NCCS Cancer Policy Roundtable Meeting Reinvigorating the Cancer - - PDF document
As Presented at the NCCS Cancer Policy Roundtable October 18-19, 2011 NCCS Cancer Policy Roundtable Meeting Reinvigorating the Cancer Clinical Research Enterprise Peter C. Adamson, M.D. The Childrens Hospital of Philadelphia Success Rates
As Presented at the NCCS Cancer Policy Roundtable October 18-19, 2011
Peter C. Adamson, M.D. The Children’s Hospital of Philadelphia
Adapted from Nature Reviews: Drug Discovery, 3 (8): 711, 2004
5% 11%
As Presented at the NCCS Cancer Policy Roundtable October 18-19, 2011
1950 1960 1970 1980 1990
CCG ECOG CALGB SWOG RTOG NWTSG GOG NSABP IRSG NCCTG POG
As Presented at the NCCS Cancer Policy Roundtable October 18-19, 2011
1955 1965 1975 1985 CCG
SWOG Pediat. Div.
NWTSG IRSG POG
CALGB Pediat. Div.
2000
N W Tumor S G
tudy ational ilms’ roup Rhabdomyosarcoma
INTERGROUP STUDY GROUP
Pediatric Oncology Group
As Presented at the NCCS Cancer Policy Roundtable October 18-19, 2011
As Presented at the NCCS Cancer Policy Roundtable October 18-19, 2011
Pre-Clinical Testing, R&D NDA Review Clinical R&D Post-Marketing Surveillance
Average 5 yrs (2-10 yrs) Average 24 mos (2 mos-7yrs)
Phase 1 Phase 2 Phase 3
Short-term Long-term
Average 18 mos (1-3 yrs)
Discovery Initial Synthesis & Purification Animal Testing Adverse Event Reporting Surveys Sampling Testing Inspections
IND 30 Day Safety Review NDA Submitted NDA Approved
FDA Time
Basic Resources Specialty Resources /Other
Phase I Program
(14 Phase 1 sites)
Pediatric Phase 1 Consortium CNS Consortia Pediatric, Adult Phase 2 Program
(10 Phase 2 sites)
Cooperative Groups *CCOPs
*Other (Centers, SPORES, R21, R01, P01, etc.)
*Non-CTEP Funded Resources RAID Phase 0 - NExT Expl IND
Courtesy of Jeffrey Abrams, MD NCI-CTEP
As Presented at the NCCS Cancer Policy Roundtable October 18-19, 2011
Pre-Clinical Testing, R&D NDA Review Clinical R&D Post-Marketing Surveillance
Average 5 yrs (2-10 yrs) Average 24 mos (2 mos-7yrs)
Phase 1 Phase 2 Phase 3
Short-term Long-term
Average 18 mos (1-3 yrs)
Discovery Initial Synthesis & Purification Animal Testing Adverse Event Reporting Surveys Sampling Testing Inspections
IND 30 Day Safety Review NDA Submitted NDA Approved
FDA Time
As Presented at the NCCS Cancer Policy Roundtable October 18-19, 2011
Time (Years) Clinical Development
Phase 1
Phase 2
Phase 3
Stdy D’vpt
Study Development
Rx
Process Takes up to 7 Years
National Cancer Institute Central IRB Re-Review Cooperative Group Response
Concept Approved Courtesy of David Dilts
As Presented at the NCCS Cancer Policy Roundtable October 18-19, 2011
Academia Industry
Scientific Review
As Presented at the NCCS Cancer Policy Roundtable October 18-19, 2011
Idea
Disease Committee Review
Cooperative Group Review
Concept
National Cancer Institute Central IRB Re-Review Cooperative Group Response
Concept Approved Courtesy of David Dilts
As Presented at the NCCS Cancer Policy Roundtable October 18-19, 2011
Sept-Oct 1998 Nov 1998 – July 1999 Aug 1999 - Present
As Presented at the NCCS Cancer Policy Roundtable October 18-19, 2011
As Presented at the NCCS Cancer Policy Roundtable October 18-19, 2011
Adapted from Nature Reviews: Drug Discovery, 3 (8): 711, 2004
5% 11%
As Presented at the NCCS Cancer Policy Roundtable October 18-19, 2011
Time (Years) Clinical Development
Phase 1
Phase 2
Phase 3
Stdy D’vpt
Study Development
Rx
As Presented at the NCCS Cancer Policy Roundtable October 18-19, 2011
*Placebo patients who progressed could cross over to sorafenib
†Including 36 patients without bidimensional tumor measurements, but with
radiological evidence of progression
Sorafenib 12-week run-in (n=202) Tumor shrinkage 25% (n=73) Tumor growth/ shrinkage <25% (n=69) Tumor growth 25% (n=51†) Off study (n=58) Sorafenib 12 weeks (n=32) Placebo* 12 weeks (n=33) Continue open- label sorafenib (n=79) % Progression free 24 weeks Disease status at 12 weeks unknown (n=9)
Courtesy of Mark Ratain, MD
Proportion of patients progression free
0.25 0.50 0.75 1.00
Time from randomization (weeks)
6 12 18 24 36 48 60 66 Sorafenib Placebo Censored
Median PFS Sorafenib = 24 weeks Placebo = 12 weeks Hazard ratio (S/P) = 0.44 p-value <0.000001
54 Courtesy of Mark Ratain, MD
As Presented at the NCCS Cancer Policy Roundtable October 18-19, 2011