NCCS Cancer Policy Roundtable Meeting

Transcription

1 NCCS Cancer Policy Roundtable Meeting Reinvigorating the Cancer Clinical Research Enterprise Peter C. Adamson, M.D. The Children s Hospital of Philadelphia Success Rates for Drug Development 11% 5% Adapted from Nature Reviews: Drug Discovery, 3 (8): 711,

2 NCI Cooperative Groups A Brief History History of NCI Cooperative Groups POG NCCTG IRSG NSABP GOG NWTSG RTOG SWOG CALGB ECOG CCG

3 History of NCI Cooperative Groups IRSG NWTSG SWOG Pediat. Div. CALGB Pediat. Div. POG CCG History of NCI Cooperative Groups Pediatric Oncology Group Children s Oncology Group INTERGROUP Rhabdomyosarcoma STUDY GROUP N ational Wilms Tumor S G tudy roup

4 Group Mergers ECOG ACRIN CALGB NCCTG ACOSOG RTOG NSABP GOG SWOG New Drug Development Timelines NCI Expanding Infrastructure 4

5 New Drug Development Timeline Pre-Clinical Testing, R&D Average 18 mos (1-3 yrs) Discovery Initial Synthesis & Purification Phase 1 Clinical R&D Average 5 yrs (2-10 yrs) Phase 2 Phase 3 NDA Review Average 24 mos (2 mos-7yrs) Post-Marketing Surveillance Adverse Event Reporting Surveys Sampling Testing Animal Testing Short-term Inspections Long-term IND 30 Day Safety Review NDA Submitted NDA Approved FDA Time CTEP Therapeutics Development Phase 1 Phase 2 Phase 3 Basic Resources Phase I Program (14 Phase 1 sites) Pediatric Phase 1 Consortium Phase 2 Program (10 Phase 2 sites) Cooperative Groups Specialty Resources /Other RAID Phase 0 - NExT Expl IND CNS Consortia Pediatric, Adult *Other (Centers, SPORES, R21, R01, P01, etc.) *CCOPs *Non-CTEP Funded Resources Courtesy of Jeffrey Abrams, MD NCI-CTEP 5

6 New Drug Development Timelines Clinical Trials New Drug Development Timeline Pre-Clinical Testing, R&D Average 18 mos (1-3 yrs) Discovery Initial Synthesis & Purification Phase 1 Clinical R&D Average 5 yrs (2-10 yrs) Phase 2 Phase 3 NDA Review Average 24 mos (2 mos-7yrs) Post-Marketing Surveillance Adverse Event Reporting Surveys Sampling Testing Animal Testing Short-term Inspections Long-term IND 30 Day Safety Review NDA Submitted NDA Approved FDA Time 6

7 Clinical Development Timeline Clinical Development Stdy D vpt Phase 2 Study Development Phase 3 Rx Phase 1 Time (Years) Concept to Trial Timeline Cooperative Group Response National Cancer Institute Central IRB Re-Review Concept Approved Process Takes up to 7 Years Courtesy of David Dilts 7

8 New Drug Development Timelines Investigator Perspective Academia Industry Scientific Review 8

9 Concept Incubation Idea Disease Committee Review Cooperative Group Review Concept Target Drug Patient Population Competing Ideas Research Landscape Scientific Mission Prioritization Resources Concept to Trial Timeline Cooperative Group Response National Cancer Institute Central IRB Re-Review Concept Approved Courtesy of David Dilts 9

10 Proposed New Organizational Structure of the Program Fail Early Sept-Oct 1998 Nov 1998 July 1999 Aug Present 10

11 I have not failed, I have just found 10,000 ways that won t work Thomas Edison Clinical cancer research needs a system that can strategically fail early 11

12 Cooperative Group Clinical Trials Efficient Effective Success Rates for Drug Development 11% 5% Adapted from Nature Reviews: Drug Discovery, 3 (8): 711,

13 Clinical Development Timeline Clinical Development Stdy D vpt Phase 2 Study Development Phase 3 Rx Phase 1 Time (Years) 13

14 Study Design: Patient Flow Tumor shrinkage 25% (n=73) Continue openlabel sorafenib (n=79) Sorafenib 12-week run-in (n=202) Tumor growth/ shrinkage <25% (n=69) Tumor growth 25% (n=51 ) Placebo* 12 weeks (n=33) Sorafenib 12 weeks (n=32) Off study (n=58) % Progression free 24 weeks Disease status at 12 weeks unknown (n=9) *Placebo patients who progressed could cross over to sorafenib Including 36 patients without bidimensional tumor measurements, but with radiological evidence of progression Courtesy of Mark Ratain, MD Progression Free Survival: Randomized Patients 1.00 Proportion of patients progression free Sorafenib Placebo Censored observation Time from randomization (weeks) Median PFS Sorafenib = 24 weeks Placebo = 12 weeks Hazard ratio (S/P) = 0.44 p-value < Courtesy of Mark Ratain, MD 14

15 Smart Trials Smart Drugs 15