DoD Kidney Cancer, Clinical Trial Award

The KCRP Clinical Trial Award supports the rapid implementation of early-phase 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, surgical procedures, behavior modifications, 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 placebo or other 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.army.mil/pubs/pdf/ Human%20Subjects%20Resource%20Document.pdf. Principal Investigators (PIs) seeking funding for a preclinical research project should consider one of the other FY22 KCRP program announcements being offered.

Cell Therapy Focus Option (New for FY22): The FY22 KCRP Clinical Trial Award may support cell therapy clinical trials. Such studies may require additional resources due to required optimization of cell therapy manufacturing or clinical trial correlative studies. Applicants may request higher levels of funding within the defined period of performance. The application must demonstrate access to the necessary specimens and/or data of the proposed cohort. Appropriate access must be confirmed at the time of application submission.

Qualified Collaboration Option (New for FY22): The KCRP will offer a Qualified Collaboration Option to encourage leveraging of existing infrastructure previously funded. 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.

Key aspects of the KCRP Clinical Trial Award mechanism:

• 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 U.S. Food and Drug Administration (FDA)-regulated studies.

• 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. The quality and stability of the product should be documented and commensurate with current FDA manufacturing standards applicable to the type and phase of product being developed (i.e., Quality System Regulation, Good Manufacturing Practice [GMP] guidelines). Funds from this award may not be used to support costs associated with producing or acquiring the specified intervention (i.e., purchasing from the manufacturer).

• 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 and use of an appropriate database to safeguard and maintain the integrity of the data. If FDA-regulated, the trial must use a 21 CFR 11-compliant database and appropriate data standards. For more on data standards, see https://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/ FormsSubmissionRequirements/ElectronicSubmissions/UCM511237.pdf.

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/developmentapprovalprocess/howdrugsaredevelopedandapproved/approvalapplications/investigationalnewdrugindapplication/default.htm.

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.

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 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 FY22 KCRP Clinical Trial Award or an FY22 KCRP Clinical Trial Award – Qualified Collaboration Option will not exceed $1.5M. The anticipated direct costs budgeted for the entire period of performance for an FY22 KCRP Clinical Trial Award – Cell Therapy Focus Option will not exceed $2.0M. Refer to Section II.D.5, Funding Restrictions, for detailed funding information.

Awards will be made no later than September 30, 2023. For additional information, refer to Section II.F.1, Federal Award Notices.

The CDMRP expects to allot approximately $8.0M to fund approximately 2 Clinical Trial Award and 1 Clinical Trial Award – Cell Therapy Focus Option applications. 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 FY22 funding opportunity will be funded with FY22 funds, which will expire for use on September 30, 2028.

Research Involving Human Anatomical Substances, Human Subjects, or Human Cadavers: All DOD-funded research involving new and ongoing research with human anatomical substances, human subjects, or human cadavers must be reviewed and approved by the USAMRDC Office of Research Protections, Human Research Protection Office (HRPO), 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 submission is not required. Allow up to 3 months to complete the HRPO regulatory review and approval process following submission of all required and complete documents to the HRPO. Refer to the General Application Instructions, Appendix 1, and the Human Research Protections Office Resources and Overview document available on the electronic Biomedical Research Application Portal (eBRAP) “Funding Opportunities & Forms” web page (https://ebrap.org/eBRAP/public/Program.htm) for additional information.

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 VA Resources: If the proposed research involves access to active-duty military 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.