Step 1: Developing a Cancer Prevention Clinical Trial
Protocol Development
The chemoprevention Phase I and II consortia must submit Letters of Intent for review and approval prior to the submission and review of the protocol.
Letter of Intent (LOI) Process
The chemoprevention Phase I and II consortia must submit Letters of Intent for review and approval prior to the submission and review of the protocol.
DCP will solicit Letters of Intent from investigators who want to conduct clinical trials with specific agents.
Agent Announcement:
- DCP will periodically announce agents available for Phase I or II clinical trials. The agent announcement will be sent to the consortium principal investigators via e-mail from the DCP Protocol Information Office (PIO).
- The frequency of the agent announcements is anticipated to be on a quarterly basis depending on agent availability and program priorities.
- Consortia members will respond to agent announcements by submitting a LOI to the DCP PIO. The LOI process allows the investigator to have a study concept/design reviewed and approved by DCP prior to the preparation and submission of a formal protocol document.
- Consortia members may also submit unsolicited LOIs.
LOI Deadline:
- Deadlines for LOI submissions will be 45 days after DCP announces the request for LOIs.
- DCP will review unsolicited LOIs when agents are available after solicited LOIs have been reviewed or if investigators have access to agents from non-DCP sources.
LOI Submission:
- The investigator will email the LOI Submission form (version 6.0) (doc, 81kb) to the DCP Protocol Information Office in conducting a particular clinical study.
- For any proposed trial, the investigator will document the ability to accrue the required number of study participants within a reasonable time period.
- When collaborations are planned, letters of collaboration with documentation of accrual will be required.
- Statistical design issues will be addressed in the LOI as well as the research plan for the laboratory analyses.
- The investigator will submit a description of and a budget for laboratory biomarker analyses and associated research costs for the correlative translational studies with each LOI.
- The investigator will provide evidence of capability to carry out the proposed studies/analyses (including IT capability, use of appropriate lab data models and systems).
LOI Review:
- The DCP LOI Review Committee will review LOIs within 4 weeks after the submission deadline has passed or 4 weeks after receipt of the unsolicited LOIs.
- The DCP LOI Review Committee may disapprove, approve or approve with recommended or required changes.
Questions regarding the use of the templates or submission of documents may call the DCP Protocol Information Office at (301) 496-0090.
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Protocol Process
Protocol Development and Submission:
- Protocols should be developed using the DCP Consortia Protocol Template, Version 3.4 (doc, 320kb).
- The protocol will address all issues raised in the LOI approval letter.
- The investigator should provide a rigorous description of the rationale and methodology for the laboratory components of the study as well as a description of how the results will be analyzed in conjunction with the results of the clinical trial for the translational studies.
- Within 60 days after notification of approval of the LOI, the investigator will submit the clinical protocol with informed consent. At the same time, Additional Study-Related Documents (doc, 142kb), which includes the CRFs, along with a detailed budget must be submitted electronically to the DCP Protocol Information Office (PIO) at NCI_DCP_PIO@mail.nih.gov.
- Incomplete protocols will be returned to the investigator without review.
Protocol Review:
- The DCP Protocol and Safety Review Committee (PSRC) will review protocols within 4 weeks of receipt by the DCP PIO.
- The PIO will send the Consortium Principal Investigator a Consensus Review indicating review outcome and required or recommended changes within 2 weeks of review.
- If changes are requested, the investigator submits a revised protocol within the deadline indicated on the Consensus Review (usually within 4 weeks).
- Revised protocols should be accompanied by a cover letter that addresses each DCP comment point-by-point.
- Revised protocol submissions should include the DCP Consortia Protocol Submission Worksheet Version 4.0 [pdf (35kb) | doc (130kb)] the cover letter with point-by-point responses, a highlighted and a clean copy of the protocol document.
- The approved protocol will be submitted to the FDA by DCP for all DCP-sponsored IND studies.
- All protocols submitted to the FDA require a 30-day wait for FDA comment.
Protocol Activation:
- Studies may only be activated following NCI and IRB approval and reciept of agent.
- Budgets for protocol-specific costs will require prior Contract Officer Approval (COA) before the investigator can begin to incur costs for that protocol.
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Study Design
Available information on study design includes:
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Resources
The Chemopreventive Agent Development Group supports Phase I chemoprevention trials.
These organ specific research groups support Phase II chemoprevention trials:
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Informed Consent
The DCP Chemoprevention Informed Consent Template (doc, 102kb) should be used for the chemoprevention studies. Informed consent models and information can be obtained from:
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Developing Case Report Forms
Case Report Forms should be developed using:
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Monitoring Plan
A Monitoring Plan consists of two components:
- Data and Safety Monitoring Plan - defines the process to ensure and maintain the scientific integrity of human subject research and to protect the safety of human subjects. NIH Guidelines (1998) specify that all clinical trials should have in place a system for appropriate oversight and monitoring to ensure the safety of participants and the validity of the data.
- Multi-Institutional Monitoring Plan - focuses on overseeing the progress of a clinical trial and ensuring that it is conducted, recorded, and reported in accordance with the protocol, Standard Operating Procedures (SOPs), Good Clinical Practice (GCP) guidelines, and the applicable regulatory requirements.
Data and Safety Monitoring Plan (DSMP):
- A Data and Safety Monitoring Plan (DSMP) will be submitted for each protocol to DCP for review and approval prior to study initiation.
- An Institutional Review Board and National Cancer Institute approved institutional plan may be referenced, however, it must appropriately address any unique needs of the chemoprevention trial.
Multi-Institutional Monitoring Plan (MIMP):
- Multi-Institution studies will be conducted according to the DCP Multicenter Guidelines.
- The MIMP must be submitted within 30 days following the contract award.
- The MIMP must be referenced in each protocol and any protocol-specific changes to the MIMP must be added.
- The Consortium Principal Investigator at the Lead Organization should present a plan to monitor, audit, and ensure the quality of the data from any Participating Organizations.
- The Consortium Principal Investigator at the Lead Organization should present a plan to provide study-related information and education to all sites.
- The Lead Organization and the Participating Organizations must have an appropriate assurance on file with the Office of Human Research Protection (OHRP).
- The protocol will be conducted as a single research effort and data from each participating Principal Investigator will be included in the analysis of results from the investigator at the Lead Organization.
- The Principal Investigator at the Lead Organization is responsible for assuring that IRB approval has been obtained at each Participating Organization prior to participant enrollment.
- The investigator at the Lead Organization will be responsible for the conduct of the study, will monitor study progress (including review of clinical data from each Participating Organization), and will have ultimate responsibility for all reporting of the trial to DCP.
- Particular attention should be paid to describing the procedures for monitoring the progress of multi-institution trials, including: reporting adverse drug reactions, the frequency by which the required records will be sent to the investigator at the Lead Organization, the methods by which accuracy of the data submitted is verified, and the composition and functioning of a data and safety monitoring committee.
- The Lead Organization is responsible for monitoring the Participating Organizations for each protocol.
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How to Submit a Protocol and Protocol-Related Documents
All document submissions must be sent electronically to the PIO. Submissions sent elsewhere will not be accepted for review. Incomplete submissions will be returned to the Principal Investigator.
- A cover letter that addresses comments in the Letter of Intent (LOI) review.
- DCP Consortia Protocol Submission Worksheet (pdf, 35kb) (doc, 130kb)
- Submit a complete protocol using the DCP Chemoprevention Protocol Template. (doc, 320kb) - A complete protocol submission includes the protocol document, consent form, CRF, and all appendices. Questionnaires or other data collection tools should also be included in the submission.
- Ensure that the documents include a document version and date, the table of content numbering matches section numbers and page numbers, and that all pages are numbered.
- An informed consent document using the National Cancer Institute (NCI) Recommendations on Informed Consent Recommendations and the DCP Chemoprevention Informed Consent Template (pdf, 54kb) (doc, 110kb).
- An electronic acknowledgement of the protocol receipt is sent to the PI by the DCP PIO. The DCP protocol number assigned at that point must be referenced in all subsequent communications with DCP about the study.
- PIO will send the investigator an e-mail indicating that the protocol is complete and accepted for review or that the protocol is incomplete and is returned to the investigator for modifications.
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Review and Approval
- The DCP Protocol and Safety Review Committee will review the protocol within 4 weeks of receipt.
- A cover letter and consensus review document will be e-mailed to the PI following the Protocol and Safety Review Committee (PSRC).
- Further revisions may be recommended or required prior to DCP protocol approval.
- The investigator should follow the directions in the cover letter to resubmit the protocol documents within the timeframe defined in the letter.
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