1. NCI-Sponsored Clinical Trials Andrea Denicoff, RN, MS, ANP 1 Worta McCaskill-Stevens, MD 2 Jo Anne Zujewski, MD 1 Jeff Abrams, MD 1 June 25, 2007 NCCCP Launch 1 Division of Cancer Treatment & Diagnosis 2 Division of Cancer Prevention

2. Objectives Provide overview of NCI-sponsored clinical trials system Provide overview of clinical trials component of NCI Community Cancer Centers Program (NCCCP)

3. NCI-Sponsored Clinical Trials: Intramural & Extramural Intramural clinical trials – Conducted by scientists employed by the Federal government – Physicians, scientists, nurses, social workers, etc. – Clinical Trials conducted on NIH main campus Extramural clinical trials – Conducted by scientists who have been awarded grants through the NIH grant program – Clinical trials conducted around the U.S. and in some foreign countries

4. NIH Clinical Center in Bethesda, MD NCI’s Center for Cancer Research (CCR) http://ccr.nci.nih.gov/

5. NCI’s CCR Clinical Trials Of these treatment trials, breakdown by Phase

6. NCI-Designated Cancer Centers Program Division of Cancer Treatment & Diagnosis –Cancer Therapy Evaluation Program (CTEP) Clinical Trials Cooperative Group Program –Cancer Imaging Program American College of Radiology Imaging Network (ACRIN) Division of Cancer Prevention –Community Clinical Oncology Program (CCOP) –Minority-Based CCOP NCI-Sponsored Clinical Trials: Extramural

7. http://cancercenters.cancer.gov/ NCI Designated Cancer Centers Program Research areas Basic research Clinical research Prevention, Control, Population/Behavioral Sciences Comprehensive Cancer Centers (39) Integrates research activities across all 3 major areas Cancer Centers (24) Scientific agenda focuses on any one or two research areas Total Centers (63)

8. NCI-Designated Cancer Centers Program Division of Cancer Treatment & Diagnosis – Cancer Therapy Evaluation Program (CTEP) Clinical Trials Cooperative Group Program –Cancer Imaging Program American College of Radiology Imaging Network (ACRIN) Division of Cancer Prevention –Community Clinical Oncology Program (CCOP) –Minority-Based CCOP NCI-Sponsored Clinical Trials: Extramural

9. Currently sponsors over 140 INDsCurrently sponsors over 140 INDs Approx. 11,000 registered investigators at over 3,300 institutionsApprox. 11,000 registered investigators at over 3,300 institutions Over 1000 active protocolsOver 1000 active protocols 500 new protocols/year500 new protocols/year Approx. 33,000 patients accrued/yearApprox. 33,000 patients accrued/year Over 80 collaborative agreements (CRADAs, CTAs, and CSAs) with pharmaceutical companiesOver 80 collaborative agreements (CRADAs, CTAs, and CSAs) with pharmaceutical companies CTEP by Numbers

10. Cooperative Group Program (the “Groups”) is distinctive among NIH-supported clinical trials programs: –A clinical trials infrastructure that is continuously available to test new therapeutic strategies –Consists of researchers at institutions affiliated with the Groups who jointly develop and conduct trials in multi-institutional settings –Flexible research agenda allows change of strategy in response to changing scientific opportunities and new discoveries NCI-Sponsored Clinical Trials Cooperative Groups

11. NCI Cooperative Groups 10 Groups - 9 adult and 1 pediatric Multimodality: Cancer and Acute Leukemia Group B (CALGB) Eastern Cooperative Oncology Group (ECOG) North Central Cancer Treatment Group (NCCTG) Southwest Oncology Group (SWOG) NCI of Canada – Clinical Trials Group (NCIC-CTG)** Specialty: American College of Surgeons Oncology Group (ACOSOG) National Surgical Adjuvant Breast & Bowel Project (NSABP) Gynecologic Oncology Group (GOG) Radiation Therapy Oncology Group (RTOG) Children’s Oncology Group (COG) ** NCIC-CTG funding limited to participation in Intergroup trials

12. Scope United States and Canada –International Sites of US Groups Phase 3 adult cancer tx trials –Breast, GI, GU, GYN, Head & Neck, Leukemia, Lung, Lymphoma, Sarcoma, others Selected Phase 2 adult cancer tx trials Over 65 active trials for adults with cancer Over 22,000 enrollments since 1999 www.ctsu.org

13. CTSU Cumulative Accrual by Study: As of May 31, 2007 – Top 14 Trials in Accrual (* = Metastatic Trial) Trial #TitleSite NCIC-MA.27 Exemestane vs Anastrozole Breast CALGB-40101 CA (4 vs 6 cycles) vs Paclitaxel (4 vs 6 cycles) Breast NSABP-B-39 Whole Breast Irradiation vs Partial Breast Irradiation Breast NSABP-B-38 TAC vs DD AC-P vs DD AC-PG Breast N0147 mFOLFOX6 vs mFOLFOX6 + Cetuximab Colon PACCT1 TailoRx (Onco-Type DX) Breast NSABP-B-35 Anastrozole vs Tamoxifen in DCIS Breast S0221 Contin. AC+G vs Q 2 wk AC->P (Q 2 vs Q 12 wks) Breast IBCSG-25-02 Role of Exemestane Plus GnRH Analogue Breast IBCSG-24-02 Role of Ovarian Function Suppression & Exemestane Breast NSABP-C-08 mFOLFOX6 vs mFOLFOX6 + Bevacizumab Colon C80405 Chemo/BV vs Chemo/C225 vs Chemo/BV/C225 *CRC NSABP-B-30 AC  T vs AC vs ACT Breast ACOSOG-Z9001 Imatinib vs Placebo GIST

14. What types of trials? Focus on developing treatment approaches Integrate new agents into standard regimens Compare two or more novel approaches to an accepted standard Multimodality treatments Emphasis on incorporating correlative sciences, banking tissues and quality of life Uncommon diseases or less common presentations of common diseases http://ctep.cancer.gov/

15. Selected NCI/CTEP-sponsored Group Trials Contributing to FDA-approved Indications for New Oncology Agents 1991 –Fludarabine phosphate (SWOG) –Pentostatin (CALGB, SWOG) 1992 –Paclitaxel (GOG, CALGB, ECOG, NCCTG, SWOG) 1993 –Melphalan IV (CALGB) 1994 –Pegaspargase (POG) 2001 –Imatinib mesylate (COG, SWOG) 2004 –Letrozole (NCIC, Intergroup) –Oxaliplatin (NCCTG, Intergroup); –Taxotere (SWOG) 2005 – Nelarabine (COG, CALGB) 2006 –Bevacizumab (ECOG, Intergroup); Rituxin (ECOG, Intergroup) –Herceptin (NSABP, NCCTG, Intergroup)

16. NCI-Designated Cancer Centers Program Division of Cancer Treatment & Diagnosis –Cancer Therapy Evaluation Program (CTEP) Clinical Trials Cooperative Group Program –Cancer Imaging Program American College of Radiology Imaging Network (ACRIN) Division of Cancer Prevention – Community Clinical Oncology Program (CCOP) – Minority-Based CCOP NCI-Sponsored Clinical Trials: Extramural

17. Parts of the CCOP Program CCOPMB-CCOPResearch Base Consortia of Hospitals & Practices that accrue patients to NCI trials Institutions with >40% minority cancer patients that accrue to trials Cooperative Groups Cancer Centers Design & conduct cancer control & prevention clinical trials

18. Community Clinical Oncology Program Participating Physicians (3,385) – 2,170 Physicians Accrue Trial Participants – 1,215 Physicians Refer Trial Participants Participating Hospitals (395)

19. Community Clinical Oncology Program Impact of CCOP Participation in Treatment – 122,910 Patients on Treatment Clinical Trials – 1/3 Accrual to Cooperative Group Treatment Trials – Results from Treatment Trials are Directly Applicable to Patients in Their Communities – Community Physicians Who Participate in Trials More Rapidly Adopt State-of-the-Art Treatment

20. Community Clinical Oncology Program Impact in Prevention – Over 93,380 Persons at Risk for Cancer on Prevention Clinical Trials – CCOP Network Is the Vehicle to Conduct Phase III Cancer Prevention Trials (all of which are peer reviewed) – Community Physicians Practices Are the Forefront for Cancer Prevention

21. NCCCP: Clinical Trials Key Components Types of Clinical Trials –Treatment –Cancer Control and Symptom Reduction –Prevention Complexity of Trials –Phase 2 and 3 –Multimodality capacity (i.e., RT+ surgery) –Ability to do translational type trials (specimen submission-rich) Connections to the Community –Ca Ctrs, Academic Ctrs, CCOP/MBCCOPs, Coop Groups, Industry –Referrals for phase 1 –Emphasis on Minority Accrual

22. NCCCP: Clinical Trials Components Area Clinical Trial Component 1. Community Input Local advisory board to advise & assist pilot w/ varied membership, assist to increase awareness of importance of CTs 2. Types of Trials Types include treatment, prevention, cancer control & symptom amelioration 3. Trial Complexity Trial complexity: multimodality, phase 2, translational trials, referral to phase I ctrs 4. CT Infrastructure Infrastructure & staff dedicated to working on clinical trials, education for new staff 5. Protocol Activation Timeliness Track protocol receipt to activation, develop a log to measure timelines

23. NCCCP: Clinical Trials Components 6. Collaborations Collaborations w/ Ca Ctrs, CCOPs, Groups, Academia, Industry 7. Outreach to the Underserved Programs and outreach for minorities & underserved to participate in trials 8. Accrual Tracking Track patient accrual to trials and keep log of reasons why or why not pts go or don't go on trials 9. Communication System of communication of clinical trial availability: internal and external AreaClinical Trial Component

24. NCCCP Research Questions: Reducing Barriers to Clinical Trial Participation Ineligibility by disease, trial type, common cross-trial factors, gender, others Minority accrual issues – barriers, new research issues from the community Physician participation – reasons some docs don’t participate, don’t randomize, won’t refer CIRB utilization – if yes, how is it working? – and if no, why? Phase 2 studies – problems & solutions