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, 2007NCCCP Launch

1 Division of Cancer Treatment & Diagnosis2 Division of Cancer Prevention

Objectives

• Provide overview of NCI-sponsored clinical trials system

• Provide overview of clinical trials component of NCI Community Cancer Centers Program (NCCCP)

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

NIH Clinical Center in Bethesda, MDNCI’s Center for Cancer Research (CCR)

http://ccr.nci.nih.gov/

NCI’s CCR Clinical Trials

Treatment

SpecimenCollection

NaturalHistory

ImagingScreeningFollow-upPsychosocial

Epidemiology

Phase I

Phase II

Phase I/IIPhase III

Pilot

Of these treatment trials, breakdown by Phase

• 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

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)

• 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

• Currently sponsors over 140 INDsCurrently sponsors over 140 INDs

• Approx. 11,000 registered investigators Approx. 11,000 registered investigators

at over 3,300 institutionsat 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 Over 80 collaborative agreements

(CRADAs, CTAs, and CSAs) with (CRADAs, CTAs, and CSAs) with

pharmaceutical companiespharmaceutical companies

CTEP by Numbers

• 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

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

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

CTSU Cumulative Accrual by Study:As of May 31, 2007 – Top 14 Trials in Accrual (* = Metastatic Trial)

Trial # Title SiteNCIC-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 ACT vs AC vs ACT Breast

ACOSOG-Z9001 Imatinib vs Placebo GIST

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/

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)

• 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

Parts of the CCOP Program

CCOP MB-CCOP Research 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

Community Clinical Oncology Program

• Participating Physicians (3,385)– 2,170 Physicians Accrue Trial Participants

– 1,215 Physicians Refer Trial Participants

• Participating Hospitals (395)

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

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

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

NCCCP: Clinical Trials Components

Area Clinical Trial Component

1. Community InputLocal advisory board to advise & assist pilot w/ varied membership, assist to increase awareness of importance of CTs

2. Types of TrialsTypes include treatment, prevention, cancer control & symptom amelioration

3. Trial ComplexityTrial complexity: multimodality, phase 2, translational trials, referral to phase I ctrs

4. CT InfrastructureInfrastructure & 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

NCCCP: Clinical Trials Components

6. CollaborationsCollaborations w/ Ca Ctrs, CCOPs, Groups, Academia, Industry

7. Outreach to the Underserved

Programs and outreach for minorities & underserved to participate in trials

8. Accrual TrackingTrack patient accrual to trials and keep log of reasons why or why not pts go or don't go on trials

9. CommunicationSystem of communication of clinical trial availability: internal and external

Area Clinical Trial Component

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