DoD Kidney Cancer, Clinical Trial Award

The KCRP Clinical Trial Award supports the rapid implementation of clinical trials (phase 0, phase 1, phase 1/2) with the potential to have a significant impact on the treatment or management of kidney cancer. Clinical trials may be designed to evaluate promising new products, pharmacologic agents (drugs or biologics), devices, clinical guidance, and/or emerging approaches and technologies. Therapeutic approaches testing existing interventions for new indications in kidney cancer are also encouraged. It is anticipated that outcomes from studies funded by this award will provide scientific rationale for subsequent development of larger, efficacy-based clinical trials of interventions that will transform kidney cancer patient care.

Funding from this award mechanism must support a clinical trial. A clinical trial is defined as a research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include a placebo or another control) to evaluate the effects of the interventions on biomedical or behavioral health-related outcomes. For more information, a Human Subject Resource Document is provided at https://cdmrp.health.mil/pubs/pdf/Human%20Subjects%20Resource%20Document.pdf. Principal Investigators (PIs) seeking funding for a preclinical research project should consider one of the other FY23 KCRP program announcements being offered. Studies that do not seek to measure safety, effectiveness, and/or efficacy outcome(s) of an intervention are not considered clinical trials.

For the purposes of this funding opportunity, Regulatory Agency refers to the U.S. Food and Drug Administration (FDA) or any relevant international regulatory agency unless otherwise noted.

Key aspects of the KCRP Clinical Trial Award:

• Clinical Trial Start Date: The proposed clinical trial is expected to begin no later than 12 months after the award date or 18 months after the award date for studies regulated by the Regulatory Agency.

• Preliminary data are required: Inclusion of preliminary data relevant to the proposed clinical trial is required.

• Study Population: The application should demonstrate the availability of and access to a suitable patient population that will support a meaningful outcome for the study. The application should include a discussion of how accrual goals will be achieved, as well as the strategy for inclusion of women and minorities in the clinical trial appropriate to the objectives of the study.

• Intervention Availability: The application should demonstrate the documented availability of and access to the drug/compound, device, and/or other materials needed, as appropriate, for the proposed duration of the study.

• Personnel and Environment: The application should demonstrate the study team’s expertise and experience in all aspects of conducting clinical trials, including appropriate statistical analysis, knowledge of FDA processes (if applicable), and data management. The application should include a study coordinator(s) who will guide the clinical protocol through the local Institutional Review Board (IRB) of record and other federal agency regulatory approval processes, coordinate activities from all sites participating in the trial, and coordinate participant accrual. The application should show strong institutional support and, if applicable, a commitment to serve as the FDA regulatory sponsor, ensuring all sponsor responsibilities described in the Code of Federal Regulations, Title 21, Part 312 (21 CFR 312), Subpart D, are fulfilled.

• Statistical Analysis and Data Management Plans: The application should include a clearly articulated statistical analysis plan, a power analysis reflecting sample size projections that will answer the objectives of the study, and a data management plan that includes use of an appropriate database to safeguard and maintain the integrity of the data. If required by a Regulatory Agency, the trial must use a 21 CFR 11-compliant database and appropriate data standards.

If the proposed clinical trial involves the use of a drug that has not been approved by the FDA for the proposed investigational use, then an Investigational New Drug (IND) application to the FDA that meets all requirements under 21 CFR 312 may be required. It is the responsibility of the applicant to provide evidence from the IRB of record or the FDA if an IND is not required. If an IND is required, the IND application must be submitted to the FDA by the Clinical Trial Award application submission deadline. The IND should be specific for the product (i.e., the product should not represent a derivative or alternate version of the investigational agent described in the IND application) and indication to be tested in the proposed clinical trial. For more information on IND applications, the FDA has provided guidance at https://www.fda.gov/drugs/types-applications/investigational-new-drug-ind-application.

If the investigational product is a device, then an Investigational Device Exemption (IDE) application to the FDA that meets all requirements under 21 CFR 812 may be required. It is the responsibility of the applicant to provide evidence if an IDE is not required or the device qualifies for an abbreviated IDE. If an IDE is required, the IDE application must be submitted to the FDA by the Clinical Trial Award application submission deadline. The IDE should be specific for the device (i.e., should not represent a derivative or modified version of the device described in the IDE application) and indication to be tested in the proposed clinical trial.

If the clinical trial of an investigational product will be conducted at international sites, evidence that an application to the relevant national regulatory agency of the host country(ies) has been submitted by the Clinical Trial Award application submission deadline is required.

Funded trials are required to post a copy of the informed consent form used to enroll subjects on a publicly available federal website in accordance with federal requirements described in 32 CFR 219. Funded studies are required to register the study in the National Institutes of Health (NIH) clinical trials registry, www.clinicaltrials.gov, prior to initiation of the study. Refer to the General Application Instructions, Appendix 1, Section B, for further details.

Optional Qualified Collaborations: The KCRP encourages applicants to partner with Qualified Collaborators to leverage existing infrastructure previously funded by the KCRP. Qualifying organizations must be a federally funded partnership/consortium, such as the Kidney Cancer Research Consortium, with established infrastructure to support multi-institutional studies to leverage shared resources and core capabilities such as data management, clinical trial database administration, statistical analysis, tissue repositories, etc., that will improve study efficiency and reduce redundancies and duplication. A letter of collaboration from the collaborating organization demonstrating their commitment is required, outlining the services that will be shared to bring value to the government.

A congressionally mandated Metastatic Cancer Task Force was formed with the purpose of identifying ways to help accelerate clinical and translational research aimed at extending the lives of advanced state and recurrent patients. As a member of the Metastatic Cancer Task Force, CDMRP encourages applicants to review the recommendations (https://health.mil/Reference-Center/Congressional-Testimonies/2018/05/03/Metastatic-Cancer-Research) and submit research ideas to address these recommendations provided they are within the limitations of this funding opportunity and fit within the FY23 KCRP priorities.

Collaborations between researchers at military or Veteran institutions and non-military institutions are strongly encouraged. These relationships can leverage knowledge, infrastructure, and access to unique clinical populations that the partners bring to the research effort, ultimately advancing cancer research that is of significance to the Warfighter, military families, and the American public.

The types of awards made under the program announcement will be assistance agreements. An assistance agreement is appropriate when the federal government transfers a “thing of value” to a “state, local government,” or “other recipient” to carry out a public purpose of support or stimulation authorized by a law of the United States instead of acquiring property or service for the direct benefit and use of the U.S. government. An assistance agreement can take the form of a grant or cooperative agreement. The level of involvement on the part of the Department of Defense (DOD) during project performance is the key factor in determining whether to award a grant or cooperative agreement. If “no substantial involvement” on the part of the funding agency is anticipated, a grant award will be made (31 USC 6304). Conversely, if substantial involvement on the part of the funding agency is anticipated, a cooperative agreement will be made (31 USC 6305), and the award will identify the specific substantial involvement. Substantial involvement may include, but is not limited to, collaboration, participation, or intervention in the research to be performed under the award. The award type, along with the start date, will be determined during the negotiation process.

The anticipated direct costs budgeted for the entire period of performance for an FY23 KCRP Clinical Trial Award should not exceed $1.5M. Refer to Section II.D.5, Funding Restrictions, for detailed funding information. Awards will be made no later than September 30, 2024. For additional information, refer to Section II.F.1, Federal Award Notices.

The CDMRP expects to allot approximately $2.4M to fund approximately one Clinical Trial Award application. Funding of applications received is contingent upon the availability of federal funds for this program as well as the number of applications received, the quality and merit of the applications as evaluated by scientific and programmatic review, and the requirements of the government. Funds to be obligated on any award resulting from this funding opportunity will be available for use for a limited time period based on the fiscal year of the funds. It is anticipated that awards made from this FY23 funding opportunity will be funded with FY23 funds, which will expire for use on September 30, 2029. Research Involving Human Data, Human Anatomical Substances, Human Subjects, or Human Cadavers: All DOD-funded research involving new and ongoing research with human data, human anatomical substances, human subjects, or human cadavers must be reviewed and approved by the USAMRDC Office of Human and Animal Research Oversight (OHARO), Office of Human Research Oversight (OHRO), prior to research implementation. This administrative review requirement is in addition to the local IRB or Ethics Committee (EC) review. Local IRB/EC approval at the time of application submission is not required; however, local IRB/EC approval is necessary prior to OHRO review. Allow up to 3 months to complete the OHRO regulatory review and approval process following submission of all required and complete documents to the OHRO. Refer to the General Application Instructions, Appendix 1, and the OHARO web page (https://mrdc.health.mil/index.cfm/collaborate/research_protections/hrpo) for additional information.

As of January 20, 2020, U.S. institutions engaged in non-exempt cooperative research must rely on a single IRB to review and approve the portion of the research conducted at domestic sites (45 CFR 46.114(b)). If the proposed, non-exempt research involves more than one U.S.-based institution, a written plan for single IRB review arrangements must be provided at the time of application submission or award negotiation. The lead institution responsible for developing the master protocol and master consent form should be identified and should be the single point of contact for regulatory submissions and requirements.

Communication and data transfer between or among the collaborating institutions, as well as how specimens and/or imaging products obtained during the study will be handled, should be included in the appropriate sections of the application. A separate intellectual and material property plan agreed on by all participating institutions is also required for multi-institutional clinical trials.

If the proposed research involves more than one institution, plans for the multi-institutional structure governing the research protocol(s) should be outlined. In addition, a written plan for single IRB review arrangements must be provided for research conducted in the United States involving more than one institution. The lead institution responsible for developing the master protocol and master consent form should be identified and should be the single point of contact for regulatory submissions and requirements. Communication and data transfer between or among the collaborating institutions, as well as how specimens and/or imaging products obtained during the study will be handled, should be included in the appropriate sections of the application. A separate intellectual and material property plan agreed on by all participating institutions is also required for multi-institutional clinical trials.

Use of DOD or Department of Veterans Affairs (VA) Resources: If the proposed research involves access to active-duty military and/or VA patient populations and/or DOD or VA resources or databases, the application must describe the access at the time of submission and include a plan for maintaining access as needed throughout the proposed research. Refer to Section II.D.2.b.ii, Full Application Submission Components, for detailed information. Refer to the General Application Instructions, Appendix 1, for additional information.