Post on 12-Aug-2019
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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