics Induction Registration



(n=1145)


(n=1145)

AGE AFFILIATION Median 70 .0 Cooperative Group 1,134 99% Minimum 39 EMMES 11 1% Maximum 94 LATE INDUCTION RACE No 931 81% White (Non-Hispanic) 708 62% Yes 214 19% Black (Non-Hispanic) 209 18% Hispanic 31 3% Asian 12 1% Pacific Islander 1 0% Native 1 0% Unknown 183 16%

Number of Patients with a Given Type and Degree of Toxicity Induction Registration


Combined Androgen Deprivation Combined

Androgen Deprivation (n=823) (n=823)

Grade

Grade

TOXICITY Unk 0 1 2 3 4 5 TOXICITY Unk 0 1 2 3 4 5 ADR 0 820 0 0 0 0 3 Lung 5 770 7 36 4 0 1 Cardiovascular 3 736 54 17 12 1 0 Metabolic 0 815 4 1 2 1 0 Dermatologic 3 764 47 8 1 0 0 Musculoskeletal 1 814 6 2 0 0 0 Ear 0 822 0 1 0 0 0 Neurologic 8 619 147 41 6 1 1 Endocrine 19 340 278 169 17 0 0 Pain 17 569 156 64 17 0 0 Eye 4 811 3 4 1 0 0 Renal/Bladder 9 715 67 26 6 0 0 Flu-like Symptoms 14 493 210 100 6 0 0 Secondary Malignancy 0 822 0 0 0 1 0 Gastrointestinal 6 695 84 30 8 0 0 Sexual/Reproductive Function 6 599 82 40 96 0 0 Hematologic 1 810 6 3 3 0 0 Syndromes 0 822 0 1 0 0 0 Hemorrhage 1 809 8 2 3 0 0 Immunological 0 816 5 2 0 0 0 MAXIMUM GRADE Infection 4 807 2 5 5 0 0 ANY TOXICITY Liver 1 772 33 9 7 1 0 Number 28 145 261 222 157 5 5


S9346/III

Consolidation Registration By 12 Month Intervals

0

50

100

150

200

250


JAN 1996DEC 1996

912

JAN 1997DEC 1997

35

38

JAN 1998DEC 1998

29

29

JAN 1999DEC 1999

42

40

JAN 2000DEC 2000

93

88

JAN 2001DEC 2001

111

107

JAN 2002DEC 2002

41

45

Continuous hormonal therapy Intermittent hormonal therapy

Registration, Eligibility, and Evaluability Consolidation Registration


TOTAL

Intermittent hormonal therapy

Continuous hormonal therapy

NUMBER REGISTERED 719 359 360

INELIGIBLE 227 114 113 Insufficient Documentation 177 90 87 Irreversible 26 15 11 Reversible 151 75 76 ELIG./ PEND. ELIG. 492 245 247 Analyzable, Pend. Elig. 108 59 49 TOXICITY ASSESSMENT Evaluable 186 63 123 Not Evaluable 10 6 4 Too Early 296 176 120


S9346/III

Patient Characteristics Consolidation Registration


Intermittent hormonal therapy (n=245)

Continuous hormonal therapy (n=247)

AGE Median

71 .0

71 .0

Minimum 46 40 Maximum 90 91 RACE White (Non-Hispanic)

168

69%

164

66%

Black (Non-Hispanic) 38 16% 49 20% Hispanic 7 3% 4 2% Asian 3 1% 2 1% Native 0 0% 1 0% Unknown 29 12% 27 11% PERFORMANCE STATUS 0-1

239

98%

241

98%

2 6 2% 6 2% DISEASE Minimal

133

54%

134

54%

Extensive 112 46% 113 46% PRIOR THERAPY Neoadjuvant

33

13%

29

12%

Finasteride 3 1% 0 0% None 209 85% 218 88%

Treatment Summary Consolidation Registration


TOTAL

Intermittent hormonal therapy

Continuous hormonal therapy

NUMBER ON PROTOCOL TREATMENT 327 172 155

NUMBER OFF PROTOCOL TREATMENT 165 73 92 REASON OFF TREATMENT Toxicity or side effects 5 0 5 Refusal unrelated to toxicity 12 2 10 Other - not protocol specified 24 13 11 Reason under review 77 40 37 MAJOR PROTOCOL DEVIATIONS 7 3 4


S9346/III

Number of Patients with a Given Type and Degree of Toxicity Consolidation Registration

Toxicities with No Entries for Grades 3 to 5 Have Been Suppressed Registrations ending June 30, 2002; Data as of July 16, 2002

Intermittent hormonal therapy Continuous

hormonal therapy (n=63) (n=123)

Grade Grade

TOXICITY ≤ 2 3 4 5 ≤ 2 3 4 5 Cardiovascular 61 2 0 0 119 1 2 1 Endocrine 62 1 0 0 121 2 0 0 Flu-like Symptoms 63 0 0 0 122 1 0 0 Gastrointestinal 62 1 0 0 123 0 0 0 Hemorrhage 63 0 0 0 122 1 0 0 Infection 62 1 0 0 123 0 0 0 Lung 62 1 0 0 122 0 1 0 Metabolic 62 1 0 0 122 1 0 0 Neurologic 63 0 0 0 122 1 0 0 Pain 60 2 1 0 121 2 0 0 Renal/Bladder 63 0 0 0 121 2 0 0 Sexual/Reproductive Function 57 6 0 0 101 22 0 0 MAXIMUM GRADE ANY TOXICITY Number

50 12 1 0

94 25 3 1


S9442/III

S9442 Phase III Intergroup (T94-0086) Coordinating Group: MSKCC

Randomized Multi Institutional Phase III Trial of BEP and High Dose Chemotherapy Versus BEP Alone in Previously Untreated Patients with

Poor and Intermediate Risk Germ Cell Tumors

Intergroup Participants: MSKCC (94-76), SWOG, CALGB (99812), ECOG (3894)

Study Coordinators: R Motzer (MSKCC), K Margolin, E Small (CALGB), C Nichols (ECOG)




Schema

RANDOMIZE

Arm A: BEP chemotherapy

Arm B: BEP chemotherapy + high dose chemotherapyand AuBMT/stem cells

Objectives To compare the efficacy of two cycles of bleo-mycin, etoposide, and cisplatin (BEP) plus two cycles of high dose carboplatin, etoposide and cyclophosphamide with autologous bone marrow transplant (AuBMT) (or stem cell infusion) to four cycles of BEP alone in previously untreated germ cell tumor (GCT) patients with poor and in-termediate risk features.

To compare the toxicity associated with early dose intensification with high dose chemotherapy and AuBMT/stem cells compared with standard chemotherapy of four cycles of BEP in previ-ously untreated poor and intermediate risk GCT patients.

To prospectively evaluate the rate of decline of serum tumor markers human chorionic gonad-otrophin (HCG) and alphafetoprotein (AFP) of patients in both arms of the study for use as post-treatment prognostic indicators. These will be correlated with complete response and survival.

Patient Population Patients must be male with either intermediate or poor risk (as defined in the protocol) germ cell tumors. Patients must have measurable or evalu-able disease. Patients must have confirmation of germ cell tumor histology.

Patients must have had no prior treatment with chemotherapy. Unless evidence of progressive disease has been documented, patients must not have had radiation therapy within 30 days of reg-istration and toxicity relative to the radiation therapy must have abated.

Patients must be at least 12 years of age and have adequate hematologic and renal function.

Stratification/Descriptive Factors Patients are stratified by (1) registering institu-tion: MSKCC vs ECOG vs SWOG vs other par-ticipating institutions; and (2) risk status: poor vs intermediate.


S9442/III

Accrual Goals The total accrual goal for this study is 270 eligi-ble patients, 135 per arm. The 270 patients will consist of 216 poor-risk and 54 intermediate-risk. Two interim analyses are planned.

Summary Statement According to MSKCC, this study had accrued 200 patients (58 registered by SWOG institu-tions) as of June 30, 2002.



Total Reg

Columbia River CCOP 5 Dayton CCOP 1

LSU-Shreveport UCOP/LSU-Shreveport 5 Hawaii CCOP, Univ of 1 Arkansas, U of-UCOP/Arkansas, U of 4 Jewish Hospital/Cincinnati MC, U of 1 City of Hope Med Ctr 4 Loyola/Hines VA-UCOP/Loyola University 1 Oregon Hlth Sci-UCOP/Oregon Hlth Sci Univ 4 LSU-New Orleans CCOP 1 Sutter Hlth Western/Davis, U of CA 4 Michael Reese Hosp/Oklahoma, Univ of 1 Wichita CCOP 4 Ohio State U 1 Cleveland Clin-UCOP/Cleveland Clinic OH 3 Ozarks Reg CCOP 1 Davis, U of CA-UCOP/Davis, U of CA 3 PSOC UCOP/Puget Sound 1 Colorado, U of-UCOP/Colorado, U of 2 Shadyside Hospital/Ohio State U 1 Henry Ford-UCOP/Henry Ford Hosp 2 Texas Tech Univ/San Antonio, U of TX 1 Oklahoma, U of -UCOP/Oklahoma, Univ of 2 Utah, U of - UCOP/Utah, U of 1 San Antonio, TX-UCOP/San Antonio, U of TX 2 Virginia Mason UCOP/Virginia Mason CCOP 1 BAMC/WHMC-UCOP/BAMC/WHMC 1 Total (27 Institutions) 58


S9916/III

S9916 Phase III Intergroup Coordinating Group: SWOG

Estramustine and Docetaxel Versus Mitoxantrone and Prednisone for Advanced, Hormone Refractory Prostate Cancer

Participants: SWOG, CALGB (99808), NCCTG, EMMES, CTSU

Study Coordinators: D Petrylak, J Jones, M Hussain, D Berry, P Burch (NCCTG), M Tapin (CALGB)




Schema

RANDOMIZATI

ON

Mitoxantrone +Prednisone

Docetaxel +Estramustine

Objectives To compare overall survival and progression-free survival in patients with hormone refractory me-tastatic prostate cancer Stage D1 or D2 random-ized to either estramustine and docetaxel or mi-toxantrone and prednisone.

To compare qualitative and quantitative toxicity between the two study arms.

To evaluate elements of quality of life, including: a) palliation of metastatic bone pain; and b) global quality of life.

To record PSA values for future correlations with response and survival.

To compare responses between the two treatment groups in patients with bidimensionally measur-able disease.

Patient Population Patients must have a histologic diagnosis of ade-nocarcinoma of the prostate which is measurable or evaluable Stage D1 or D2 that is unresponsive or refractory to hormone therapy. Patients with a history of brain metastases or who currently have brain metastases are not eligible.

Patients must have received prior hormonal ther-apy (refer to protocol for details). Prior radiation therapy (to less than 30% of the bone marrow only) and only one prior systemic therapy are al-lowed if at least four weeks have elapsed since completion of therapy. No prior strontium is al-lowed. Patients must not have had prior therapy with taxanes, mitoxantrone, estramustine or an-thracyclines. Patients may have received prior surgery if at least three weeks have elapsed since completion of surgery. Patients must have stopped bisphosphonates at least 28 days prior to


S9916/III

registration, and there must be no plans to receive concomitant bisphosphonates.

Patients must have a SWOG performance status of 0-2. Those with a performance status of 3 are allowed if the higher status is due to bone pain. Patients must have adequate renal and cardiac function. Patients with active thrombophlebitis or hypercoagulability, a known history of pulmo-nary embolus, or third space fluid accumulation are not eligible. Patients receiving anticoagulation therapy (excluding aspirin) prior to registration are not eligible except when it was used as pro-phylaxis against agents that might produce blood clots.

All patients must be offered the tissue correlative studies outlined in Section 15.4 of the protocol, and SWOG patients must be offered participation in the serum repository study, S9205.

Stratification/Descriptive Factors Patients will be stratified according to the follow-ing factors: (1) type of progression: progression of measurable or evaluable disease vs increasing PSA only; (2) NCI CTC "Pain" scale (as it relates to bone pain): Grade ≥ 2 vs < 2; and (3) SWOG performance status 0-1 vs 2-3.

Accrual Goals The accrual goal for this study is 620 eligible pa-tients. Two interim analyses will be performed when half of the patients are accrued to the study and when accrual is completed.

Summary Statement As of June 30, 2002, 638 patients have been reg-istered to this study. The study enrollment is av-eraging approximately 20 patients per month. Of the 120 ineligible patients, 53 (44%) are poten-tially reversible if required materials are submit-ted.

There have been eight major protocol deviations. Five patients on the D+E arm and two patients on

the M+P arm received no protocol treatment and are not assessable for toxicity. An additional pa-tient (not a deviation) received minimal protocol treatment and was not assessed for toxicity (M+P arm). The eighth major deviation was a patient who received intermittent RT while receiving protocol treatment (M+P arm).

Four hundred forty-six patients have been as-sessed for toxicity. Six patients experienced Grade 5 toxicities on the D+E arm for which ADRs were filed. One was filed because death occurred within 30 days of receiving treatment and is still being reviewed. A second patient died of GI bleeding where aspirin was thought to be contributory, the third patient died due to sepsis from necrotic prostate tissue and was probably treatment-related, a fourth died within a week of starting treatment (liver and renal failure, atrial fibrillation and pulmonary edema) and was possi-bly treatment-related per the Executive Officer, a fifth patient died from granulocytopenia and neu-tropenia and is under review, and the sixth death was a respiratory infection which is also under review. Three patients experienced a Grade 5 tox-icity on the M+P arm. One was a death within 30 days of treatment and another died of a respira-tory infection. The third patient died from dysp-nea with Grade 4 anorexia and respiratory infec-tion. These three ADR cases are under review. Thirty-nine other patients on the D+E arm and 21 additional patients on the M+P arm experienced Grade 4 toxicities.

The McGill Pain Questionnaire submission rates for this study are as follows: prestudy, 94%; Cy-cle 2, 77%; Cycle 3, 74%; and Cycle 4, 71%.

Based on the current rate of ineligibility, this study will accrue approximately 730 patients in order to obtain 620 eligible patients. Institutions are strongly urged to submit all outstanding data.


S9916/III

Initial Registrations By 3 Month Intervals

0

10

20

30

40

50

60

70

80

90


OCTDEC1999

1JANMAR2000

25

29

APRJUN2000

29

59

JULSEP2000

34

19

OCTDEC2000

43

21

JANMAR2001

37

35

APRJUN2001

30

29

JULSEP2001

21

23

OCTDEC2001

39

41

JANMAR2002

34

30

APRJUN2002

25

34

Docetaxel + Estramustine Mitoxantrone + Prednisone



Total Reg

CALGB 130 Mississippi, U of 9

NCCTG 59 Wichita CCOP 9 Davis, U of CA-UCOP/Davis, U of CA 32 Kansas, U of 8 EPP 32 Columbia River CCOP 7 Arkansas, U of-UCOP/Arkansas, U of 28 E Virginia UCOP 7 Southeast CCC CCOP 17 Kaiser Foundatn Hosp/Davis, U of CA 7 Columbia-Presby UCOP 16 William Beau Hosp/Michigan, U of 7 Oregon Hlth Sci-UCOP/Oregon Hlth Sci Univ 14 BAMC/WHMC-UCOP/BAMC/WHMC 6 Columbus CCOP 13 CTSU 5 Atlanta Reg CCOP 12 E Idaho Reg Med Ctr/Utah, U of 5 Utah, U of - UCOP/Utah, U of 12 Baylor College-UCOP 4 Greenville CCOP 11 Loyola/Hines VA-UCOP/Loyola University 4 Henrico Doctors Hosp/Galveston, U of TX 10 LSU-New Orleans CCOP 4 PSOC UCOP/Puget Sound 10 LSU-Shreveport UCOP/LSU-Shreveport 4 So Calif, U of-UCOP/So Calif, U of 10 Virginia Mason UCOP/Virginia Mason CCOP 4 Central IL CCOP 9 All Other Institutions 124 Dayton CCOP 9 Total (103 Institutions) 638


S9916/III

Registration, Eligibility, and Evaluability Registrations ending June 30, 2002; Data as of July 16, 2002

TOTAL Docetaxel +

Estramustine Mitoxantrone + Prednisone

NUMBER REGISTERED 638 317 321

INELIGIBLE 120 55 65 Insufficient Documentation 71 35 36 Irreversible 18 11 7 Reversible 53 24 29 ELIG./ PEND. ELIG. 518 262 256 Analyzable, Pend. Elig. 48 21 27 BASELINE DISEASE STATUS Measurable 127 67 60 Non Measurable 330 170 160 Too Early 61 25 36 RESPONSE ASSESSMENT Determinable 282 140 142 Not Determinable 70 39 31 Too Early 166 83 83 TOXICITY ASSESSMENT Evaluable 446 229 217 Not Evaluable 8 5 3 Too Early 64 28 36

Patient Characteristics Registrations ending June 30, 2002; Data as of July 16, 2002

Docetaxel + Estramustine

(n=262) Mitoxantrone + Prednisone

(n=256) AGE Median

70 .0

70 .0


215

82%

206

80%

Black (Non-Hispanic) 24 9% 34 13% Hispanic 19 7% 14 5% Asian 3 1% 2 1% Unknown 1 0% 0 0% TYPE OF PROGRESSION Measurable/Evaluable

211

81%

211

82%

PSA Only 51 19% 45 18% BONE PAIN ≥ Grade 2

95

36%

98

38%

< Grade 2 167 64% 158 62% PERFORMANCE STATUS 0-1

239

91%

224

88%

2-3 23 9% 32 13%


S9916/III

Treatment Summary Registrations ending June 30, 2002; Data as of July 16, 2002

TOTAL Docetaxel +

Estramustine Mitoxantrone + Prednisone

NUMBER ON PROTOCOL TREATMENT 126 70 56

NUMBER OFF PROTOCOL TREATMENT 392 192 200 REASON OFF TREATMENT Toxicity or side effects 47 33 14 Refusal unrelated to toxicity 15 10 5 Other - not protocol specified 35 13 22 Reason under review 15 5 10 MAJOR PROTOCOL DEVIATIONS 8 5 3

Number of Patients with a Given Type and Degree of Toxicity Toxicities with No Entries for Grades 3 to 5 Have Been Suppressed


Docetaxel + Estramustine Mitoxantrone

+ Prednisone (n=229) (n=217)

Grade Grade

TOXICITY ≤ 2 3 4 5 ≤ 2 3 4 5 ADR 228 0 0 1 216 0 0 1 Cardiovascular 204 16 8 1 203 10 4 0 Clotting 227 2 0 0 217 0 0 0 Flu-like Symptoms 211 16 2 0 206 11 0 0 Gastrointestinal 185 41 3 0 203 13 1 0 Hematologic 182 13 33 1 188 11 18 0 Hemorrhage 218 8 2 1 213 4 0 0 Immunological 227 2 0 0 217 0 0 0 Infection 203 23 1 2 202 12 2 1 Liver 223 5 0 1 209 8 0 0 Lung 220 6 2 1 212 3 1 1 Metabolic 216 12 1 0 216 1 0 0 Musculoskeletal 226 3 0 0 217 0 0 0 Neurologic 215 13 1 0 214 3 0 0 Pain 206 22 1 0 208 9 0 0 Renal/Bladder 224 4 0 1 215 2 0 0 MAXIMUM GRADE ANY TOXICITY Number

111 73 39 6

149 44 21 3


S9917/III


L-Selenium-Based Chemoprevention of Prostate Cancer Among Men with High Grade Prostatic Intraepithelial Neoplasia

Intergroup Participants: SWOG, CALGB, ECOG

Study Coordinators: J Marshall, W Sakr, D Wood, W Lee (CALGB), D Jarrad (ECOG)

Statisticians: C Tangen, D Pauler, J Faulkner

Data Coordinator: L Pruski-Clark


Schema

REGISTRATI

ON

Cancer

REPEAT

BI

OPSY*

HGPIN

RANDOMIZATI

ON

L-Selenomethionine

Placebo

Biopsy ProvenDiagnosis ofHGPIN

Normal

Exclude

*sextant or greater is recommended

(double-blinded)

Objectives To compare the effects of oral l-selenomethionine and placebo administered under randomized, double-blind conditions upon the three-year inci-dence rate of prostate cancer among men diag-nosed with high-grade prostatic intraepithelial neoplasia (HGPIN) and who have not been found to have prostate cancer in two sequential prostatic biopsies.

To compare the effects of oral l-selenomethionine and placebo upon the following: (1) prostatic cel-lular proliferation as measured by Ki67 immu-nostaining of prostatic biopsy slides, (2) prostatic cellular apoptosis as measured by TUNEL immu-

nohistochemistry of prostatic biopsy slides, and (3) degradation of basal cell integrity of prostate ducts, (4) changes in nuclear chromatin patterns as measured by machine-vision histometry, (5) rate of increase in PSA, and (6) symptoms of se-lenium toxicity.

Patient Population Patients must have had a digital rectal exam and biopsy of the prostate guided by TRUS within two years prior to initial registration that docu-ments HGPIN with no evidence of cancer. Pa-tients must agree to have this initial biopsy re-viewed and specimens submitted per protocol.


S9917/III

Patients must agree to stop taking dietary sup-plements which contain 50 mcg or more of sele-nium within 30 days prior to registration. The pa-tient must not be taking finasteride or any other androgen suppressor.

Patients must be at least 40 years old, and they must have an AUA symptom score of less that 20 as determined by the Participant Report of Symp-toms. Patients must have a SWOG performance status of 0 or 1, and they must have a PSA ≤ 10 ng/ml within three months prior to initial registra-tion.

For the randomization step, central SWOG pa-thology review must have confirmed the presence of HGPIN in the initial biopsy submitted at regis-tration. A second biopsy (sextant or greater is recommended) must also have been performed within three months prior to randomization, and local pathology review must have confirmed that there was no evidence of cancer present. No more than six months must have elapsed from initial registration to randomization.

Stratification/Descriptive Factors For randomization, patients will be stratified by the following factors: (1) age: 40-60 vs 61 or older; (2) race: African American vs other; (3) prestudy PSA: < 4 ng/ml vs 4-10 ng/ml; and (4) vitamin E supplementation: yes vs no.

Cancer Control Credits The NCI Division of Cancer Prevention has as-signed 1.0 cancer control credit to the first year of this study and 0.3 credit for each subsequent year.

Accrual Goals The accrual goal for this study is to randomize 466 eligible patients.

Summary Statement As of June 30, 2002, 163 patients have been reg-istered to this study. Recently, this study has been averaging eight registrations per month, and the anticipated accrual rate was 40 patients per month. Twenty-eight patients (17%) are ineligible due to insufficient or no pathology material sub-mitted (7), central pathology review could not confirm a diagnosis of HGPIN (8), inadequate or missing clinical eligibility documentation (11), and a baseline PSA > 10 ng/ml (2).

Eighty-seven eligible or review pending patients have gone on to be randomized. Thirty-nine are evaluable for toxicity with no Grade 3 or higher toxicity being observed. One patient refused study supplement after randomization and is not assessable for toxicity. He is coded as having a major deviation. Another major deviation is coded for a patient who received the incorrect supplement bottle for a period of time.

CALGB and ECOG joined this study on June 15, 2001 and December 12, 2001, respectively. Each has contributed three patients. Sixteen patients from the PCPT have been registered to this study.


S9917/III


0

10

20

30

40


APRJUN2000

2

JULSEP2000

4

OCTDEC2000

12

JANMAR2001

14

APRJUN2001

28

JULSEP2001

21

OCTDEC2001

26

JANMAR2002

34

APRJUN2002

22

Repeat Biopsy

Registration by Institution Initial Registration



Total Reg

Henry Ford-UCOP/Henry Ford Hosp 21 William Beau Hosp/Michigan, U of 3

Wayne State U-UCOP/Wayne State Univ 20 Bay Medical Center/Michigan, U of 2 BAMC/WHMC-UCOP/BAMC/WHMC 12 Baylor College-UCOP 2 Grand Rapids CCOP 11 Greenville CCOP 2 E Virginia UCOP 8 MD Anderson 2 Oklahoma, U of -UCOP/Oklahoma, Univ of 8 Valley Hospital/Columbia University 2 Cleveland Clin-UCOP/Cleveland Clinic OH 6 Virginia Mason UCOP/Virginia Mason CCOP 2 San Antonio, TX-UCOP/San Antonio, U of TX 6 City of Hope Med Ctr 1 Atlanta Reg CCOP 5 Columbia-Presby UCOP 1 Columbus CCOP 5 Greater Phoenix CCOP 1 Central IL CCOP 4 Hawaii CCOP, Univ of 1 Akron Gen Med Ctr/Cleveland Clinic OH 3 Los Angeles, U of CA 1 Arizona, U of-UCOP/Arizona, U of 3 Loyola/Hines VA-UCOP/Loyola University 1 CALGB 3 Michigan, U of-UCOP 1 Colorado, U of-UCOP/Colorado, U of 3 Mississippi, U of 1 Columbia River CCOP 3 New Mexico MBCCOP 1 ECOG 3 Our Lady, Bellefonte/Cleveland Clinic OH 1 Muskogee Reg Med Ctr/Oklahoma, Univ of 3 PSOC UCOP/Puget Sound 1 Oregon Hlth Sci-UCOP/Oregon Hlth Sci Univ 3 Santa Rosa CCOP 1 Upstate Carolina 3 Total (40 Institutions) 163 Wichita CCOP 3


S9917/III

Registration, Eligibility, and Evaluability Initial Registration


Repeat Biopsy Repeat Biopsy NUMBER REGISTERED 163 ELIG./ PEND. ELIG. 135

INELIGIBLE 28 Analyzable, Pend. Elig. 63 Insufficient Documentation 16 Irreversible 5 Reversible 11

Registration by Institution Randomization



Total Reg

Henry Ford-UCOP/Henry Ford Hosp 14 Wichita CCOP 2

Wayne State U-UCOP/Wayne State Univ 13 William Beau Hosp/Michigan, U of 2 Grand Rapids CCOP 10 Bay Medical Center/Michigan, U of 1 BAMC/WHMC-UCOP/BAMC/WHMC 7 Baylor College-UCOP 1 Cleveland Clin-UCOP/Cleveland Clinic OH 5 Colorado, U of-UCOP/Colorado, U of 1 Atlanta Reg CCOP 4 Columbia-Presby UCOP 1 Oklahoma, U of -UCOP/Oklahoma, Univ of 4 Greater Phoenix CCOP 1 San Antonio, TX-UCOP/San Antonio, U of TX 4 Los Angeles, U of CA 1 Arizona, U of-UCOP/Arizona, U of 3 Michigan, U of-UCOP 1 Central IL CCOP 3 Mississippi, U of 1 Columbia River CCOP 3 New Mexico MBCCOP 1 Columbus CCOP 3 Oregon Hlth Sci-UCOP/Oregon Hlth Sci Univ 1 E Virginia UCOP 3 Our Lady, Bellefonte/Cleveland Clinic OH 1 Akron Gen Med Ctr/Cleveland Clinic OH 2 PSOC UCOP/Puget Sound 1 CALGB 2 Santa Rosa CCOP 1 ECOG 2 Valley Hospital/Columbia University 1 Greenville CCOP 2 Virginia Mason UCOP/Virginia Mason CCOP 1 Muskogee Reg Med Ctr/Oklahoma, Univ of 2 Total (36 Institutions) 107 Upstate Carolina 2

Registration, Eligibility, and Evaluability Randomization


TOTAL X Y NUMBER REGISTERED 107 52 55

INELIGIBLE 20 13 7 Insufficient Documentation 16 11 5 Irreversible 3 1 2 Reversible 13 10 3 ELIG./ PEND. ELIG. 87 39 48 Analyzable, Pend. Elig. 35 12 23 TOXICITY ASSESSMENT Evaluable 39 17 22 Not Evaluable 1 1 0 Too Early 47 21 26


S9917/III

Patient Characteristics Randomization


X

(n=39) Y

(n=48) AGE 40-60

12

15

61 or older 27 33 RACE African American

5

13%

10

21%

Other 34 87% 38 79% BASELINE PSA < 4 ng/ml

19

49%

17

35%

4-10 ng/ml 20 51% 31 65% VITAMIN E SUPPLEMENTATION Yes

18

46%

14

29%

No 21 54% 34 71%

Treatment Summary Randomization


TOTAL X Y NUMBER ON PROTOCOL TREATMENT 82 36 46

NUMBER OFF PROTOCOL TREATMENT 5 3 2 REASON OFF TREATMENT Treatment completed as planned 0 0 0 Toxicity or side effects 1 1 0 Refusal unrelated to toxicity 2 1 1 Other - not protocol specified 1 1 0 Reason under review 1 0 1 MAJOR PROTOCOL DEVIATIONS 2 1 1


S9917/III

Number of Patients with a Given Type and Degree of Toxicity Randomization


X Y (n=17) (n=22)

Grade Grade

TOXICITY 0 1 2 3 4 5 0 1 2 3 4 5 Diarrhea without colostomy 17 0 0 0 0 0 21 1 0 0 0 0 Edema 16 0 1 0 0 0 22 0 0 0 0 0 Fatigue/malaise/lethargy 17 0 0 0 0 0 20 2 0 0 0 0 Flatulence 16 1 0 0 0 0 22 0 0 0 0 0 Headache 16 1 0 0 0 0 22 0 0 0 0 0 Hematuria 16 0 1 0 0 0 22 0 0 0 0 0 Hypertension 17 0 0 0 0 0 21 1 0 0 0 0 Nausea 16 1 0 0 0 0 22 0 0 0 0 0 Urinary frequency/urgency 17 0 0 0 0 0 21 1 0 0 0 0 MAXIMUM GRADE ANY TOXICITY Number

13 2 2 0 0 0

19 3 0 0 0 0


S9921/III


Adjuvant Androgen Deprivation Versus Mitoxantrone Plus Prednisone Plus Androgen Deprivation in Selected High Risk Prostate Cancer in Patients

Following Radical Prostatectomy

Participants: SWOG, CALGB (99904), EMMES, CTSU

Study Coordinators: M Glode, M Hussain, G Swanson, D Wood, W Sakr, N Dawson (CALGB), N Belzer-Haas (ECOG)




Schema

RANDOMIZATI

ON

Mitoxantrone + Prednisone + Casodex + Zoladex

Casodex + Zoladex

Objectives The primary objective is to evaluate overall sur-vival using adjuvant systemic therapy in high risk localized prostate cancer patients following radi-cal prostatectomy. Disease-free survival will also be evaluated.

To compare qualitative and quantitative toxicity between the two study arms.

Patient Population Patients must have a histologic diagnosis of clini-cal Stage T1-T2 adenocarcinoma of the prostate prior to radical prostatectomy. Patients must have had a radical prostatectomy within 120 days prior to registration and must fulfill one or more of the following: (a) pathologic Gleason sum ≥ 8, (b)

pT3b (seminal vesical) or pT4 or N1, (c) patho-logical Gleason sum equal to 7 and positive mar-gin, or (d) patients who have either a preoperative serum PSA value > 15 ng/ml, or a biopsy Gleason score > 7, or both a serum PSA level > 10 ng/ml and a biopsy Gleason score > 6 are also eligible. Patients must not have confirmed distant metas-tatic disease. Patients must have an undetectable post-operative serum PSA (≤ 0.2 ng/ml). Patients with PSA at clinical diagnosis ≥ 20 ng/ml must have a bone scan not suggestive of metastatic dis-ease.

Patients may have had prior neoadjuvant hormo-nal therapy of ≤ 4 months duration prior to radi-cal prostatectomy provided that the patients ful-filled the clinical eligibility criteria prior to hor-


S9921/III

monal treatment. Low dose megace for the treat-ment of hot flashes is permitted. No other prior therapy is allowed.

Patients must have adequate cardiac function and a SWOG performance status of 0 or 1. Patients must have serum testosterone level measured within 28 days prior to registration.

Stratification/Descriptive Factors Patients will be stratified by the following fac-tors: (1) surgical extent of disease: organ con-fined vs not organ confined but N0 vs N1; (2) Gleason's sum: <7 vs 7 vs >7; and (3) Radiation Therapy planned: yes vs no.

Accrual Goals The accrual goal for this study is 1,360 eligible patients. Three interim analyses will be per-formed when approximately 1,000 patients are

accrued to the study, after 50% of the expected deaths (275 deaths) have occurred, and 2.5 years after accrual has been completed.

Summary Statement As of June 30, 2002, 175 patients had been regis-tered to this study. It was projected that 20 pa-tients per month would be randomized, over the last three months the average has been 15 patients per month. Seven patients are ineligible; all are potentially reversible. Thirty-seven patients are assessable for toxicity. There have been no Grade 4 toxicities reported. Four patients who refused protocol treatment are not assessable for toxicity, and are coded as having a major deviation.

ECOG formally endorsed this study through the CTSU as of January 15, 2002.


0

10

20


FEB2000

1

1

MAY2000

1

1

JUN2000

2

JUL2000

2

OCT2000

1

3

NOV2000

7

1

DEC2000

1

1

JAN2001

4

2

FEB2001

3

3

MAR2001

5

6

APR2001

3

4

MAY2001

4

4

JUN2001

1

3

JUL2001

3

3

AUG2001

2

2

SEP2001

2

4

OCT2001

2

4

NOV2001

8

2

DEC2001

3

5

JAN2002

6

6

FEB2002

4

3

MAR2002

4

4

APR2002

7

6

MAY2002

10

9

JUN2002

5

7

Casodex + Zoladex Mitox + Pred + Caso + Zoladex


S9921/III



Total Reg

CALGB 28 PSOC UCOP/Puget Sound 2

Wayne State U-UCOP/Wayne State Univ 24 Rochester, Univ of 2 Colorado, U of-UCOP/Colorado, U of 14 San Antonio, TX-UCOP/San Antonio, U of TX 2 Arkansas, U of-UCOP/Arkansas, U of 11 Southeast CCC CCOP 2 Columbia-Presby UCOP 11 Wichita CCOP 2 So Calif, U of-UCOP/So Calif, U of 9 Atlanta Reg CCOP 1 Loyola/Hines VA-UCOP/Loyola University 8 Boulder Comm Hosp/Colorado, U of 1 Tulane U - UCOP/Tulane University 7 Greater Phoenix CCOP 1 Davis, U of CA-UCOP/Davis, U of CA 4 Keesler USAF Med Ctr/Mississippi, U of 1 City of Hope Med Ctr 3 LSU-Shreveport UCOP/LSU-Shreveport 1 Grand Rapids CCOP 3 MedStar Onc Network/Davis, U of CA 1 Mississippi, U of 3 Mem Hosp, Co Springs/Colorado, U of 1 Oklahoma, U of -UCOP/Oklahoma, Univ of 3 Michigan, U of 1 William Beau Hosp/Michigan, U of 3 Michigan, U of-UCOP 1 BAMC/WHMC-UCOP/BAMC/WHMC 2 Montana CCOP 1 Baylor College-UCOP 2 Our Lady of Lourdes/LSU-Shreveport 1 Cleveland Clin-UCOP/Cleveland Clinic OH 2 Providence Hosp 1 E Virginia UCOP 2 Sutter Hlth Western/Davis, U of CA 1 EPP 2 Thibodaux Hospital/Tulane University 1 Kansas, U of 2 Upstate Carolina 1 Kentucky, U of-UCOP/Kentucky, U of 2 Virginia Mason UCOP/Virginia Mason CCOP 1 Madigan Army Med Ctr/Puget Sound 2 Total (44 Institutions) 175 Oregon Hlth Sci-UCOP/Oregon Hlth Sci Univ 2


TOTAL Casodex

+ Zoladex

Mitox + Pred + Caso

+ Zoladex NUMBER REGISTERED 175 87 88

INELIGIBLE 7 2 5 Insufficient Documentation 7 2 5 Reversible 7 2 5 ELIG./ PEND. ELIG. 168 85 83 Analyzable, Pend. Elig. 124 61 63 TOXICITY ASSESSMENT Evaluable 37 19 18 Not Evaluable 4 1 3 Too Early 127 65 62


S9921/III


Casodex + Zoladex

(n=85)

Mitox + Pred + Caso + Zoladex (n=83)

AGE Median

59 .0

59 .0


66

78%

60

72%

Black (Non-Hispanic) 15 18% 13 16% Hispanic 4 5% 6 7% Asian 0 0% 4 5% EXTENT OF DISEASE Organ Confined

24

28%

23

28%

Not Organ Confined, but N0 46 54% 45 54% N1 15 18% 15 18% GLEASON SCORE <7

7

8%

4

5%

7 39 46% 41 49% >7 39 46% 38 46% RADIATION THERAPY PLANNED Yes

16

19%

14

17%

No 69 81% 69 83%

Treatment Summary Registrations ending June 30, 2002; Data as of July 19, 2002

TOTAL Casodex

+ Zoladex

Mitox + Pred + Caso

+ Zoladex NUMBER ON PROTOCOL TREATMENT 151 81 70

NUMBER OFF PROTOCOL TREATMENT 17 4 13 REASON OFF TREATMENT Treatment completed as planned 1 0 1 Toxicity or side effects 2 0 2 Refusal unrelated to toxicity 4 2 2 Other - not protocol specified 3 1 2 Reason under review 7 1 6 MAJOR PROTOCOL DEVIATIONS 4 1 3


S9921/III

Number of Patients with a Given Type and Degree of Toxicity Toxicities with No Entries for Grades 2 to 5 Have Been Suppressed


Casodex + Zoladex Mitox + Pred + Caso + Zoladex

(n=19) (n=18)

Grade Grade

TOXICITY Unk 0 1 2 3 4 5 Unk 0 1 2 3 4 5 Abdominal pain/cramping 0 18 1 0 0 0 0 0 17 0 1 0 0 0 Anxiety/agitation 0 16 1 1 1 0 0 0 18 0 0 0 0 0 Arthralgia 0 19 0 0 0 0 0 0 17 0 0 1 0 0 Bone pain 0 19 0 0 0 0 0 0 17 0 1 0 0 0 Erectile impotence 0 18 0 0 1 0 0 0 16 0 1 1 0 0 Fatigue/malaise/lethargy 0 17 2 0 0 0 0 0 11 6 1 0 0 0 Fever, NOS 0 19 0 0 0 0 0 0 17 0 1 0 0 0 Hot flashes 1 8 6 4 0 0 0 0 4 6 7 1 0 0 Hyperglycemia 0 18 0 1 0 0 0 0 18 0 0 0 0 0 Hypertension 0 19 0 0 0 0 0 0 16 1 0 1 0 0 Incontinence 1 17 0 1 0 0 0 0 17 0 1 0 0 0 Leukopenia 0 18 1 0 0 0 0 0 16 0 1 1 0 0 Libido loss 0 18 0 1 0 0 0 0 17 0 1 0 0 0 Lymphopenia 0 19 0 0 0 0 0 0 13 0 4 1 0 0 Male infertility 0 19 0 0 0 0 0 0 17 0 0 1 0 0 Myalgia 0 19 0 0 0 0 0 0 17 0 0 1 0 0 Nail changes 0 19 0 0 0 0 0 0 17 0 1 0 0 0 Neutropenia/granulocytopenia 0 19 0 0 0 0 0 0 11 4 1 2 0 0 Pain-other 0 19 0 0 0 0 0 0 17 0 1 0 0 0 Sensory neuropathy 0 19 0 0 0 0 0 0 16 1 0 1 0 0 Stomatitis/pharyngitis 0 18 1 0 0 0 0 0 17 0 1 0 0 0 Sweating 1 18 0 0 0 0 0 0 15 2 1 0 0 0 Weight gain 0 18 0 1 0 0 0 0 16 2 0 0 0 0 MAXIMUM GRADE ANY TOXICITY Number

1 7 5 4 2 0 0

0 1 4 6 7 0 0


S0000/III


Selenium and Vitamin E Cancer Prevention Trial (SELECT)

Intergroup Participants: SWOG, CALGB, CUOG, ECOG, NCCTG, RTOG, VACSP

Study Coordinators: S Lippman, E Klein, I Thompson, L Klotz (CUOG), D Karp (ECOG), M Lieber (NCCTG), F Khuri (RTOG), M Gaziano (VACSP), P Walther (CALGB)

Statisticians: P Goodman, A Darke, T Chay, K Gower, C Tangen, J Crowley

Project Manager: J Hartline

Data Coordinators: M Yee, D Marrah, J McNurlin, M Scott, J Farrell


Schema

Eligibility Assessment

INITIAL

VISIT

RANDOMIZATION*

Vitamin E + Selenium

Vitamin E + Placebo

Placebo + Placebo

28-90 Days

* Randomization will be double-blind

Placebo + Selenium

Objectives To assess the effect of selenium and vitamin E alone and in combination on the clinical inci-dence of prostate cancer.

To assess the effect of selenium and vitamin E alone and in combination on the incidence of other cancers including lung, colorectal, and all cancers combined.

To assess the effect of selenium and vitamin E alone and in combination on prostate cancer-free survival, lung cancer-free survival, colorectal cancer-free survival, all cancer-free survival, overall survival, and serious cardiovascular events.

To assess the effect of selenium and vitamin E alone and in combination on Health Related


S0000/III

Quality of Life (HRQL) as measured by the Physical and Mental Health Component Scales of the SF-36V.

To evaluate the association of biological and mo-lecular markers with the risk of prostate cancer, lung cancer and colorectal cancer.

To explore the relationship between the effects of study supplements and prostate cancer risk and genetic factors.

To evaluate cellular and molecular markers from banked tissue on the biology of prostate carcino-genesis and study supplement effects.

To assess whether the effects of the study sup-plements on prostate cancer risk are conditional upon duration and dose of pre-randomization use of the study supplements.

To assess whether the effects of the study agents are conditional upon intakes of other nutrients, foods, and dietary supplements.

To assess the effect of other dietary nutrients and dietary patterns on prostate cancer risk.

Patient Population All participants must have a digital rectal exami-nation (DRE) deemed not suspicious for prostate cancer and a total PSA ≤ 4.0 ng/ml within 364 days prior to randomization. All individuals pre-viously diagnosed with prostate cancer or high grade (Grade 2-3) Prostatic Intraepithelial Neo-plasia (HGPIN) are ineligible.

Participants must be male and at least 55 years of age. African American men must be 50 years or older. Participants must not be taking (on the day of randomization) or planning to take any sup-plements or multivitamins containing any vitamin

E or selenium. Individuals receiving anticoagula-tion therapy are ineligible; aspirin (average daily dose ≤ 175 mg/day, ≤ 81 mg/day if also taking plavix) as prophylaxis is acceptable. Participants must not have a history of hemorrhagic stroke. Participants must have a systolic blood pressure < 160 mm/Hg and a diastolic blood pressure < 90 mm/Hg at the time of randomization.

Stratification/Descriptive Factors Randomizations will be balanced by permuted blocks within each Study Site.

Cancer Control Credits The NCI Division of Cancer Prevention (DCP) has assigned 1 cancer control credit per randomi-zation and 0.3 credits per year for each year of follow-up.

Accrual Goals A total of 32,400 men will be randomized to this study with a target African American population of 20%.

Summary Statement This study was opened on July 25, 2001. Ran-domizations have been brisk, averaging 955 men per month over the last three months. Over 370 Study Centers and Sites are actively randomizing participants. As of June 30, 2002, 12,586 subjects had been randomized.

Recruitment of minorities continues to be a chal-lenge. To date, approximately 11.5% of the ran-domized men are African American, some of whom are also Hispanic. Numerous activities to increase minority recruitment are ongoing, result-ing in a steady increase in the percent of minori-ties on the trial.


S0000/III

Randomizations by Monthly Intervals

0

500

1,000

1,500

2,000


AUG2001

152

SEP2001

906

OCT2001

1915

NOV2001

1816

DEC2001

1321

JAN2002

1396

FEB2002

1094

MAR2002

1121

APR2002

1087

MAY2002

952

JUN2002

826

Total


S0000/III

Randomizations by Study Center Registrations ending June 30, 2002


Total Reg

Vancouver Hospital 378 Oregon Hlth Sci Univ 70

San Diego, U of CA 319 Cedar Rapids CCOP 69 Swedish Medical Ctr 242 Atlanta Reg CCOP 66 London Reg Ca Ctr 241 San Juan MBCCOP 66 London HSC 239 Baylor Univ Med Ctr 64 Southeast CCC CCOP 234 Northwest CCOP 64 Altamira Family MC 213 Thompson Ca Surv Ctr 63 Pennsylvania/Univ of 213 Vermont Cancer Ctr 60 Baptist Hosp East 198 VAMC Dallas 59 Grand Rapids CCOP 195 St Luke's/Mt States 58 Northwest Hosp 178 Washington Univ 57 Central IL CCOP 172 Marshfield Clinic 56 LDS Hospital 171 Mount Sinai CCOP 56 Mayo - Rochester 165 Nebraska, Univ of 56 Upstate Carolina 158 Geisinger Clinic 55 Northwestern Univ 156 Memphis, U of TN 55 MD Anderson 154 Med Col of Virginia 54 Iowa Oncology CCOP 149 Princess Margaret 54 Mississippi, Univ of 146 VAMC Puget Sound 54 Illinois, Univ of 143 Miami, Univ of 52 Wichita CCOP 143 Stanford University 52 Arizona Cancer Ctr 142 Centro Clinico 51 Fox Chase Cancer Ctr 140 Colorado Ca Res Prog 51 Rush Presbyterian 138 Lionel B. Katchem 50 Mid Delta FP 126 SUNY Stony Brook 50 US Oncology 124 Stormont-Vail Health 49 Toledo CCOP 118 Berkshire Hem/Onc 48 Dayton CCOP 113 H Lee Moffitt Cancer 48 Sentara Cancer Inst 109 Sutter Hlth CRG-East 48 Sunnybrook & Women's 109 Camcare Health 47 VAMC Minneapolis 106 Christiana Care Hlth 47 Colorado, Univ of 105 Methodist, Dallas 46 Wisconsin, Univ of 105 Missouri Baptist MC 46 Lehigh Valley Hosp 103 Bay Area CCOP 45 Missouri Valley CCOP 103 Prostate Cancer Inst 44 Carle Cancer Center 102 Lahey Clinic Med Ctr 43 INTEGRIS Oncology 99 East Tennessee State 42 St Joseph Mercy Hosp 99 VAMC Kansas City 42 Centre de Recherche 98 Bassett Research Ins 40 Henry Ford Hosp 98 VAMC Hines 40 Metro-Minnesota CCOP 97 Columbia University 39 Southern Nevada CCOP 97 Kansas City CCOP 39 VAMC Houston 97 Syracuse CCOP 39 George Washington U 94 VAMC Northport 39 Northern Indiana CRC 92 Walter Reed AMC 39 Cascadia Clin Trials 91 Northern NJ CCOP 38 Sioux Community CC 87 Greater Phoenix CCOP 37 Baptist Med Ctr 85 San Antonio, U of TX 37 Iowa Hosp, Univ of 82 VAMC Louisville 37 VAMC Cleveland 82 VAMC Boston 36 MeritCare Hosp CCOP 81 City of Hope Med Ctr 35 Vanderbilt Univ 81 Gulf Coast MBCCOP 35 LSU-Shreveport 80 Our Lady, Bellefonte 35 Cleveland Clinic 79 Regional CC-Waukesha 35 Duluth CCOP 79 VAMC Jerry L. Pettis 35 Kalamazoo CCOP 79 Columbia River CCOP 34 William Beau Hosp 79 Glendale Mem Hosp 34 VAMC Phoenix 72 Harbor-UCLA 34 Wilford Hall Med Ctr 72 Howard University 34 Med Col of Wisconsin 71 Good Samaritan Hosp 33 Miguel Sosa Padilla 71 Huntington Mem Hosp 33


S0000/III

Randomizations by Study Center Registrations ending June 30, 2002


Total Reg

Kaiser Permanente-GA 33 NY Methodist Hosp 18

Maryland, Univ of 33 VAMC Greater LA 18 Michigan, Univ of 33 Roswell Park 17 Ozarks CCOP 33 Schiffler Cancer Ctr 17 Virginia Mason CCOP 33 VAMC Gainesville 17 VAMC Salisbury 32 Hawaii CCOP 16 Scott & White CCOP 31 UAB Div of Prev Med 16 Chicago Consortium 30 Los Angeles, U of CA 15 Connecticut, Univ of 30 Mayo - Scottsdale 15 Indiana University 30 Tulane University 15 Evanston Hospital 29 VAMC Fargo 14 Ireland Cancer Ctr 29 VAMC Durham 12 Downstate Med Ctr 28 VAMC James A. Haley 12 Loyola University 28 VAMC Providence 12 Santa Rosa CCOP 28 Galveston, U of TX 11 Columbus CCOP 27 North Shore CCOP 11 Lawrence & Mem Hosp 27 So Calif, U of 11 Ochsner CCOP 27 VAMC Central Texas 11 Oklahoma, Univ of 27 Harris Methodist 10 VAMC Pittsburgh 27 Mt Zion Cancer Ctr 10 VAMC Syracuse 27 N Idaho Cancer Ctr 10 Baptist Mem Hosp 26 Ottawa General Hosp 10 Kimmel Cancer Ctr 26 Summa Health System 10 LSU-New Orleans 26 VAMC Palo Alto 10 Queen Elizabeth HSC 25 Wayne State/Karmanos 10 VAMC Birmingham 24 Beth Israel Deacones 9 VAMC St Louis 24 St Francis Hospital 9 Main Line/Lankenau 23 Boston Medical Ctr 8 McGill University HC 23 Good Samaritan MC 8 Northwestern Ontario 23 VAMC Western NY 7 Rochester, Univ of 23 Irvine, Univ of CA 6 VAMC Long Beach 23 New Mexico, Univ of 6 VAMC So Arizona 23 WVU-Morgantown 6 Wake Forest Univ 23 Ohio State Univ 5 Anne Arundel Med Ctr 22 VAMC Asheville 5 Greenville CCOP 22 WNY Urology Assoc 4 Pittsburgh Ca Inst 22 Arkansas, Univ of 3 VAMC McGuire 22 Dartmouth Hitchcock 3 VAMC New Jersey 22 Johns Hopkins Univ 2 Cincinnati, Univ of 21 Long Beach Memorial 2 Montana CCOP 21 Central PA Hem & Med 1 Texas Tech Univ 21 Maine General MC 1 Regional Cancer Ctr 20 Providence Hosp 1 Tyler, U of TX 19 Valley Hospital 1 VAMC Leavenworth 19 VAMC Lebanon 1 VAMC Stratton 19 VAMC Oklahoma City 1 VAMC Washington DC 19 Total (215 DM Institutions) 12,586


S0000/III

Participant Characteristics All eligible and selected ineligible patients included


Total

(n=12586) Total

(n=12586)

AGE CCOP Median 62 .0 Yes 3,529 28% Minimum 50 No 9,057 72% Maximum 93 COOPERATIVE GROUP AGE GROUP SWOG 4,072 32% 50 - 54 years 473 4% ECOG 2,212 18% 55 - 64 years 7,422 59% CALGB 1,406 11% 65 - 74 years 3,916 31% RTOG 274 2% 75+ years 775 6% NCCTG 1,073 9% CUOG 716 6% PREVIOUS PCPT PARTICIPANT VACSP 1,033 8% Yes 691 5% WHI 601 5% No 11,895 95% ALLHAT 544 4% NONE 655 5% RACE White 10,498 83% VA African American 1,297 10% Yes 1,216 10% Hispanic (Non-Afri.American) 527 4% No 11,370 90% Hispanic (Afri. American) 119 1% Aboriginal 22 0% Asian/Pacific Islander 115 1% Unknown 8 0%


S0000A/III

S0000A Phase III Intergroup

Prevention of Alzheimer's Disease with Vitamin E and Selenium (PREADVISE)

Intergroup Participants: SWOG, CALGB, CUOG, ECOG, NCCTG, RTOG, VACSP

Study Coordinators: W Markesbery, R Kryscio, F Schmitt

Statisticians: P Goodman, A Darke, T Chay, K Gower, C Tangen, J Crowley

Project Manager: J Hartline

Data Coordinators: M Yee, D Marrah, J McNurlin, M Scott, J Farrell


Schema

RANDOMIZETO SELECT

Evaluate cognitive eligibility

REGISTRATION

Objectives To define the effect of selenium and vitamin E in combination in the reduction of the incidence of Alzheimer�s disease (AD), as determined by mental status screening and clinical evaluation, in a population of men age 62 or older (60 if of Af-rican descent or Hispanic) participating in SE-LECT.

To define the effect of selenium and vitamin E alone in the reduction of the incidence of Alz-heimer�s disease (AD), as determined by mental status screening and clinical evaluation, in a population of men age 62 or older (60 if of Afri-can descent or Hispanic) participating in SE-LECT.

To assess the combined and individual effects of selenium and vitamin E in the reduction of the in-

cidence of other neurodegenerative diseases, in-cluding dementia with Lewy bodies, frontotem-poral dementia (including Pick's disease), corti-cobasal degeneration, progressive supranuclear palsy, and vascular dementia.

To evaluate the sensitivity and specificity of the Memory Impairment Screen (MIS) relative to the Consortium to Establish a Registry in AD (CERAD) mental status measures (in a subsample of 500 participants).

To study the features of normal cognitive aging (in a subsample of 200 participants) and to assess the effect of selenium and vitamin E on this proc-ess.


S0000A/III

To study the progression of AD and other neu-rodegenerative diseases in participants clinically diagnosed with AD or other dementia.

To evaluate the association of apoliprotein E (APOE) epsilon-4 alleles and other potential bio-logical molecular markers with the risk of Alz-heimer's disease and other neurodegenerative dis-eases in this population.

Patient Population The potential PREADVISE participant must be a SELECT participant (S0000). If his SELECT randomization visit occurs on or after June 1, 2002, he must be registered to PREADVISE at the same time that he is randomized to SELECT. Participants who were randomized to SELECT before June 1, 2002 may be registered to PREADVISE at their first Six Month SELECT Visit.

A baseline Memory Impairment Screen (MIS) must be administered prior (within 30 days) to enrollment in PREADVISE and the participant must score 5 or greater.

Participants must be age 62 or older at the time of SELECT randomization. Men of African or His-panic descent must be 60 or older at the time of SELECT randomization.

The participant must not have any of the follow-ing neurological conditions based on self-report (were told by a physician): Alzheimer's disease, or any other form of dementia such as Pick�s dis-

ease, dementia with Lewy bodies, frontotemporal dementia, vascular dementia, significant cogni-tive and motor impairment from a stroke or corti-cobasal degeneration, Huntington's disease, epi-lepsy, Parkinson's disease, brain tumor, multiple sclerosis, manic-depressive disorder, or schizo-phrenia. The participant must not have had a head injury with prolonged loss of consciousness (over 30 minutes) within the past five years. The par-ticipant must not have blindness, deafness, lan-guage difficulties or any other disability that may prevent completion of the MIS.

The participant must not have had an alcohol or substance abuse diagnosis in the past 24 months. The participant must not have had a diagnosis of depression or anxiety disorder in the past 4 months.

The participant must not currently use of any of the following medications: Aricept, Cognex, Ex-elon, Reminyl, or Hydergine.

Cancer Control Credits No cancer control credits will be given.

Accrual Goals A total of 10,560 men will be registered to this study.

Summary Statement This study was opened on May 17, 2002. As of June 30, 2002, 19 patients had been registered to this study.

Registration by DM Institution Registrations ending June 30, 2002

Institutions Total Reg

Missouri Valley CCOP 16

VAMC Louisville 2 Scott & White CCOP 1 Total (3 DM Institutions) 19


S0028/II

S0028 Phase II

Assessment of Gemcitabine and Paclitaxel for Metastatic Urothelial Cancer in Patients Aged 70 Years and Older

Study Coordinators: D Raghavan, C Gotay




Objectives To assess the feasibility of enrolling patients aged 70 years or older with advanced urothelial cancer to a structured Phase II trial including pharma-cokinetic sampling.

To assess the anticancer efficacy of the regimen of paclitaxel and gemcitabine for the management of advanced cancer of the bladder in patients aged 70 years and older, based on objective response rate (confirmed and unconfirmed complete and partial responses) and two year survival.

To estimate toxicity and tolerability of the regi-men in this specific population group.

To assess the feasibility of using standardized self-report measures of comorbidity, depression and functional status in an elderly population of patients with cancer.

To assess parameters of clinical pharmacology of paclitaxel and gemcitabine in patients aged 70 years and older, including half life value(s), AUC and steady state levels.

To assess whether patients under 60 years have clinical pharmacologic parameters similar to those reported in the literature (to validate our as-say system).

To explore, at a preliminary level, the feasibility of studying genetic polymorphisms in the expres-sion of deoxycytidine kinase, deoxycytidine deaminase, beta-tubulin gene mutations and mul-tidrug resistance functions in this elderly popula-tion.

Patient Population Patients must have a histologically confirmed di-agnosis of urothelial cancer (transitional cell car-cinoma, adenocarcinoma, or squamous carci-noma). Patients must have measurable disease that meets one of the following criteria: (1) previ-ously untreated metastatic or locoregionally ad-vanced disease (i.e., bulky pelvic nodes), (2) lo-cally recurrent carcinoma after radiotherapy (where further radiotherapy or cystectomy are not appropriate), or (3) locally recurrent carcinoma after cystectomy (where further surgery or radio-therapy are not appropriate).

Patients must have recovered from the effects of prior surgery or radiation. Patients must not have received prior chemotherapy for cancer.

Patients must be 70 years or older, or less than 60 years, and they must have a Zubrod performance status of 0-2. Patients known to be HIV positive are not eligible. Patients must have adequate re-nal, hepatic and hematologic function.

Stratification/Descriptive Factors Patients are stratified by age: < 60 years vs 70 years or older.

Accrual Goals Sixty patients aged 70 years or older will be ac-crued. In addition, 20 patients under age 60 will be accrued.

Summary Statement Seven patients were registered to this study as of June 30, 2002.

Note that funds are available for pharmacology sample processing, as described in section 15.1 of the study protocol.


S0028/II



PSOC UCOP/Puget Sound 2

BAMC/WHMC-UCOP/BAMC/WHMC 1 Davis, U of CA-UCOP/Davis, U of CA 1 Kansas City CCOP 1 Southeast CCC CCOP 1 St Mary's Hosp/St Louis University 1 Total (6 Institutions) 7


Paclitaxel/Gemcitabine

(n=7) Paclitaxel/Gemcitabine

(n=7)

AGE RACE Median 75 .0 White (Non-Hispanic) 7 100% Minimum 37 Maximum 81 AGE ≥ 70 years 6 SEX < 60 years 1 Males 4 57% Females 3 43%


S0031/II

S0031 Phase II

Evaluation of ZD 1839 for Advanced Transitional Cell Carcinoma of the Urothelium

Study Coordinators: D Petrylak, P Van Veldhuizen




Date Closed (Temporary): 6/1/2002

Objectives To assess the 6-month progression-free survival of patients with advanced urothelial cancer treated with ZD 1839 who have previously failed one prior systemic chemotherapy regimen.

To assess the overall survival and response rate (confirmed complete and partial response) in this group of patients.

To evaluate the qualitative and quantitative tox-icities of this regimen.

To investigate in a preliminary manner the changes in growth factor protein kinase expres-sion pre and post treatment and at the time of dis-ease progression.

Patient Population Patients must have a histologically confirmed Stage M1 transitional cell carcinoma (TCC) of the urothelial tract (bladder, renal pelvis, ureter, and urethra) which is not curable by surgery or radiation therapy. Stage N+, M0 patients with un-resectable disease are also eligible. Patients with adenocarcinoma, small cell carcinoma, sarcomas or squamous cell carcinoma or mixed adeno/squamous/transitional histology are not eligible. Poorly differentiated TCC, or predomi-nant TCC with rare foci of squamous differentia-tion or rare foci of adenocarcinoma are allowed. Patients must have measurable disease. Patients must have disease that has progressed or recurred following one prior systemic chemotherapy regi-men for advanced disease.

Patients may have had prior intravesical therapy, radiation therapy, or surgery with restrictions. Pa-tients must have a biopsy within three months prior to registration and agree to have tissue specimens submitted. There must be no interven-ing treatment between biopsy and registration.

Patients must have adequate hematologic, he-patic, and renal function and a Zubrod perform-ance status of 0, 1, or 2.

Accrual Goals Initially 30 patients will be accrued. If nine or more patients survive without disease progression for at least six months, an additional 25 patients will be accrued.

Summary Statement This study entered temporary closure on June 1, 2002 for analysis of patient data from the first stage of the study. There have been 30 patients registered. Two patients are ineligible due to missing documentation, but these ineligibilities are potentially reversible.

Twenty-two patients are off treatment. There have been no major protocol deviations. Twenty-two patients have been assessed for toxicities. The following Grade 4 toxicities were reported: creatinine increase (1) and cerebrovascular ischemia (1). One patient expired before toxici-ties were assessed. Another patient went off treat-ment before response was assessed.


S0031/II

Registration by Institution


Total Reg

City of Hope Med Ctr 5 Henry Ford-UCOP/Henry Ford Hosp 1

Columbia-Presby UCOP 5 Kansas City CCOP 1 Ozarks Reg CCOP 5 Kansas, U of 1 Southeast CCC CCOP 3 Kentucky, U of-UCOP/Kentucky, U of 1 Grand Rapids CCOP 2 Northwest CCOP 1 Wichita CCOP 2 Oregon Hlth Sci-UCOP/Oregon Hlth Sci Univ 1 BAMC/WHMC-UCOP/BAMC/WHMC 1 Total (14 Institutions) 30 Central IL CCOP 1

Registration, Eligibility, and Evaluability Data as of July 29, 2002

ZD1839 ZD1839 NUMBER REGISTERED 30 TOXICITY ASSESSMENT 28

INELIGIBLE 2 Evaluable 22 Insufficient Documentation 2 Not Evaluable 1 Reversible 2 Too Early 5 ELIG./ PEND. ELIG. 28 Analyzable, Pend. Elig. 6 RESPONSE ASSESSMENT Determinable 16 Not Determinable 1 Too Early 11

Patient Characteristics Data as of July 29, 2002

ZD1839 (n=28)

ZD1839 (n=28)

AGE RACE Median 68 .0 White (Non-Hispanic) 26 93% Minimum 47 Hispanic 1 4% Maximum 82 Asian 1 4% SEX Males 22 79% Females 6 21%


S0031/II

Treatment Summary Data as of July 29, 2002

ZD1839 NUMBER ON PROTOCOL TREATMENT 6

NUMBER OFF PROTOCOL TREATMENT 22 REASON OFF TREATMENT Treatment completed as planned 0 Toxicity or side effects 3 Refusal unrelated to toxicity 0 Progression/relapse 12 Death 0 Other - not protocol specified 2 Reason under review 5 MAJOR PROTOCOL DEVIATIONS 0

Number of Patients with a Given Type and Degree of Toxicity Data as of July 29, 2002

ZD1839 ZD1839 (n=22) (n=22)

Grade

Grade

TOXICITY Unk 0 1 2 3 4 5 TOXICITY Unk 0 1 2 3 4 5 Abdominal pain/cramping 0 21 0 0 1 0 0 Hyperkalemia 0 21 0 0 1 0 0 Alkaline phosphatase increase 0 15 5 2 0 0 0 Hypertension 0 21 0 1 0 0 0 Anemia 0 15 2 5 0 0 0 Hypomagnesemia 0 20 2 0 0 0 0 Anorexia 0 20 1 1 0 0 0 Hyponatremia 0 21 0 0 1 0 0 Bilirubin increase 0 21 1 0 0 0 0 Ileus 0 21 0 0 1 0 0 Conjunctivitis 0 21 0 1 0 0 0 Mouth dryness 0 20 1 1 0 0 0 Cerebrovascular ischemia 0 21 0 0 0 1 0 Nail changes 0 21 0 1 0 0 0 Constipation/bowel obstruction 0 20 1 1 0 0 0 Nausea 0 17 4 1 0 0 0 Cough 0 21 1 0 0 0 0 Pruritus 1 21 0 0 0 0 0 Creatinine increase 0 19 0 2 0 1 0 Rash/desquamation 0 10 6 3 3 0 0 Dehydration 0 19 2 0 1 0 0 Renal failure 0 21 0 0 1 0 0 Diarrhea without colostomy 0 14 7 0 1 0 0 SGOT (AST) increase 0 16 5 1 0 0 0 Dry eye 0 21 1 0 0 0 0 SGPT (ALT) increase 0 21 0 0 1 0 0 Dry skin 0 20 1 1 0 0 0 Stomatitis/pharyngitis 0 21 1 0 0 0 0 Dyspepsia/heartburn 0 21 1 0 0 0 0 Thrombocytopenia 0 21 1 0 0 0 0 Dyspnea 0 21 0 1 0 0 0 Vomiting 0 21 0 1 0 0 0 Epistaxis 0 20 2 0 0 0 0 Weight loss 0 21 1 0 0 0 0 Eye-other 0 21 1 0 0 0 0 Fatigue/malaise/lethargy 0 13 4 2 3 0 0 MAXIMUM GRADE Fever without neutropenia 0 21 1 0 0 0 0 ANY TOXICITY GI Mucositis, NOS 0 21 0 1 0 0 0 Number 0 1 7 4 8 2 0 Hand-foot skin reaction 0 20 0 1 1 0 0 Hematuria 0 21 0 0 1 0 0 Hypercalcemia 0 21 0 1 0 0 0


S0032/II

S0032 Phase II

Phase II Evaluation of Early Oral Estramustine, Oral Etoposide and Intravenous Paclitaxel in Combination with Hormone Therapy in Patients

with High-Risk Metastatic Adenocarcinoma of the Prostate

Study Coordinators: D Smith, M Hussain




Objectives To estimate the progression-free survival in pa-tients treated with combined androgen blockade and four cycles of estramustine, etoposide and paclitaxel.

To estimate overall survival in patients treated with combined androgen blockade and four cy-cles of estramustine, etoposide and paclitaxel.

To evaluate the type, frequency and severity of toxicity in this patient population.

To acquire specimens from patients for this clini-cal trial for future studies to correlate with pro-gression-free survival and overall survival.

Patient Population Patients must have a histologically or cytologi-cally proven diagnosis of adenocarcinoma of the prostate. All patients must have clinical Stage D2 as evidenced by soft tissue and/or bony metasta-ses. Patients must also have either visceral dis-ease or bone metastases to both the axial and ap-pendicular skeleton. Patients with a history of brain metastases or who currently have treated or untreated brain metastases are not eligible.

Patients on androgen suppression therapy prior to registration must have received less than one month of therapy (excluding neoadjuvant therapy given as part of their primary treatment). Patients must not have received any prior cytotoxic che-motherapy. Prior radiation therapy, biologic ther-apy or surgery is allowed. A prestudy PSA must be obtained for all patients.

Patients must have adequate cardiovascular, he-matologic, hepatic, and renal function and a Zubrod performance status of 0, 1, or 2. Patients with active thrombophlebitis, hypercoagulability, or pulmonary embolus are not eligible. Patients with a history of transient ischemic attacks or cerebrovascular accident with resultant neu-rologic deficit within one year prior to registra-tion are not eligible.

Accrual Goals Eighty patients will be accrued to this study.

Summary Statement Two patients were registered to this study as of June 30, 2002, both by LSU-Shreveport UCOP.


S0111/II

S0111 Phase II

A Phase II Trial of Epothilone B Analogue BMS-247550 (NSC #710428) Administered Every 21 days in Patients with Hormone Refractory Prostate

Cancer

Study Coordinators: M Hussain, P Lara




Objectives To assess the PSA response to BMS-247550 in patients with hormone refractory prostate cancer.

To assess the overall survival and progression-free survival rate in patients with hormone refrac-tory prostate cancer treated with BMS-247550.

To assess the objective response rate (confirmed complete and partial response) among those pa-tients with measurable disease.


To investigate in a preliminary manner the asso-ciation of tumor response with pretreatment pres-ence of serum proteins and antibodies. Novel pro-teomics technology will be employed including MALDI analysis of serum proteins and protein microarrays. Novel epitopes associated with tu-mor destruction will be detected using protein microarrays. In addition, gene expression changes will be monitored using cDNA microarrays.

Patient Population All patients must have a histologic diagnosis of Stage D1 or D2 adenocarcinoma of the prostate that is unresponsive or refractory to hormone therapy. Patients with a history of brain metasta-ses or who currently have treated or untreated brain metastases are not eligible.

Patients must have received prior hormonal ther-apy. Patients treated with orchiectomy are eligi-ble. If the patient has been treated with non-steroidal antiandrogens (e.g., flutamide or bicalu-

tamide), they must have been stopped at least 28 days prior to enrollment for flutamide and at least 42 days prior to enrollment for bicalutamide or nilutamide and patients must have demonstrated progression. One prior biologic therapy and prior radiation therapy is allowed (to less than 30% of the bone marrow only). No prior strontium or samarium is allowed. No prior chemotherapy is allowed. Patients must have had a biopsy of the metastatic site and a serum sample taken prior to registration and agree to have specimens submit-ted.

Patients must have a Zubrod performance status of 0-2. Patients must have adequate hematologic, hepatic, and renal function. Patients must have a PSA ≥ 5 ng/ml within 14 days prior to registra-tion.

Accrual Goals Twenty-five patients will be accrued. If five or more responses are observed, an additional 20 pa-tients will be accrued.

Summary Statement After starting as a limited institution study, this study opened to all SWOG institutions on July 15, 2002. As of June 30, 2002, ten patients had been registered to this study. Two patients are in-eligible for the following reasons: prestudy lab tests done > 7 days prior to registration (1) and CT scans done > 28 days prior to registration (1).

There were no Grade 4 or Grade 5 toxicities re-ported in the three patients evaluated for toxicity assessment.


S0111/II



Davis, U of CA-UCOP/Davis, U of CA 5

Wayne State U-UCOP/Wayne State Univ 3 Kansas, U of 1 PSOC UCOP/Puget Sound 1 Total (4 Institutions) 10


BMS-247550 BMS-247550 NUMBER REGISTERED 10 TOXICITY ASSESSMENT 8

INELIGIBLE 2 Evaluable 3 ELIG./ PEND. ELIG. 8 Too Early 5 Analyzable, Pend. Elig. 6 RESPONSE ASSESSMENT Determinable 1 Too Early 7


BMS-247550

(n=8) BMS-247550

(n=8)

AGE RACE Median 73 .5 White (Non-Hispanic) 5 63% Minimum 56 Black (Non-Hispanic) 2 25% Maximum 80 Pacific Islander 1 13%


S0121/II

S0121 Phase II

Evaluation of Carboplatin, Paclitaxel and Gemcitabine Followed by Concurrent Cisplatin and Radiation Therapy in Patients with Locally

Advanced or Recurrent Urothelial Malignancy

Study Coordinators: U Vaishampayan, M Hussain



Objectives The primary objective of this study is to assess the overall survival of locally advanced or recur-rent inoperable urothelial carcinoma patients re-ceiving this treatment regimen.

Secondary objectives include the following:

To assess the progression-free survival in this group of patients.

To assess the feasibility of administering chemo-therapy prior to concurrent cisplatin and radiation therapy.

To assess qualitative and quantitative toxicities of this regimen.

To assess, in those with measurable disease, the unconfirmed response rate to the neoadjuvant chemotherapy, and to assess the response rate (confirmed and unconfirmed CR and PR) to the regimen as a whole.

To estimate the proportion of patients who qual-ify for the concurrent chemotherapy and radiation therapy.

To perform an exploratory study to assess the po-tential value of suppressor gene expression analy-sis (p53 and retinoblastoma gene) and Her 2 ex-pression as indicators of prognosis and/or re-sponse.

Patient Population Patients must have histologically (transitional, squamous or mixed) proven primary or recurrent urothelial cancer (primary: urinary bladder, renal

pelvis or urethra) which is measurable or evalu-able and confined to the pelvis (T2 - T4, N0-N3, M0) with one or more of the following criteria: nodal involvement at or below the level of the bi-furcation of the iliac vessels, inoperable disease due to medical or surgical reasons or patient re-fusal. Evidence of tumor invasion of the muscu-laris must be documented with detailed bladder mapping of extent of tumor by cystoscopy with biopsies.

Patients must have consulted with a radiation on-cologist within 28 days prior to registration. Ra-diation treatment must be given at a SWOG ap-proved facility. Prior adjuvant chemotherapy is permitted if completed more than six months prior to registration and if it did not contain car-boplatin, paclitaxel, or gemcitabine. No prior chemotherapy for the current diagnosis of ad-vanced bladder cancer is allowed.

Patients must have a Zubrod performance status of 0-2 and adequate renal, hepatic and bone mar-row function. Patients must not have pre-existing gastrointestinal disorders (see protocol for de-tails). Patients must not have an unresolved bacte-rial infection requiring treatment with antibiotics.

All patients must be offered participation on the correlative studies outlined in Section 15.0 of the protocol.

Accrual Goals Eighty eligible patients will be accrued to this study.


S0207/II

S0207 Phase II

Phase II Study of Arsenic Trioxide in Patients with Refractory Germ Cell Malignancies

Study Coordinators: T Beer, C Nichols

Statisticians: J Faulkner, C Tangen

Data Coordinator: K Bingham


Objectives To assess the response rate (confirmed complete and partial responses) in patients with refractory germ cell malignancies treated with arsenic triox-ide.

To assess the overall survival and progression-free survival in this group of patients.


Patient Population Patients must have a prior histologic confirmation of a testicular germ cell neoplasm. The disease must be refractory, defined as having progressed (per protocol) during or within four weeks of cis-platin-containing therapy, or recurred after at least two chemotherapy regimens. One of the two regimens must have included stem cell support unless the patient was not eligible for high-dose chemotherapy with stem cell support. Patients must have unidimensionally measurable disease or elevated Beta-HCG (> 20 mlU/ml) or AFP > 2 x IULN.

Patients must not have had treatment with cyto-toxic or experimental agents within 28 days prior to registration. Patients may have received prior radiation therapy.

Patients must not have a hypersensitivity to arse-nic, a history of torsades de pointes type ventricu-lar arrhythmia, or a prolonged QT interval > 450 msec on baseline ECG in the presence of normal serum potassium and magnesium values. Patients must not be receiving or planning to receive drugs known to prolong the QT interval. Patients must have Zubrod performance status ≤ 2 and adequate hemotalogic, hepatic, renal, and meta-bolic function. Patients must have LDH obtained within 28 days prior to registration.

Accrual Goals Initially, 20 patients will be accrued. If a response is observed in at least one patient, then an addi-tional 20 patients will be accrued.

Summary Statement As of June 30, 2002, one patient had been regis-tered to this study (U. of Kansas).


S0219/II

S0219 Phase II

A Sequential Approach to the Treatment of Muscle Invasive, Non-metastatic Urothelial Carcinoma of the Bladder: A Phase II Trial of Neoadjuvant

Gemcitabine, Paclitaxel and Carboplatin with Molecular Correlates

Study Coordinators: P Lara, R DeVere White



Schema

REGISTRATION

>pT0Neoadjuvantchemotherapy(Gemcitabine +Paclitaxel +Carboplatin,3 cycles)

TURBT within4-8 weeks ofchemotherapy

Immediatecystectomy

pT0*

Observation

Immediatecystectomy

*Action decided after balanceddiscussion with physician

Objectives The primary objective of this study is to deter-mine if a sequential approach to the treatment of muscle invasive urothelial carcinoma can result in pathologic complete responses to neoadjuvant chemotherapy.

Secondary objectives include:

To assess in a preliminary manner if molecular markers can predict response and survival in pa-tients with T2-T4, N0, M0 transitional cell carci-noma of the urothelial tract, or whether markers can predict tumor recurrence in patients who elect observation following an initial pathologic re-sponse.

To evaluate recurrence rates and cystectomy-free survival in patients who elect observation follow-ing an initial response to chemotherapy.

To evaluate the survival of patients treated post-TURBT with either chemotherapy alone, or neo-adjuvant chemotherapy followed by cystectomy.

To evaluate the feasibility, tolerability, and toxic-ity of this treatment paradigm.

Patient Population Patients must have histologically confirmed mus-cle invasive (T2-T4a), node negative (N0), transi-tional cell cancer of the urothelial tract (bladder, renal pelvis, ureter, urethra). Patients with adeno-carcinoma, small cell carcinoma, sarcomas or squamous cell carcinoma, or mixed adeno/squamous/transitional histology are not eligible. Measurable disease is not required. Pa-tients must have muscle invasive TCC (with no clinical evidence of metastatic disease) diagnosed by an initial TURBT, and must have undergone a repeat TURBT. The second TURBT must have been done within eight weeks of the first TURBT with the attempt to remove all tumor present. Pa-


S0219/II

tients with residual disease at the second TURBT will be eligible for the study. Patients must have pretreatment tumor tissue available from at least one of the prestudy TURBTs and agree to have tissue specimens submitted per protocol for analysis.

Patients must not have received any prior sys-temic chemotherapy or radiation therapy for this malignancy. Patients must not be planning to re-ceive any concurrent radiation therapy. Prior in-

travesical chemotherapy/immunotherapy is al-lowed.

Patients must have adequate hematologic, he-patic, and renal function and must have a Zubrod performance status of 0-2. Patients who are con-sidered at prohibitive medical risk for radical cys-tectomy in the opinion of the treating physician will not be eligible for this study.

Accrual Goals The accrual goal is 95 eligible patients.


30904/III

30904 Phase III Intergroup Coordinating Group: EORTC

A Prospective Randomized Phase III Study Comparing Radical Surgery to Elective Kidney Sparing Surgery for Low Stage Renal Cell Carcinoma: An

Intergroup Study

Intergroup Participants: EORTC, SWOG, ACOSOG, ECOG, NCIC

Study Coordinators: H van Poppel (EORTC), E Skinner, L Klotz (NCIC), T Keane (ECOG), L Gomella (ACOSOG)




Schema

RANDOMIZE

Elective Kidney Sparing Surgery

Radical Surgery

Objectives To study the possible curative effect of a partial resection in patients with a single, low stage, non-metastatic, well localized and well delineated re-nal cell carcinoma by studying time to recurrence and duration of survival.

To establish the side-effects of kidney sparing tumor resection in terms of operative morbidity and mortality.

To study the relationship between tumor size, his-tologic grade, histologic type and the result of lo-cal control by partial resection.

To determine which prognostic factors are impor-tant in selecting candidates for conservative sur-gery.

Patient Population Patients must have solitary T1-T2 renal tumors suspicious for renal andenocarcinoma, in the

presence of a normal contralateral kidney. The tumor must be single on a CT scan and not ex-ceed 5 cm in diameter. The tumor must be well located so that surgery can safely be done in healthy tissue. Patients must have no clinical presence of distant or lymphatic metastases.

Patients must be fit for surgery and have a WHO performance status of 0-2. Patients must not have von Hippel-Lindau disease.

Accrual Goals The accrual goal for this study is 1,300 patients.

Summary Statement According to EORTC, a total of 497 patients were registered to this study as of February 11, 2002. As of June 30, 2002, two patients had been registered through SWOG by the following insti-tutions: San Antonio, TX-UCOP(1), and So Calif, U of-UCOP(1).


30904/III

At the request of the Southwest Oncology Group, the EORTC reviewed their policy of excluding laproscopic surgery on this study and chose not to change it.

The complete February 2002 summary of this study from EORTC is available on the Southwest Oncology Group web site.


30987/III


Randomized Phase III Study Comparing Paclitaxel/Cisplatin/Gemcitabine and Cisplatin/Gemcitabine in Patients with Metastatic or Locally Advanced

Urothelial Cancer without Prior Systemic Therapy

Participants: EORTC, SWOG, NCIC, RTOG, CTSU

Study Coordinators: J Bellmunt (EORTC), D Smith, M Moore (NCIC), D Kaufman (RTOG)




Schema

RANDOMIZE

Cisplatin + Gemcitabine + Paclitaxel

Cisplatin + Gemcitabine

Objectives The primary objective of this study is to compare the duration of survival in the two treatment groups.

The secondary objectives are to compare the du-ration of progression-free survival, response rates (RECIST) and duration of response in the two treatment groups, and to compare and character-ize the nature of the toxicity experienced in each arm.

Patient Population Patients must have histologically proven stage IV locally advanced (T4b, N0-N1) or metastatic (N2, N3, or M1) transitional cell carcinoma of the urothelium (pure or mixed) including bladder, ureter, and renal pelvis. Patients must have meas-urable disease and/or non-measurable (evaluable) disease as defined in the RECIST criteria. Pa-

tients should not be suitable for surgery or radia-tion with curative intent. Patients with treated in-cidental Stage T1 prostate cancer with a Gleason score ≤ 6 and PSA < 0.5 ng/ml are eligible.

Patients must not have received any prior sys-temic chemotherapy or investigational agents for this cancer. Local intravesical chemotherapy or immunotherapy, or one course of prior radiation therapy are allowed with restrictions.

Patients must be 18 years of age or older and have a WHO performance status of 0 or 1. Pa-tients must have adequate liver, renal and cardiac function, adequate bone marrow reserve, and cor-rected calcium within the upper limit of normal. Patients with Grade 2 or greater peripheral neu-ropathy or Grade 3 or greater infection without neutropenia by CTC version 2.0, known central nervous system metastases, or serious concomi-


30987/III

tant systemic disorders incompatible with the study are excluded.

Stratification/Descriptive Factors Patients are stratified by (1) participating coop-erative group, (2) performance status: 0 vs 1, and (3) presence of metastatic disease: yes vs no.

Accrual Goals The accrual goal is 610 eligible patients. Two in-terim analyses will be performed: the first after toxicity data are available for the first 44 patients

on each treatment arm and the second after a total of 250 patients have been randomized.

Summary Statement This study was activated by EORTC on May 9, 2001. According to EORTC, there were 34 pa-tients registered to this study as of February 11, 2002. SWOG activated this study on June 15, 2002, with no registrations as of June 30, 2002.

The complete February 2002 summary of this study from EORTC is available on the Southwest Oncology Group web site.


30994/III


Randomized Phase III Trial Comparing Immediate Versus Deferred Chemotherapy After Radical Cystectomy in Patients with pT3-pT4 and/or

N+ M0 Transitional Cell Carcinoma (TCC) of the Bladder

Participants: EORTC, SWOG, ACOSOG, NCIC, CTSU

Study Coordinators: C Sternberg (EORTC), M Benson (SWOG), I Tannock (ACOSOG), M Moore (NCIC)



Schema

RANDOMIZE

Immediate Chemotherapy:Gem/Cis x 4 cycles

Deferred Chemotherapy:Gem/Cis x 6 cycles at time of clinical relapse

Objectives To compare the survival of patients with T3-T4 or N+ bladder cancer randomized after radical cystectomy between immediate adjuvant chemo-therapy or deferred chemotherapy at relapse.

To compare progression-free survival in these pa-tients.

Patient Population Patients must have histologically proven transi-tional cell carcinoma (TCC) of the urothelium, including bladder, urethra, ureter, and renal pel-vis, which is pT3 or pT4 and/or node positive (pN1-3). Radical cystectomy and lymphadenec-tomy are required with no evidence of any micro-scopic residual disease. Patients must have no evidence of metastatic disease (M0). Patients with mixed tumors comprising TCC and squamous or adenocarcinoma are not eligible.

No more than 90 days must have elapsed from cystectomy to the planned start of protocol treat-ment. Patients must not have had prior systemic chemotherapy or radiation to the bladder.

Patients must have a WHO performance status of 0 or 1, and they must have adequate hematologic, renal, hepatic, and cardiac function. Patients must also have clinically normal auditory function. Pa-tients considered unfit for cisplatin containing combination chemotherapy are not eligible.

Stratification/Descriptive Factors Patients are stratified by (1) participating coop-erative group, (2) pT category: pT1-2 vs pT3 vs pT4, and (3) node status: node positive vs node negative with ≥ 15 nodes sampled vs node nega-tive with < 15 nodes sampled.


30994/III

Accrual Goals The accrual goal is 1,344 randomized patients.

Summary Statement This study was activated by EORTC on October 9, 2001, with no patients registered as of Febru-ary 11, 2002. This study has not yet been acti-vated by SWOG as of this writing.


4B951/III

4B951 Phase III Intergroup Coordinating Group: USC

MVAC in Organ-Confined Bladder Cancer Based on p53 Status

Intergroup Participants: USC, SWOG

Study Coordinators: R Cote (USC), S Lerner




Schema

REGISTER

NoReconfirmationforRandomization

p53(-)* ObservationRadicalCystectomyforTransitionalCellCarcinomaof Bladder R

ANDOMIZE

Registrationapprovalfrom USCStudyCoordinator

p53(+)*

ReconfirmationforRandomization

MVAC

Observation

* p53 status communicated to institution by the USC Study Coordinator

Observation

Objectives To compare the recurrence free and overall sur-vival of those patients demonstrating alterations in the p53 gene who are treated with MVAC to patients with tumors demonstrating p53 altera-tions who are observed.

To compare the recurrence free and overall sur-vival prospectively of patients in tumors demon-strating alterations in p53 who are observed to pa-tients with no p53 alterations who are also ob-served.

To allow for the examination of expression of p53 and other genes, particularly RB, p21 and

p16 involved in cell cycle regulation that may be involved in the response to chemotherapy.

Patient Population Patients must have undergone a radical cystec-tomy and bilateral pelvic lymphadenectomy. Pa-tients must have pathologic TCC from the defini-tive cystectomy specimen of P1, P2a or P2b, N0, M0; patients with TCC Pa, P0 or PIS, N0 M0 and clinical stage T1, T2a, or T2b based on a TURBT specimen are eligible. Pure adenocarcinoma, squamous cell carcinoma, and small cell carci-noma neuroendocrine are ineligible. In cases where there is no evidence of invasive TCC in the


4B951/III

cystectomy specimen, patients will be eligible if they have invasive disease in the pre-cystectomy TURBT (T1 or T2). Metastatic disease must be ruled out per protocol specifications. Patients must be registered within nine weeks after the cystectomy, and patients must be judged by the investigator to be potentially curable and deemed suitable for chemotherapy. A representative par-affin block from the cystectomy or TURBT specimen must be available for submission. Pa-tients may have prostate adenocarcinoma stage pT2a or pT2b with a Gleason score ≤ 7 if it was found at the time of the cystectomy. Higher stages or Gleason's score ≥ 8 are not eligible.

Patients must not have received any systemic chemotherapy within five years of registration, and they must not have ever received prior sys-temic chemotherapy for bladder cancer. Patients may have had prior intravesical therapy, but prior pelvic irradiation is not allowed.

Patients must have adequate renal, hepatic, car-diac and hematologic function. Patients must have an ECOG performance status of 0 or 1, and must be approved by a USC study coordinator prior to registration to this study.

For randomization, patients must have been pre-viously registered and confirmed to have p53 al-terations in the tumor specimen by Dr. Cote's

laboratory at USC. Patients must re-affirm con-sent to the randomization aspect of the trial, and be randomized within 10 weeks after the cystec-tomy. Patients must have an ECOG performance status of 0 or 1, adequate renal, hepatic, cardiac and hematologic function and no clinical evi-dence of metastatic disease. Chemotherapy must begin within 12 weeks after cystectomy.

Stratification/Descriptive Factors At randomization patients will be stratified by (1) age: < 65 years vs ≥ 65 years; (2) stage: P1/T1 vs P2a/T2 or P2b/T2; (3) grade: 1-2 vs 3-4; and (4) p21 status: present vs absent.

Accrual Goals One hundred ninety patients who are positive for p53 will be randomized to adjuvant chemother-apy or observation.

Summary Statement According to USC, there were 292 patients regis-tered to this study as of June 30, 2002. Of those, 58 patients positive for p53 were randomized to treatment. As of June 30, 2002, 12 patients had been registered by SWOG, two of which were randomized to treatment.

The July 2002 summary report from USC is available on the Southwest Oncology Group web site.



So Calif, U of-UCOP/So Calif, U of 5

Baylor College-UCOP 4 Wayne State U-UCOP/Wayne State Univ 2 Michigan, U of-UCOP 1 Total (4 Institutions) 12


C90003/II

C90003 Phase II Intergroup Coordinating Group: CALGB

Adoptive Immunotherapy by Allogeneic Stem Cell Transplantation for Metastatic Renal Cell Carcinoma

Intergroup Participants: CALGB, SWOG, ECOG

Study Coordinators: B Rini (CALGB), K Margolin, D Avigan (ECOG)



Objectives To determine the overall objective response rate of adoptive immunotherapy delivered by alloge-neic stem cell transplantation following a non-myeloablative conditioning regimen.

To describe overall and disease-free survival in this group of patients.

To estimate the toxicity and treatment-related mortality of this treatment.

To determine the risk of acute and chronic graft versus host disease.

To assess engraftment of donor cells and to de-termine percent donor chimerism in myeloid and T cell lymphocyte subsets.

Patient Population Patients must have histologic documentation of metastatic or unresectable renal cell carcinoma (RCC). Patients with clear cell or papillary RCC, including clear cell or granular tumors with sar-comatoid features, are eligible. Patients with purely sarcomatoid RCC, chromophobic RCC, oncocytoma, or transitional cell carcinoma of the renal pelvis and collecting systems are not eligi-ble. If a renal mass and metastatic disease are ap-parent radiographically, and a nephrectomy will not be undertaken, then there must be histologic documentation of RCC, either from the primary renal mass or from a metastatic lesion. Patients

must have no evidence of current or prior metas-tases to the central nervous system.

Patients must have received prior interferon-alpha and/or interleukin-2 for metastatic RCC and have progressive disease or be intolerant of this ther-apy. Other prior systemic therapy is permitted, but no systemic therapies for RCC within 28 days prior to registration are allowed, including hor-monal therapies. Prior radiation therapy and sur-gery are allowed.

Patients must have an identified eligible (per pro-tocol) HLA Identical Sibling Donor. Patients must have a CTC (ECOG) performance status ≤ 1 and be ≤ 60 years of age. Patients must be HIV negative, have no uncontrolled diabetes mellitus or active serious infection, and no known hyper-sensitivity to E. coli-derived products. Patients must have adequate cardiac, hematologic, he-patic, and renal function.

Accrual Goals The accrual goal is 36 eligible patients.

Summary Statement This study was opened by CALGB on October 15, 2001 with no patients registered to date. The June 2002 summary report from CALGB is available on the Southwest Oncology Group web site.


C9687/II

C9687 Phase II Intergroup Coordinating Group: CALGB

The Role of Salvage Prostatectomy for Radiation Failure in Prostate Carcinoma

Intergroup Participants: CALGB, SWOG

Study Coordinators: G Steinberg (CALGB), J Basler




Schema

REGISTER

+ node(s)*

- node(s)

Modified bilaterallymph nodedissection

Off Protocol Treatment

Salvage Prostatectomy

* If nodes are microscopically positive, prostatectomy may proceedat discretion of the investigator

Objectives To estimate the characteristics of the surgical morbidity and mortality, and the quality of life for patients treated with salvage prostatectomy for recurrent or persistent disease after treatment with radiation therapy for localized prostate can-cer.

To develop expertise in the use of salvage prostatectomy prior to a possible phase III trial of salvage prostatectomy in this population versus a control arm such as hormonal therapy (immediate or delayed) or cryotherapy.

To provide preliminary data on the quality of life of patients undergoing salvage radical prostatec-tomy and to use the data to design a phase III study; phase II data will assist in determination of

the timing of quality of life assessments and util-ity of measures selected.

To estimate the characteristics of the PSA failure-free survival, disease-free survival, and the over-all survival for patients treated with salvage prostatectomy for recurrence or persistent disease after treatment with radiation therapy for local-ized prostate cancer.

To determine the histologic and morphometric characterization of the carcinoma.

Patient Population Patients must have biopsy-proven persistence or recurrence of prostate cancer. There can be no evidence of metastatic disease at the time of the biopsy.

Patients must have been treated with ≥ 60 cGy external beam radiation therapy or brachytherapy


C9687/II

for clinical stages T1-2,NX,M0 prostate cancer with PSA ≤ 30 ng/ml prior to radiation therapy. Radiation therapy must have been completed at least 18 months prior to registration, and if adju-vant hormonal therapy was received it must have been completed at least three months prior to reg-istration.

Patients must have a PSA ≤ 20 ng/ml and a per-formance status of 0 or 1 within 30 days prior to registration. Patients must not have any of the fol-lowing: an active acute infection requiring antibi-otics, uncontrolled or severe cardiovascular dis-ease including a myocardial infarction or conges-tive heart failure in the last six months, a serious intercurrent illness that would compromise pa-

tient care, or a psychiatric condition which would prevent compliance with treatment or adequate informed consent.

Accrual Goals The accrual goal for this study is 40 patients who receive a salvage prostatectomy.

Summary Statement According to CALGB, a total of 17 patients have been registered to this study as of June 30, 2002. One of those patients was registered by SWOG.

The complete June 2002 summary of this study from CALGB is available on the Southwest On-cology Group web site.


E1899/III:

E1899 Phase III: SWOG Endorsed CTSU Study Coordinating Group: ECOG

A Phase III Randomized Trial for Evaluating Second Line Hormonal Therapy (Ketoconazole/Hydrocortisone) versus Paclitaxel/Estramustine

Combination Chemotherapy on Progression-Free Survival in Asymptomatic Patients with a Rising PSA after Hormonal Therapy for Prostate Cancer

Participants: ECOG, CTSU

Study Coordinators: M Carducci (ECOG), G Swanson (SWOG)

Schema

RANDOMIZE

Ketoconazole + Hydrocortisone

Paclitaxel + Estramustine

Objectives To evaluate time to objective progression in men with a rising PSA after androgen suppression for prostate cancer with either second line hormonal therapy (ketoconazole/hydrocortisone) or a che-motherapy regimen (paclitaxel/EMP) and its rela-tionship to PSA.

To evaluate time to PSA progression for each arm and to correlate PSA progression with time to ob-jective progression.

To describe quality of life over time wth each arm.

To describe the natural history of progression for each treatment arm.

To follow each arm for overall survival.

Patient Population Patients must have documented adenocarcinoma of the prostate that has been treated with andro-gen suppression, and present with a rising PSA. Patients must have had Gleason sum 7 or higher and/or seminal vesical involvement at initial di-agnosis. Patients must not have had progressive or measurable local or any metastatic disease.

There must be no prior systemic chemotherapy within five years prior to registration. There must be no previous palliative radiation, but prior ra-diation to the primary site of disease is allowed if stopped at least 28 days prior to registration. Prior therapy with hydrocortisone is allowed (must have discontinued > 4 weeks prior to randomiza-tion), but prior therapy with ketoconazole is not allowed. There must not be plans for concomitant use of bisphosphonates or digitalis while on study treatment.

Patients must have adequate hepatic and renal function and an ECOG performance status of 0 or 1. Patients must have no history of severe cardio-vascular disease (AHA Class III or IV), uncon-trolled CHF, or life-threatening cardiac dys-rhythmias. Patients with a history of prior malig-nancy are eligible provided they were treated with curative intent and have been free of disease for the time period considered appropriate for the specific cancer.

Accrual Goals The accrual goal is 280 eligible patients per arm. Interim analyses are planned to take place at ap-


E1899/III:

proximately 43% and 79% of the total informa-tion, which is expected to occur at 36 months and 54 months.


E8897/BIOLOGIC

E8897 Biologic Intergroup Coordinating Group: ECOG

Correlation of Histopathology, Immunohistochemistry and Quantitative Radiology with Outcome in Early Stage Nonseminomatous Germ Cell

Tumor

Intergroup Participants: ECOG, SWOG

Study Coordinators: R Foster (ECOG), C Nichols



Schema

REGISTRATION Surveillance*

RPLND*

* The choice of treatment will bedetermined by treating physician afterdiscussion with the patient

Objectives To use histopathological and immunohistochemi-cal analysis of the primary testis tumor along with quantitative radiographic assessment to attempt to identify a subset of patients with clinical stage A nonseminoma who have a very low risk of recur-rence.

To compare these findings with other predictive models of risk of recurrence after orchiectomy in this group of patients.

Patient Population Patients must have clinical Stage A nonsemino-matous germ cell tumor of the testis. Patients should have no pure seminoma (unless associated with elevated AFP at diagnosis). Patients should have no evidence of metastatic disease on physi-cal exam, chest x-ray, or abdominal/pelvic CT. AFP and HCG must be normal or values falling after orchiectomy at a rate consistent with known half-lives.


E8897/BIOLOGIC

Patients must have had a radical inguinal orchiec-tomy or simultaneous orchiectomy and retroperi-toneal lymph node dissection (RPLND) within 12 weeks prior to registration. Patients managed with primary chemotherapy are not allowed.

Patients having prior history of malignancy, in-cluding prior testis primary, are not allowed. Pa-tients must be at least 15 years old.

Accrual Goals The accrual goal for this study is 315 patients.

Summary Statement ECOG activated this study on May 26, 1999. As of June 30, 2002 there were 57 patients regis-tered.

The complete June 2002 summary of this study from ECOG is available on the Southwest Oncol-ogy Group web site.


JPR3/III

JPR3 Phase III Intergroup Coordinating Group: NCIC

Phase III Randomized Trial Comparing Total Androgen Blockade Versus Total Androgen Blockade Plus Pelvic Irradiation in Clinical Stage T3-4, N0,

M0 Adenocarcinoma of the Prostate

Intergroup Participants: NCIC, SWOG, CALGB, ECOG

Study Coordinators: P Warde (NCIC), G Swanson, S Vijayakumar (CALGB), R Whittington (ECOG)




Schema

RANDOMIZE

Flutamide + Hormonal therapy

Flutamide + Hormonal therapy + Radiation therapy

Objectives To evaluate any possible benefit from the addi-tion of external radiation therapy to the treatment of patients with locally advanced (T3 or T4, N0 or NX, M0 or T2, PSA>40 or T2, PSA>20 and Gleason≥8) cancer of the prostate who have not had a radical prostatectomy and are receiving hormonal therapy in terms of the following end-points: overall survival, time to disease progres-sion, and symptomatic local control as measured by the rates of surgical interventions necessary for symptomatic local disease (i.e. the combined incidences of trans-urethral resections, stent insertions, nephrostomies and colostomies).

Quality of life will be measured by QLQ-C30+3 and trial specific checklist (PR17) or FACT-P to (a) describe quality of life of patients with pros-tate cancer treated with hormones from the time of diagnosis to death; (b) determine whether addi-tion of prostate irradiation affects patients' quality of life; and (c) assess responsiveness to change of

two quality of life instruments (QLQ-C30+3 and FACT-P).

Patient Population Patients must have a histological diagnosis of lo-cally advanced adenocarcinoma of the prostate (T3-4, N0 or NX, M0 or T2, PSA > 40 or T2, PSA > 20 and Gleason ≥ 8) within six months prior to randomization. All pelvic lymph nodes must be clinically negative. The patient must have a bone scan showing no evidence of bony metastases within 16 weeks prior to randomiza-tion.

Patients must not have had any prior treatment for carcinoma of the prostate apart from trans-urethral resection or hormonal therapy. The pa-tient may have received prior hormone therapy during the 12 weeks prior to randomization with restrictions. Patients may have received treatment with a 5 alpha-reductase inhibitor (e.g. Finas-teride) for BPH but must have discontinued use at


JPR3/III

least 4 to 6 weeks before randomization PSA level.

Patients must have adequate hematologic, he-patic, and renal function and have an ECOG per-formance status of 0, 1 or 2.

Stratification/Descriptive Factors Patients will be stratified by (1) cooperative group; (2) initial PSA level: < 20 vs 20-50 vs > 50; (3) choice of hormonal therapy: bilateral or-chiectomy (+/- antiandrogen) vs LHRH agonist + antiandrogen; (4) method of lymph node staging: clinical vs radiological vs surgical dissection; (5) Gleason score: < 8 vs 8-10; and (6) prior hor-

mone therapy (excluding orchiectomy): yes vs no.

Accrual Goals The accrual goal is 650 eligible patients. Two in-terim analyses will be performed: the first after approximately 110 events (deaths) and the second after approximately 220 events.

Summary Statement According to the NCIC, a total of 638 patients have been registered to this study as of June 30, 2002. Thirty-seven of these patients were regis-tered by SWOG.



LSU-Shreveport UCOP/LSU-Shreveport 13

Tulane U - UCOP/Tulane University 9 San Antonio, TX-UCOP/San Antonio, U of TX 7 BAMC/WHMC-UCOP/BAMC/WHMC 5 Hawaii CCOP, Univ of 3 Total (5 Institutions) 37


JPR7/III

JPR7 Phase III Intergroup Coordinating Group: NCIC

A Phase III Randomized Trial Comparing Intermittent Versus Continuous Androgen Suppression for Patients with Prostate-Specific-Antigen

Progression in the Clinical Absence of Distant Metastases Following Radiotherapy for Prostate Cancer

Intergroup Participants: NCIC, SWOG

Study Coordinators: J Crook (NCIC), C Higano




Schema

RANDOMIZE

Continuous Androgen Deprivation

Intermittent Androgen Suppression

Objectives To compare the survival of patients randomized to intermittent androgen suppression (IAS) to that of patients randomized to continuous androgen deprivation (CAD) for patients with PSA evi-dence of progression in the clinical absence of distant metastases following previous radical ra-diotherapy treatment of prostate cancer.

To compare the time to the development of hor-mone-resistance in patients randomized to inter-mittent androgen suppression (IAS) to that of pa-tients randomized to continuous androgen depri-vation (CAD) in this patient group.

To compare the effect of these treatments on measures of quality of life in this patient group, by using the EORTC QLQ-C30 and trial specific questionnaire.

To compare the serum cholesterol and HDL/LDL levels at three years with those at baseline, and to compare them annually between the patients ran-domized to intermittent androgen suppression (IAS) to that of patients randomized to continu-ous androgen deprivation (CAD) in this patient population.

Additional objectives on the Intermittent (IAS) Arm are to evaluate the duration of treatment and non-treatment intervals, the time to testosterone recovery (return to pre-therapy levels), and the time to recovery of potency.

Patient Population Patients must have histologically or cytologically confirmed adenocarcinoma of the prostate prior to initiation of radiotherapy. Patients must have no definitive evidence of metastatic disease. Pa-tients must have elevated serum testosterone (>


JPR7/III

145 ng/dl) and must have serum PSA > 6 ng/ml and higher than the lowest level recorded previ-ously since the end of radiotherapy (i.e., higher than the post-radiotherapy nadir).

Patients must have had previous pelvic radiother-apy for prostate cancer, either post radical prostatectomy or as primary management. Pa-tients treated with brachytherapy with curative in-tent as the primary form of radiotherapy are eligi-ble. Patients must not have had any radiotherapy within 12 months prior to randomization. Patients must not have had prior hormonal therapy with the exception of neo-adjuvant cytoreduction for a maximum duration of 8 months prior to radio-therapy or prostatectomy.

Patients must have adequate hepatic and renal function and a ECOG performance status of 0 or 1. Patients must be able to read and understand English or French in order to participate in the Quality of Life portion of the study.

Stratification/Descriptive Factors Patients will be stratified by (1) prior radical prostatectomy: yes vs no; (2) time since comple-tion of the radical radiotherapy: 1 to 3 years vs ≥ 3 years; (3) baseline PSA value: 6 ng/ml to 15 ng/ml vs > 15 ng/ml; and (4) neo-adjuvant cy-toreduction (for a maximum of 8 months) prior to radical radiotherapy treatment or prostatectomy: yes vs no.

Accrual Goals Patient accrual will be 1,340 for this study. A formal interim analysis will be performed at ap-proximately 400 events (deaths).

Summary Statement According to the NCIC, a total of 596 patients have been registered to this study as of June 30, 2002. Seventy-seven of these patients were regis-tered by SWOG.



Total Reg

E Virginia UCOP 17 Colorado, U of-UCOP/Colorado, U of 1

Columbia-Presby UCOP 11 Columbus CCOP 1 Ann Arbor Reg CCOP 10 Cottage Health Sys/Los Angeles, U of CA 1 Kansas, U of 6 Greater Phoenix CCOP 1 St Joseph Hospital/Puget Sound 5 Hawaii CCOP, Univ of 1 Davis, U of CA-UCOP/Davis, U of CA 3 Huntington Mem Hosp/So Calif, U of 1 Boston Univ Med Ctr 2 Loyola/Hines VA-UCOP/Loyola University 1 Greenville CCOP 2 LSU-Shreveport UCOP/LSU-Shreveport 1 Southeast CCC CCOP 2 Providence Gen MC/Puget Sound 1 Tulane U - UCOP/Tulane University 2 PSOC UCOP/Puget Sound 1 Virginia Mason UCOP/Virginia Mason CCOP 2 U of Illinois MBCCOP 1 Wayne State U-UCOP/Wayne State Univ 2 Wichita CCOP 1 Bay Medical Center/Michigan, U of 1 Total (25 Institutions) 77


MDA-3410/III:

MDA-3410 Phase III: SWOG Endorsed CTSU Study Coordinating Group: MDACC

A Prospective Randomized Phase III Trial Comparing Consolidation Therapy with or without Strontium-89 Following Induction Chemotherapy

in Androgen-Independent Prostate Cancer

Participants: MDACC, CTSU

Study Coordinators: S Tu (MDACC), J Pinski (SWOG)

Schema

RANDOMIZATION

Sr-89 + Doxorubicin

No PSAresponse at16 weeks

Off protocol treatment

PSAresponse at16 weeks

Doxorubicin

REGISTRATION

InductionChemo*

* See protocol for options

Objectives To compare the effectiveness, as measured by overall survival, of consolidation therapy with or without strontium-89 following induction chemo-therapy in selected patients with androgen-independent prostate cancer.

To collect serial serum, urine, and bone marrow for the study of bone-epithelial markers.

Patient Population Patients must have androgen-independent adeno-carcinoma of the prostate, and must exhibit with-drawal of anti-androgens such as flutamide, bi-calutamide, or nilutamide. No evidence of re-sponse after anti-androgen withdrawal within four weeks for flutamide, six weeks for others is allowed. Patients must have a rising PSA on at least two occasions ≥ one week apart (minimum value of 5 ng/ml), accompanied either by bone pain or, if the patient is asymptomatic, by a wors-

ening bone scan with new lesions over a period of < six months. Patients must have a castrate testos-terone level ≤ 50 ng/ml, and must have osteoblas-tic metastases as evidenced by bone scan or CT scan.

No prior Sr-89 nor Sm-153 treatment is allowed, and no more than one prior cytotoxic treatment is allowed. Patients must not have had any chemo-therapy, immunotherapy, or radiotherapy within four weeks (six weeks for nitrosoureas or mito-mycin C) prior to registration and must have re-covered from any adverse events due to agents administered more than four weeks prior to regis-tration. Prior ketoconazole, doxorubicin, or vin-blastine use by patients on the KAVE arm, or prior docetaxel use by patients on the estra-mustine plus docetaxel arm is not allowed. Pa-tients must plan to continue treatment to maintain castrate levels of testosterone.


MDA-3410/III:

Patients must have adequate hematologic and he-patic function, and have an ECOG performance status ≤ 3. Patients must not have a history of al-lergic reactions to compounds of similar chemical or biologic composition to ones used in this trial. Patients with previous vagotomy or other condi-tions (such as pernicious anemia) associated with achlorhydria are not eligible, nor are patients with symptomatic lymphadenopathy (scrotal or pedal edema) or significant local invasive disease (he-maturia). Patients with recent history of transient ischemic attacks or myocardial infarctions within 12 months, or active angina or claudication suffi-cient to limit activity are not eligible.

Stratification/Descriptive Factors For randomization, patients will be stratified by the following factors: (1) induction chemother-apy: alternating sequential (KAVE) vs estra-mustine/docetaxel, (2) number of bony metasta-ses: ≤ 20 vs > 20, and (3) performance status: ECOG 0-1 vs 2-3.

Accrual Goals The accrual goal is 408 randomized patients. There will be three interim analyses, after totals of approximately 70, 140, and 210 deaths have been observed.

Summary Statement MD Anderson activated this study on April 16, 2002, with one registration as of June 30, 2002.

genitourinary committee 2002...bep + hd chemo + aubmt/stem cells 1 4 2 30 1 6 5 58 s9450...

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