1. CTEP Interactions with Industry and the FDA
Dale Shoemaker, Ph.D.
Sherry Ansher, Ph.D.
Regulatory Affairs Branch
Cancer Therapy Evaluation Program
CTEP.CANCER.GOV

2. Division of Cancer Treatment and Diagnosis
Office of the Director, DCTD
Biometric Research Branch
Radiation Research Program
Cancer Diagnosis Program
Cancer Therapy Evaluation Program
Developmental Therapeutics Program
Biomedical Imaging Program

3. Michaele Christian CANCER THERAPY EVALUATION PROGRAM
Clinical Grants and Contracts Branch
Roy Wu
CANCER THERAPY EVALUATION PROGRAM
Michaele Christian
Protocol and Information Office
Michael Montello
Clinical Investigations Branch
Richard Kaplan
Regulatory Affairs Branch
Dale Shoemaker
Investigational Drug Branch
Louise Grochow
Pharmaceutical Management Branch
Alfred Fallavollita
Clinical Trials Monitoring Branch
Joan Mauer

4. Theory to Therapy Our Mission
The mission of the Cancer Therapy Evaluation Program (CTEP) is to improve the lives of cancer patients by finding better ways to treat, control and cure cancer. CTEP accomplishes this mission by funding an extensive national program of cancer research and by sponsoring clinical trials to evaluate new anti-cancer agents, with a particular emphasis on translational research to elucidate molecular targets and mechanisms of drug effects.
Theory to Therapy

5. The Cancer Therapy Evaluation Program (CTEP)
Currently sponsors over 150 INDs.
9905 registered investigators at over 1950 institutions.
Over 1000 active protocols.
500 new protocols/year.
~25,000 patients accrued/year.
Over 80 collaborative agreements (CRADAs, CTAs, and CSAs) with pharmaceutical companies.

6. Investigational Anticancer Agents Clinical Investigators
Doing Battle Against Cancer - A Collaborative Effort
Pharmaceutical/Biotech Company
Pilot studies and pivotal trials leading to licensing
DCTD-NCI
Expedite pivotal trials
Exploratory studies
Other indications (tumor types)
Combination regimens of investigational agents from two or more sources
Alternative methods of drug administration
Investigational Anticancer Agents
Clinical Investigators
IND and Clinical Trials
Novel Cancer Therapies

7. Collaborating with CTEP
The Advantages of
Collaborating with CTEP
CTEP Sponsors INDs.
CTEP provides a wide range of investigational agents for clinical trials in a variety of tumor types and disease settings.
Indemnification issues are addressed in collaborative agreements.

8. Regulatory Affairs Branch
Prepares and submits Investigational New Drug Applications (INDs).
Reviews protocol LOIs, protocols, and protocol amendments.
Liaison with FDA.
Liaison with intramural and extramural investigators.
Interacts with biotech and pharmaceutical companies.
Prepares agreements for clinical development of agents.
Coordinates company interactions with NCI and NCI investigators.

9. Clinical Grants and Contracts Branch
Serves as the contact for extramural investigators for administrative and scientific advice concerning clinical research grants, cooperative agreements and contracts.
Manages three Grant Programs in Clinical Oncology, Surgical Oncology, and Cancer Nutrition.
Continued

10. Clinical Grants and Contracts Branch
Supports grants and cooperative agreements encompassing clinical agent development at the molecular, cellular and whole body levels as well as treatment regimen and methodology development.
Participates in the planning, implementation, and management of the early phase clinical trials contract and cooperative agreement programs, the Clinical Trials Cooperative Groups.

11. Source of Agents for CTEP
Agents developed at NCI.
Agents developed under NCI-funding agreements.
Agents developed independently by universities or other academic or research institutions.
Agents developed by biotech and pharmaceutical companies.

13. CTEP Activities as IND Sponsor
Pre-IND Meetings with FDA
IND Filing
Protocols and Amendments
Monitoring of and reporting to FDA on adverse drug events
Annual Reports to FDA
Responses to FDA letters and phone inquiries
Attendance and participation at meetings
Requests to export agents to foreign investigators
Participation in joint NCI-FDA sponsored conferences

14. Guidelines for NCI-Sponsored Trials
NCI holds MF for all sites/investigators
NCI approves all protocols
Investigators must adhere to protocols
Confidentiality and transfer limitations apply
Institutions maintain ownership of investigator data and intellectual property
Access to data provided to NCI and collaborating company(ies)

15. The Clinical Trials Cooperative Groups
Established in 1955 to test new cancer therapies and funded as grants
Support mechanism changed to cooperative agreements in 1980 to highlight NCI’s participation in the program
Funding for the group is a specific line item in the NCI budget that does not compete with the RPG pool
Currently 12 groups which are funded by over 150 U10s and which receive about $125 million

16. Clinical Trials Through the Cooperative Groups
Conduct large multi-center trials
Funding is independent of any specific trial and is mainly for data management
Group structure consists of a headquarters / operations office, a biostatistical/data management office and the participating institutions
Many of the institutions are funded as subcontracts by the operations office for enrolling patients
Groups seek industry support for trials of high scientific merit to offset some of the costs not covered by funding
Insurance companies are reimbursing some of patient care costs on group studies

17. Clinical Trials Provisions for All CTEP Cooperative Agreements
IND sponsorship
Drug Supply
Adverse Event
Reporting
Protocols
Monitoring
Data Rights
Publications
Patents
CTEP
NCI

18. Collaborating with CTEP
The Advantages of
Collaborating with CTEP
Regulatory expertise.
Ability to evaluate agent in wide variety of tumor types and disease settings.
Expedite trials through extensive clinical trials network of cooperative groups, cancer centers, and phase 1 & 2 contracts.
Primary data concerning a particular agent are made available exclusively to NCI collaborator for that agent.

19. Clinical Trials Agreement (CTA)
A CTA may be appropriate when:
Collaborator has strong patent position
Collaborator has completed preclinical studies and IND-directed toxicology
Collaborator will supply agent only

20. Cooperative Research and Development Agreement (CRADA)
Detailed agreement between the NCI and a pharmaceutical company (Collaborator) for the clinical co-development of an agent that:
 usually stipulates terms for a much broader scope of research than a CTA.
 usually encompasses preclinical development
 usually includes funds from collaborator

21. Collaborative Clinical Development of Agents - INDs
Either NCI or collaborator will submit an IND
Either may cross-reference an IND or Master File (MF) held by the other
All information in INDs will be fully shared between NCI and collaborator
Manufacturing data may be held confidential by collaborator

22. Timely access to clinical trial data.
Collaborative Therapeutics Development Between NCI and Industry - Issues and Challenges
Patent rights.
Data rights.
Timely access to clinical trial data.
Control and timely completion of clinical studies.
Publications.
Combination of investigational agents.

23. Patent Rights
Terms of award to clinical sites include Intellectual Property Option to collaborator. This offers rights of first negotiation to collaborator who supplied Agent if there is an invention.
Co-exclusivity for combination studies.

24. Data Rights
Primary data generated in NCI-sponsored clinical trials are made available exclusively to NCI and the Collaborator. The FDA has the right to review the data.
Provisions included in terms of award and standard language in all protocols.

25. Timely Access
CTEP is implementing a new electronic web-based clinical trials reporting system which should improve the speed with which data are available to Collaborators.
Arrangements are made to provide Collaborators with access to trial data through existing systems such as CDUS.

26. Control Over Agent
Clinical development is a collaborative effort between the NCI and the Collaborator. All protocols are mutually agreeable to the NCI and the Collaborator.
Drug development plans are established jointly so that needs and interests of both parties are addressed.
All protocols are reviewed by CTEP and collaborators.

27. Publications
Collaborators are given 30 days to review manuscripts prior to submission to assure that no confidential/proprietary information is released.
An additional 30 days can be requested for patent filings only.
Purpose: information but not censorship.
Meeting Abstracts are sent as a courtesy to Collaborator prior to, or at the time of submission.

28. Current Initiatives at CTEP
Data reduction.
Preparation for the electronic filing of protocol, and e-INDs.
Adverse Events Expedited Reporting System (AdEERS).
Clinical Data Update System (CDUS).
Expanded Participation Project.
Clinical Trials Support Unit.

29. CTEP on the Web - CTEP.CANCER.GOV
Program information.
Informatics initiatives - AdEERS, CDUS.
Model agreements - CDA, CTA, CRADA and CRADA appendices.
Standard protocol language - all protocols using an investigational agent supplied under a CTA or CRADA must incorporate the standard language which details publication rights, data access, and intellectual property.
Terms of award option to collaborator for intellectual property.