R

System. Lymphadenectomy

pelvic

para-aortic

no Lymphadenectomy

epithelial invasive ovarian cancer

FIGO IIB - IV

ECOG 0/1 and no CI against LNE

no visible extra- and intra-abdominal

tumor residuals

no bulky lymph nodes

Endpoints: OS, PFS, QoL Strata: centre, PS ,age

Lymphadenectomy In Ovarian Neoplasms

AGO – OVAR OP.3 (LION)

80/ 640

Supported by Deutsche Forschungsgemeinschaft

Carbo Paclitaxel +/- BIBF 1120 (Vargatef)

Patients 0 / 1300 (2:1 random)

Leading AGO-OVAR

Participating AGO Austria, BGOG, GINECO,

MANGO, MITO, NSGO, US Oncology

AGO-OVAR-12

Multicenter, randomised, double-blind, Phase III trial to investigate the efficacy and safety of Vargatef (BIBF 1120) in combination with standard

treatment of carboplatin and paclitaxel compared to placebo plus carboplatin and paclitaxel patients with advanced ovarian cancer

AGO-OVAR12

R

CT

CT

CT

CT

CT

CT

CT

CT

CT

CT

CT

CT

= Vargatef 2 x 200 mg po qd

= Placebo

120 weeks

C = Carboplatin AUC 5-6 d1

T = Paclitaxel 175 mg/m2 (3h) d1

q21d / 6 courses

Vargatef / Placebo :- no intake on days of chemotherapy

- dose: 200 mg po bid (combi + mono)- dose adaptation in case of undue toxicity

- max. duration of 120 weeks in non-progressing pts

SURGERY

n=1300

Pazopanib consolidation 1 yrFirst Line Chemotherapy

Control

Patients 80 / 900

Leading AGO-OVAR

Participating AGO Austria, ANZGOG, BGOG, GEICO, GINECO, ICORG, JGOG, KGOG, MANGO, MITO, NSGO, US-Sites: California Consortium, NY GOG, SWOG

AGO-OVAR 16

AGO-OVAR16A Phase III Study to Evaluate the Efficacy and Safety of Pazopanib Monotherapy Versus Placebo in Women Who Have not Progressed after First Line Chemotherapy for Epithelial Ovarian, Fallopian Tube,

or Primary Peritoneal Cancer

Survival Follow-up(post-PD)

First-line Chemotherapy

(allow ip, neoadj) Placebo

(12 months)

Pazopanib (12 months)

If not PD

Treatment PeriodR

ANDOMIZE

Observation (to PD)

ScreeningBaseline

Post-Treatment Period

Follow-up Period

Carbo Topo vs Chemo (CT or CG) in recurrent Platinum-sensitive ovarian cancer

Patients 508 / 550

Leading NOGGO/AGO-OVAR

Participating AGO-AUSTRIA, GEICO

HECTOR

CT vs CDDP + Irinotecan

Patients 416 / 652

Leading JGOG

Participating GINECO, GOG, KGOG, MITO, SGCTG

JGOG-3017 Clear Cell Carcinoma

JGOG3017/GCIGOvarian Trial Protocols

Randomized Phase III Trial of Paclitaxel plus Carboplatin (TC) Therapy versus Irinotecan plus

Cisplatin (CPT-P) Therapy as a First Line Chemotherapy for Clear Cell Carcinoma of the Ovary

Study Chair Toru Sugiyama, MD (Iwate Medical University)Study Co-Chair Seiji Isonishi, MD (Jikei University School of Medicine)

Fumitoshi Terauchi, MD (Toho University)

RA

ND

OM

IZA

TIO

NTC

Paclitaxel 175 mg/m2 (d1) Carboplatin AUC 6 (d1)

Every 3 wk x 6

CPT-11/CDDP CPT-11 60 mg/m2 (d1, 8, 15)

Cisplatin 60 mg/m2 (d1)Every 4 wk x 6

International Cooperative Phase III Study for Clear Cell Carcinoma

-Clear Cell Ca

-Stage I~IV

225 patients in each arm, 450 total for 3 years

326 patients in each arm, 652 total for 4.25 years

JGOG3017/GCIG TRIAL

Weekly CT vs 3-weekly CT (QoL)

Patients 72 / 500

Leading MITO

Participating MaNGO, AGO-OVAR

MITO-7

Trial design

• Aim of the trial is to compare the quality of life of weekly somministration of carboplatin plus carboplatin (experimental arm) versus every 3 weeks administration of the same drugs (standard arm) in 1°-line advanced ovarian, tubal and peritoneal cancer

RANDOM

Carboplatin AUC 2Paclitaxel 60 mg/mq

day 1,8 15 - every 21days

Carboplatin AUC 6Paclitaxel 175 mg/mq

day 1 - every 21days

PLD vs CT cross-overin 6-12 m platinum-free interval

Patients 18 / 253

Leading MITO

Participating MaNGO, AGO-OVAR, Belgium

MITO-8

RANDOM

LIPOSOMALDOXORUBICIN

40 mg/mqday1 every 28 days

CARBOPLATIN AUC 5 +PACLITAXEL 175 mg/mq

day1 every 21 days

Cross-over atProgression

CARBOPLATIN AUC 5 +PACLITAXEL 175 mg/mq

day1 every21gg

LIPOSOMALDOXORUBICIN 40 mg/mq

day1 every 28 days

Trial design• The objective of this trial is the efficacy determined

through analysis of overall survival (OS) of the different sequence (CP→PLD vs PLD→CP) in recurrent ovarian cancer patients with platinum-free interval 6-12 months

ICON6: A randomised trial of concurrent (with platinum based chemotherapy) and maintenance

cediranib (AZD2171, Recentin) in women with platinum-sensitive relapsed ovarian cancer.

Gynaecologic Cancer Intergroup TrialStage 1 MRC/NCRI, NCIC

Stage 2 ANZ-GOG, IMN, EORTC, GINECO, GEICO, MANGO, NSGO, ICMB and others

ICON 6 Start up slidesOct 2009

ICON 6 Design schema

Arm AReference arm

6 cycles of chemotherapy

plusPlacebo

No Progressive disease

Maintenancecediranib after chemotherapy

Maximum 18 months from

randomisation

Arm BChemotherapy

Pluscediranib

during Chemotherapy

Arm CChemotherapy

pluscediranib

during Chemotherapy

No Progressive diseasePlacebo

Maximum 18 months from

randomisation

No Progressive diseasePlacebo

Maximum 18 months

from randomisation

2:3:3 RANDOMISATION

ICON6 Cediranib Dose Reduction

• Cediranib dose initially selected at 30mg/d in ICON6. Reduced to 20 mg

• Stage I re-started• Stage I now completed 103 patients

entered (11 UK; 6 CDN)• Stage II being prepared with expansion

of chemotherapy options to be discussed by ITMG Sunday 11th Oct- Belgrade

ICON 6 Start up slidesOct 2009

Planned TrialsPlanned Trials

Cytoreductive surgery vs NO surgery in platinum-sensitive recurrent EOC

Patients 0 / 385

Leading AGO-OVAR

Participating ?

AGO-OVAR-OP.4 DESKTOP III

AGO-OVAR-OP.2 DESKTOP II

Study collective: AGO score + 1st relapse129 pts (87%)

08/06 – 03/08: Screening of 516 pts with platinum-sensitive relapse in 46 centres

Score positive+

First relapse

Frequency of complete resection by applying the AGO Score

76%Completeresection

AGO-OVAR DESKTOP III (Protocol AGO - OVAR OP.4)

A randomized trial evaluating cytoreductive surgery in patients with platinum-sensitive recurrent ovarian cancer

Complete resection

seems feasible and a

positive AGO-score

Strata:

Platinum-free-interval

6-12 vs > 12 months

- 1st line platinum

based chx: yes vs no

RANDOM

Cytoreductivesurgery platinu

m-based

chemo-therapy

*recommende

d

no surgery

The next steps:

Protocol finalized (-> review participating groups)

Ethical approval for Germany:12/09 -> FPI 01/2010

Identifikation of interested GCIG-groups/single centres

-> representatives contact:

p.harter@gmx.de

office-wiesbaden@ago-ovar.de

Again limited funding - participating groups have to pay local costs

(DESKTOP II model – Presentation/Publication/Co-authorship)

AGO-OVAR DESKTOP III (Protocol AGO - OVAR OP.4)

Collaborative Nursing Study MITO12Pathway to diagnosis of ovarian cancer in Italian

women: an exploratory study

Primary Objectives• Describe the frequency and duration of symptoms in

the 12 months preceding the diagnosis of ovarian cancer (Goff symptoms survey)

• Describe time intervals of sentinel events– Onset of persistent symptoms– First physician visit– Diagnosis of ovarian cancer

• Describe the pathway to diagnosis according to Andersen’s model of “total patient delay”

Weekly Paclitaxel vs weekly Paclitaxel and Pazopanib in patients with

resistant/refractoryovarian cancer:

Phase II randomized multicenter trial

MITO - 11

Trial design

• Aim of the trial is to compare the PFS of weekly paclitaxel vs weekly paclitaxel and pazopanib

RANDOM

Pazopanib 800 mg/dayPaclitaxel 80 mg/mq

day 1,8 15 - every 28days

Paclitaxel 80 mg/mq

day 1, 8, 15 - every 28 days

IP vs IV carboplatin + weekly Paclitaxel

Patients

Leading JGOG

Participating

JGOG IP Trial

iPocc Trial DesignEpithelial Ovarian, Peritoneal,

Fallopian Tube CancerStages II-IV

Optimal, SuboptimalExcluding Clear Cell Carcinoma

Paclitaxel 80 mg/m2 IV WeeklyCarboplatin AUC 6 IV

Q21, 6-8 Cycles

Paclitaxel 80 mg/m2 IV WeeklyCarboplatin AUC 6 IP

Q21, 6-8 Cycles

Randomization

Primary Endpoint: PFSSecondary Endpoint: OS, Toxicity, QOL, Cost

oxaliplatin + capecitabine ± bevacizumab vs carboplatin + paclitaxel ± bevacizumab Patients 0/332

Leading NCRI/SGCTG GOG

Participating AGO OVAR, GINECO, MaNGO, NSGO, KGOG

MucinousEOC

Cancer Research UK & UCL Cancer Trials Centre

Targets: Planned start date – November 2009; Planned end date – May 2014 

European Sites: Interest from sites in

UK, Denmark, Finland, Sweden, Norway, France, Italy & Germany.

Approximately 40 UK sites interested. Trial is in set-up, no centres are open.

Chief Investigator: Prof. Martin Gore

Sponsor: University College London

http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=4667

Contact Email: mEOC@ctc.ucl.ac.uk

TC dose dense / 3weekly ± BEVACIZUMAB

Patients 0 / 2000

Leading MRC/NCRI

Participating ?

ICON-8

Randomisation

ARM1: C q 3/52 P q 3/52(current std)

ARM2: C q 3/52 P q 1/52

ARM3: C q 1/52 P q 1/52

Current Proposal

(A) Immediate Primary Surgery (IPS)

(B) Delayed Primary Surgery (DPS)

Surgery (IPS)

Surgery (DPS)

Chemotherapy(ARM 1-3 x 6)

Chemotherapy(Arm 1-3 x 3)

Chemotherapy (Arm 1-3 x 3)

One trial with pre-specified

stratification for IPD v DPS

Plan to use lower dose of paclitaxel than JOG for arm 2: Carboplatin AUC6 d1Paclitaxel 60mg/m2 d 1,8,15 q3w

JOG study 60% received 6 cycles, 48% required at least one dose reduction and 76% had at least one delay, doses used carboplatin AUC6 and paclitaxel 80 mg/m2

IP/IV Platinum/T vs IV CT optimally debulked following NACT

Patients 0 / 780

Leading NCIC CTG

Participating GEICO, NCRI, SWOG

NCIC CTG OV.21

Basic Design

Patients with EOC

3-4 cycles neoadjuvant chemo

Initial surgery: < 1 cm residual

3 cycles IV Carbo/Taxol

3 cycles IP/IV platinum and taxol

Endpoints: PFS and OS

RR

Day 8th Day 8th

Optimal Optimal SurgerySurgery

ShorteShorter r

coursecourse

Phase IIPatients will be randomized to one of the following three arms:

Arm Agent(s) Dose Route DurationSchedule

Days Repeat

1

Paclitaxel135 mg/m2

IV

3 hours Day 1

Every 21 days

60 mg/m2 1 hour Day 8

Carboplatin

AUC 5if measured GFR

(use AUC 6 if calculated GFR)

30 minutes*

Day 1

2

Paclitaxel

135 mg/m2 IV 3 hours Day 1

60 mg/m2 IPBy gravity as rapidly

as possibleDay 8

Cisplatin 75 mg/m2 IPBy gravity as rapidly

as possibleDay 1

3

Paclitaxel

135 mg/m2 IV 3 hours Day 1

60 mg/m2 IPBy gravity as rapidly

as possibleDay 8

Carboplatin

AUC 5if measured GFR

(use AUC 6 if calculated GFR)

IPBy gravity as rapidly

as possible

Day 1

* or according to local practice

Phase IIIPatients will be randomized to one of the following two arms:

Arm Agent(s) Dose Route Duration

Schedule

Days Repeat

1

Paclitaxel135 mg/m2

IV

3 hours Day 1

Every21 days

60 mg/m2 1 hour Day 8

Carboplatin

AUC 5if measured GFR

(use AUC 6 if calculated GFR)30 minutes* Day 1

2 The selected IP arm from Phase II (regimen as in above table)

Every21 days

* or according to local practice

A randomised phase III trial of weekly carboplatin and paclitaxel versus pegylated liposomal doxorubicin in recurrent, platinum resistant, epithelial ovarian cancer

Patients 0 / 250

Leading SGCTG

Participating ?

DDPC-PREOC

Trial Design

Carboplatin (AUC 3) and paclitaxel (80 mg/m2) for 3 weeks out of 4 for 6 cycles

Pegylated Liposomal Doxorubicin (40 mg/m2) every 4 weeks for 6 cycles

RANDOMISE

250 patients with platinum resistant disease

Primary Endpoint: PFS

Secondary Endpoints: Overall SurvivalQuality of Life Health Economic AnalysisResponse RateToxicity/HypersensitivityDose Intensity Post progression therapy

Thank you for attention