Early Clinical Trial Unit and Clinical Trial Highlights

Prof. Dr. Monika EngelhardtProf. Dr. Justus DuysterHematology & Oncology

Early Clinical Trial Unit UKF - CCCFKey goals

• To promote substantial therapeutic progress in cancer patients, byinnovative agent testing and therapeutic strategies

• To assess novel agents after preclinical testing in patients for safetyand best tolerance (phase I) as well as efficacy (phase II)

• To provide a highly specialized unit with intensive, expertise clinicalcare, monitoring and data analysis support for patients who receivenovel agents (first in man trials).

Early Clinical Trials Unit (ECTU) of the CCCF satisfies these needs(cost-neutral; to be finalized in Central Medical Clinic Building 12/2012)

Source: DRKS, CCCF-parameters in DRKS, ethics committee Freiburg, 10.09.2012(date/year based on recruitment information, if not available, date of the Freiburg-ethics committee approval was used )

Clinic UKF CCCF Organ Center/DevisionHematology & Oncology 14 14 Leukemia, Lymphoma, Myeloma, ZTTGastroenterology 6 6 ZGTPediatric Hematology & Oncology 6 6 Pediatric OncologyThoracic surgery 2 2 ZTTOphthalmology 2Infectious diseases 1Pneumology 1 1 PneumologyNuclear medicine 1 1Gynecology 1 1Radiation Therapy 1 1 Head & NeckNeurology 1Pediatric medicine 1

Total 37 32

UKF Early Clinical Trials2010 - 5/2012

Early Clinical Trials - Hematology & Oncology

05

101520253035

Phase

I , I/I

I

Phase

II

Phase

III

Other

2008200920102011

Phase I, I/II Phase II Phase III Other ∑# of CTs 10 30 27 12 79# of included pts 27 147 45 102 320Pt-# / CT 2.7 4.9 1.7 8.5 4.1

Data CTs 2011: # of CTs, # of pts and pt-# / CT

Number (#) of phase I / I/II, II, III and other clinical trials (CTs), 2008-2011

# of Clinical Trials Med 1 / disease entity, 2011

7GI

22Lymphoma

24MDS n=7AML n=13ALL n=4

MDS, AML, ALL

4Other1Sarkoma6NSCLC

6MPN

9auto n=2allo n=7SCT

∑ CTsSubentitiesEntity

Phase I/II trials in solid tumors, Med. I

1503/2010(end of

recruitment: 04/2012)

noI/II1Stage III/IVNSCLCCilengitide, Cetuximab, Gemcitabine, Cisplatin6301

company'sdecision of trial on hold

01/2010 (end of recruitment:

05/2011)noI/II2relapsed/

refractoryColorectalcancerCetuximab + Irinotecan6916

607/2011-noI/II≥1Stage II-IVPancreaticcancer

Gemcitabine ±Chk1 inhibitor7604

0long CTx-

pauserequired,

CT-scans to be US-

assessed

10/2007-2010noII>1Platin-CTxrefractoryHead&NeckZalumtuzumab5947

308/2011 (end of

recruitment: 12/2011)

yesIb/II>1Platin-CTxrefractoryNSCLCEribuline Mesylate +

Pemetrexed7173

Surgery dep.since: 07/2010noII≥1resectablemetastasticGI

Folfox ± Cetuximabperioperative CTx6745

52007-2010noI/II1Stage III/IVNSCLCPemetrexed, Carboplatin ±Sorafenib5492

Tumor-entity# Start of recruitment

Recruitedpts in

FreiburgLead FreiburgPhaseLinePt-group

inclusionTrial-specific therapeuticcombination

Int. trial#

Clinical Cancer Research Group Freiburg 10/2012

Phase I/II Trials, Med 1, 2012

28/2012noI->IIa>1relapsed/refractoryrMMNOX-A12 (SDF1-Antagonist)7762

3110/2007yesI/II-GvHDallo-SCTEverolimus + Myofortic5573

in preparationstart I.q/2013

yesI/II>1relapsed pts afterallo-SCTAMLTreosulfan-Fludarabin-TT

cond. for 2.allo-SCT7977

in preparationstart I.q/2013yesI/II>1relapsed/refractoryAML + high-

risk MDSATRA ± Tranylcypromin8068

610/1999

(recruitment stop: 09/2012)

yesI/II1Solid tumorsallo-SCTRelated allo-SCT w FC1784

in preparationstart I. q/2013noI/II>1relapsed FL.Follicular

lymphomaLen + Ritux ± Benda 80511

in preparationstart IV.q/2012noI/II≥1High-risk, relapsed

ptsMMRIC in allo-SCT fromunrelated donors7799

102/2012noI/II1high risk of induction failureAML

Cytarabin, Idarubicin, Clofarabin(CIARA-trial)

7506

702/2010noI/II1newly diagnosedCBF AMLAML

Dasatinib in induction-, consolidation and maintenance(AML SG 11-08)

6595

908/2011yesI/II>1relapsed/refractoryMultiple Myeloma (MM)

Vorinostat, Bortezomib, Doxorubicin, Dexamethason(VBDD-trial)

6581

DLBCL

Tumor entity

in preparationstart IV.q/2012noI/II≥1relapsed/refractoy

Temsirolimus, Rituximab and DHAP(STORM-trial)

76310

# Start of recruitmentPatient #

recruited in Freiburg

Freiburg leadPhaseLineIndicationAssessment ofInt. Trial-#

CCR-group Freiburg, 10/2012

TKI Trials, Med 1

in preparationnoIII1Ph+/Abl+CMLNilotinib induction, Nilotinib or a-IFNmaintenance (Tiger)

77110

09//2009

(recruitment stop: 4/2011

noIII1unresectable orrefractoryGISTNilotinib vs. Imatinib6521

19/2009

(recruitment stop: 2/2011

noIII>1Imatinib and Sunitinib-resistantGISTNilotinib6542

188/2011

(recruitment stop8/2012

noIII1post PVOMFJump7483

38/2011

(recruitment stop12/2011)

noI/II>1Ph+ +/- Bcr/ablCMLEnest7137

in preparationno1CMLPonatinib cs. Imatnib8018

3noIII1Ph+, CPCMLImatinib vs. standardtherapy2154

in preparationno≥1GISTMasatinib vs. Sunitinib8049

3(recruitment stop: 1/2011)noIII>1Expanded AccessCMLPegasys4916

52008noIII>1Imatinib-resistantCMLCML 4 Nilotinib6265

Tumor entity# Start of recruitment

Patient # recruited in

FreiburgFreiburg leadPhaseLineIndicationAssessment ofInt.

Trial-#

CCR-group Freiburg, 10/2012

•Safety and efficacy of NOX-A12 in combination with Bortezomib and Dexamethasone in previously treated MM pts•MM-register: MM-comorbidity-, CI-, SAE-assessments•EBMT: Prognostic score in MM pts receiving ASCTs•Health Service Research: Futura-MM-analysis

•Pomalidomid + Elotuzumab (relapsed/ref. MM)•EMN Multi-center RIC-allo-Tx for high-risk relapsed pts•EMN randomized phase 2 study in elderly newly diagnosed MM, w proteasome inhibitor MLN-PDN vs. MLN-Cyclo vs. MLN-PDN-Bendavs. MLN-PDN-Thal, followed by maintenance random: MLN vs. placebo•EMN: Carfilzomib + Benda (IIT-Rezidivprotokoll, Kiel)

DSMM XIV

Clinical studies in Multiple Myeloma

Ph I/II

Ph I/II

Ph I/II

Ph I/II

Trial discussion and acceptance modus

Adequate pt # at UKF?-> eTBD search

Competitive, activetrials?

Regulatory and financial aspects?

Protocol Study Review Board (PSRB)(Head of the department; Attending physicians; PIs; CCR-Group)

Harmonized, 'democratic' decision on trial acceptance

Relevant scientifictrial question(s)?

1. PSRB meeting Med 1: 2004# of PSRB 1/2004 - 10/2012: 58

Section planEarly Clinical Trial Unit, Leukapheresis + Clinical

Cancer Research Group

Leukapheresis (LP)/ECP

LP/ECP(barrier nursing)

Phase I/II / LPMonitoring

Phase I/II

Outpt. clinic

roomPhase I/II / LP SN II

SN ISecretary

Studylogistics/coordination Tum

or Base Docum

entation

CTx-Safety/Pharmacology support

AttendingECTU

AttendingLP

Monitoring

Staff/recreation/meeting

room

Refrigerators,

Centrifuges, etc.

Storage

Conference

room

Early Clinical Trial Unitand associated capacities (enlargement I)

Leukapheresis (LP)/ECP

LP/ECP(infectious pts/barrier nursing)

Phase I/II / LPMonitoring

Phase I/II

Oupt. clinic roomPhase I/II / LP

Study

Nurses

Early Clinical Trial Unit, Leukapheresis + ClinicalCancer Research Group (enlargement II)

Leukemia w

ard 'Holthusen'

Studylogistics/coordination

Secretary

Tumor B

ase Docum

entationCTx-Safety/

Pharmacology supportAttending

ECTUAttending

LP

Monitoring

Lab.: Refrigerators,

Centrifuges, etc.

Storage

Conference

room

Cost-neutral realized structures for phase I/II clinicaltrials

• 6 - 8 beds (3 for outpatient care in new ECTU, 3-5 inpatient beds on leukemia ward 'Holthusen')

• Study nurse support, study coordination, monitoring, chemotherapy-management, pharmacology, tumor-base-documentation are all integratedin new unit

• Medical equipment is available (monitors, infusion pumps, ECG, emergency equipment)

• Clinical trial-specific equipment is in place (centrifuges, refrigerators, studymedication storage room, monitoring and study audit capacities)

• Outpatient capacity• Combined organization of phase I/II + LP + Clinical Cancer Research

Group to a personnel-efficient unit• In close proximity to leukemia ward (Holthusen, 24 h physician support)• Central location + easy access to intensive care unit

-> Central unit for all oncology-active departments/clinics forproficient ECTU performance

Staffing ECTU / LP / CCRG team

Present personnel structure ECTU/LP/CCRG:

• Oncology attendings (2)• Physicians (1-2)• Study Nurses (5)• TB documentation (1,5)• Study coordination (1)• Pharmacists (2)

(CTx-management / study support)

• Study/TBD assistants (WiHi; 5)

• MTA (1)• Biometry (1,5)• PhD position (Pharmacist)• Secretary (1)

Requirements phase I/II core team:

à 1 Study Nurse

(Med I / Clinical trial Unit UKF)

(Clinical pharmacologist)

Budget p.a.: 300 T€ - 350 T€Additional personnel will be recruitedproject-/CT-related (e.g. Clinical Trials Unit UKF [Studienzentrum])

Opportunities and prospects of UKF phase I/II CCCF

• As a central unit, the ECTU allows translational clinical research and further improves oncology investigations for the UKF

• Logistic and structural requirements for the expertise performance of early clinical trials with study-knowledgeable personnel for outpatientand inpatient treatment

• Enables all oncology-active departments/clinics within a interdisciplinary platform to perform phase I and I/II trials

• Fulfills all requirements for phase I and II clinical trials, also as a proficient partner for pharmaceutical companies*

• Is integral part of the CCCF and is directed in close collaboration withthe CCCF-associated members

• Leadership and organisation: Prof. Dr. Monika Engelhardt

* Industry cooperations:Novartis: OTM certification 1/2013

Roche: in dialogePrefered partners: entire UKF and South-West region, Quintiles, Oncotest