Overview of the ETCTN May 30, 2015 Percy Ivy, MD ETCTN and ETCTN-Phase 1 Program Director Associate Chief, Investigational Drug BranchCancer Therapy Evaluation Program Goals and Objectives of the
Experimental Therapeutics Clinical Trials Network (ETCTN) Research and Development for New Treatments Dose and schedule in early treatment trials Novel combination therapies Tumor Characterization in Biomarker-driven studies Molecular characterization: expression, sequence and epigenetics Validated biomarker assays in qualified labs Functional imaging Enhanced understanding of cancer biology Bedside to bench and back Education and Training for young investigators Integrating NCI Drug Development Programs Nationwide ETCTN Phase 1 Principal Investigators
Institutions PIs City of Hope/Beckman Res. Inst. Newman, Edward Lenz, Heinz-Joseph Dana-Farber/Harvard Cancer Center Kufe, Donald Flaherty, Keith Shapiro, Geoffrey Duke U. North Carolina Wash. U. Hurwitz, Herbert Dees, Elizabeth Lockhart, Albert Johns Hopkins Carducci, Michael Gocke, Christopher Gojo, Ivana Rudek, Michelle Mayo - Rochester Erlichman, Charles Huluska, Paul Sausville, Ed NCI-DTC Kummar, Shivaani Institutions PIs Ohio State U. Grever, Michael Rutgers-Cancer Inst. NJ U. Wisconsin DiPaola, Robert Liu, Glenn U. Chicago Ratain, Mark Maitland, Michael U. Health Network Siu, Lillian Sullivan, Dan U. Pittsburgh Chu, Edward Beumer, Jan U. Texas MDACC U. Colorado Denver Yao, James Eckhardt, Gail Meric-Bernstam, Funda Yale University Lorusso, Patricia Eder, Paul Berlin, Jordan 4/26/2017 Clinical Translational Research and Cancer Biology: Bedside to Bench and Back *Clinical observations: Non-clinical models for targets Patients eligible for early phase clinical trials Clinicalresponse * Analysis of tumor and other tissues for pathway activation or biomarker Translational research with clinical models PK Sequencing Patient assigned to trial based on molecular characterization of tumor Methylation Functional imaging FISH * Tumor and normal tissue PD markers Patient monitoring IHC CTCs, CECs * Patient monitoring: Post-treatment molecular re-analysis for response/ resistance Expression array Tumor-initiating cells National Cancer Institute High Priority Targets and DCTD/CTEP Agents
IGF-1R Surface antigens ganitumab cixutuzumab linsitinib SGN 35 (CD30) HA 22 (CD22) CDX-011 bevacizumab ziv-aflibercept cetuximab HER2 Lapatinib Pertuzumab trastuzumab VEGF Notch RO other receptors EGF-R VEGF-R c-Kit Notch Hedgehog imatinib sunitinib sorafenib vismodegib sorafenib sunitinib cediranib pazopanib Met Raf Bcr tivantinib AMG337 cabozantinib rilotumuab Ras SRC Abl erlotinib AZD9291 dasatinib sorafenib dabrafenib ERa Stem cell signaling tipifarnib dasatinib saracatinib imatinib CDKs z-endoxifen PDGFR P13 K dinaciclib sunitinib imatinib pazopanib cediranib Microtubules PARP brentuximab vedotin veliparib BMN673 olaparib MK-2206 Akt PD1 MEK Btk Flt3,RET pembrolizumab nivolumab CHK1 bFGFR HDAC SCH iMID tramitinib selumetinib Aurora kinase A cediranib belinostat entinostat vorinostat BCR thalidomide lenalidomide pomalidomide AT-101 obatoclax navitoclax PCI-32765 MLN 8237 ibrutinib BCL-2 CD105 Wee1 kinase TORC MLN0128 temsirolimus Topoisomerases TRC105 MK-1775 CTLA44 Hsp90 LMP400/776 High priority targets and pathways go through NExT; NCI has a single pipeline. Broad portfolio for combination studies. Angiopoietins ipilimumab ticilimumab AT 13387 PU-H71 Alkylating AMG386 Dimethane sulfonate TL32711 XIAP mTOR IDO Proteasome 1-Methyl-[D]- tryptophan Methylation inh. bortezomib fenretinide FdCyd/THU TRC102 Ceramide Survival/ Proliferation Protein turnover Apoptosis Angiogenesis Immuno- modulation Migration/ invasion DNA repair epigenetics Mitosis Drug Development Project Teams Therapeutics Clinical
4/26/2017 NCI Team Science- Drug Development Project Teams Clinical (Experimental Therapeutics Clinical Trial Network) NCI Team Science - Drug Project Teams Centralized Support Translational Cancer Biology National Cancer Institute 7 New Development Cycle for NCI Experimental Therapeutics
1 NExT NCI Experimental Therapeutics INTRAMural Drug Project Team Clinical Translational Centralized Support Cancer Biology NCI Project Team Preliminary Drug Development Plan Division of Cancer Treatment And Diagnosis/ Cancer Therapy Evaluation Program meeting 2 Scientific Senior Advisory Committee Regulatory/ Agreements EXTRAMural Drug Project Team Drug and Assay/ Biomarker Development Plan Investigational Drug Steering Committee Review Scientific 3 Drug Project Team Clinical Translational Centralized Support Cancer Biology Projects Cooperative Research and Development Program- Development Cooperative Research and Development Program-Signed Regulatory/Agreements DCTD/CTEP 4 Senior Advisory Committee Letters of intent submitted Protocol development Protocol Activation DCTD Reviews Projects Challenges for the Early Phase Therapeutics Network
Accrual Smaller patient populations due to molecularly-defined diseases A scalable/flexible program that can rapidly adapt to accrual needs Biomarkers Often requires biopsies Fitfor purpose, validated assays Functional imaging More Facile Mechanisms for Translation To and From Bench to Bedside Collaborations More predictive animal models to evaluate tumor heterogeneity Agents currently tracked for PTA/PTMA
NSC/IND MOA CRADA* PTA/PTMA AT13387 749712/109876 Hsp90i 11/02/2009 Completed BMN 673 771561/119558 Oral PARPi 06/17/2013 AZD9291 781254/ EGFRi, 3rd Gen 09/29/2014 VX-970 780162/ ATRi 05/29/2014 In review SGI-110 780463/ DNMTi 12/11/2014 In prep AMG-337 779337/ cMeti 01/08/2015 Deve Stopped PD1 Immune Checkpoint i 07/15/2015* PDL1 MPDL3280 MEDI4736 783608 778709 NCI-Sponsored Infrastructure NCI-Sponsored Infrastructure for ETCN Trials Medidata Rave [Medidata Rave-focused webinar scheduled for April 28, 2014] Medidata Rave Web based EDC (electronic data collection) to be used in all future NCI studies CTEP-IAM account (user name and password) required to access Rave; must also have one of the Rave-specific roles. Users must also be on the ETCTN site roster of a participating organization and have approval for a given trial at their site to manage data in Rave. All ETCTN studies will use the same standard Theradex eCRFs resulting in expedited study set-up following approval Built-in, real-time edit checks will minimize queries and after-the-fact data cleaning Queries entered by CTMS monitors and auditors can be resolved within Rave by the site staff Web Reporting [Will be covered in a future focused webinar; TBD] On August 1, 2013, Paper Reports were retired!
Web Reporting Status On August 1, 2013, Paper Reports were retired! No more of this: Now you can generate reports like this: Enrollment Summary Adverse Events Contour Plot of Event Count
by Course and Grade Demographics Efficacy Summary ETCTN Education and Training
National Cancer Institute U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health 4/26/2017 ETCTN Education and Training Since program launch, we have held a number of educational webinars for ETCTN members: ForLeadership: Kick-off and Overview Rosters and Roles Patient Enrollment NCI CIRB PIO Updates Data Management Biomarkers Implementing Drug Project Teams Web Reporting For Site Staff: Introduction to the ETCTN, Centralized Services, and the CTSU Website Patient Enrollment Regulatory Processes Data Management National Cancer Institute Educational Materials
National Cancer Institute U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health 4/26/2017 Educational Materials Educational Materials on the ETCTN-CTSU website includes: links to the webinar recordings, checklists, and information sheets on 14 different topics : Protocol Development Protocol Amendments Person Registration & CTEP-IAM Rosters & Roles The CTSU Protocol Access & Communications Regulatory Processing The NCI CIRB Patient Enrollment Agent Ordering Data Management SAE Reporting CDUS Reporting Auditing and Monitoring All documents will be posted to the ETCTN pages on the CTEP website once development is complete National Cancer Institute National Cancer Institute
4/26/2017 National Cancer Institute U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Cancer Institute