DoD Kidney Cancer, Clinical Consortium Award

The Clinical Consortium Award mechanism provides support to develop and enhance collaborations and resources necessary for a network of organizations to rapidly execute phase 2 or phase 2-linked phase 1 (phase 1/2) kidney cancer clinical trials. These trials will include investigations of high-impact, novel therapeutic agents or approaches for the management or treatment of kidney cancer. Applicants are expected to demonstrate a broad understanding of kidney cancer research, including knowledge of the current state of clinical studies and priorities related to kidney cancer, and are encouraged to familiarize themselves with the FY23 KCRP’s Overarching Strategic Goals and Focus Areas and to consider this material when preparing their application. Support from this award is to be directed toward Consortium infrastructure needs rather than direct support of the trials themselves.

The principal goal of the KCRP Clinical Consortium Award is to combine the efforts of leading investigators to bring to market high-impact, novel, therapeutic strategies and interventions to improve patient outcomes and significantly decrease the impact of the disease. To facilitate global investigations, U.S. and international institutions are encouraged to apply. Submissions from institutions with access to patients from high-risk, underserved, and/or military populations (as described in the FY23 KCRP Overarching Strategic Goals and Focus Areas) are especially encouraged.

The FY23 Clinical Consortium Award mechanism will be used to select and fund six Clinical Research Sites and one Coordinating Center. PIs will be required to indicate whether the institution is applying as either the Coordinating Center with a Clinical Research Site or as a Clinical Research Site only. Institutions applying as the Coordinating Center, if not selected for funding, have the option to still be considered as a Clinical Research Site only. The Coordinating Center and Clinical Research Sites will be jointly responsible for proposing, selecting, and conducting phase 2 and phase 1/2 clinical trials focused on kidney cancer therapeutic interventions. The Coordinating Center and Clinical Research Sites funded by the FY23 KCRP Clinical Consortium Award will work with additional Clinical Research Sites that may be funded by the KCRP in future fiscal years. Additional details regarding the structure of the Consortium are described below.

The Coordinating Center, in addition to functioning as a Clinical Research Site, will serve as the Consortium information and planning nexus providing administrative, operational, and data management support services to participating Clinical Research Sites to implement Consortium clinical trials in a timely manner. Responsibilities of the Coordinating Center will include coordinating the clinical trial selection process, protocol coordination, regulatory coordination, study management and monitoring, data collection and management, statistical support, and intellectual/material property coordination. The Coordinating Center will also be responsible for launching two clinical trials, with funding already secured, to be initiated by the Consortium within the first 6 months of the performance period. In addition, the Coordinating Center will coordinate and promote best practices for human subject recruitment and will aid Clinical Research Sites in directing potential subjects to the most appropriate trials. All Sites (Clinical Research Sites and the Coordinating Center) will be required to participate in at least one of these two initial clinical trials.

Collectively, the Coordinating Center Principal Investigator (PI), the PI from each Clinical Research Site, and consumer advocates will constitute the Clinical Consortium Steering Committee. The consumer advocates must be kidney cancer patients or caregiver for someone with kidney cancer and possess a high-level familiarity with current issues in kidney cancer research. The consumer advocatesf role in the committee should be independent of their employment with a participating institution. During the Consortiumfs period of performance, the Coordinating Center PI will chair the Steering Committee. The Clinical Consortium Steering Committee will collaboratively develop and maintain a procedure for the selection of clinical trials to be implemented within the Consortium. The KCRP Grants Officer Representative must be invited to meetings of the Clinical Consortium Steering Committee as well as any other formal meetings of the Consortium.

All Sites will be responsible for working collaboratively to identify new clinical trials for implementation. Any site may serve as an entry point for clinical trials that originate from outside the Consortium. The Coordinating Center will be responsible for facilitating this entire process. The Consortium should leverage other Department of Defense (DOD) investment opportunities whenever possible (e.g., to support clinical research and correlative studies, PIs are strongly encouraged to apply for clinical trial and/or translational awards offered by the DOD).

Key requirements of the Clinical Consortium Award include:

. Responsibilities of the Consortium Participants: Procedures for the Consortium, while proposed by the Coordinating Center, will be fully developed and agreed upon by all participants working collaboratively. All references to clinical trials in the outlined responsibilities are specific to phase 2 or phase 1/2 trials; phase 3 or higher clinical trials are not included. At the discretion and expense of the government, a pre-award planning meeting may be required.

› Coordinating Center: Responsibilities specific to the Coordinating Center include:

. Adherence to the responsibilities delineated below for a Clinical Research Site

. Coordination and facilitation of at least eight clinical trials at any given time after the first 12 months of the performance period

. Development and maintenance of the Consortium organizational structure

. Provision of at least two initial clinical trial protocols for implementation by the Consortium within the first 6 months of the performance period

. Management of Consortium-developed procedures for review, selection, and implementation of clinical trials proposed by or through Consortium members ¡V Establishment and management of procedures to ensure compliance with the local Institutional Review Boards (IRBs) of all sites for the conduct of clinical trials and the protection of human subjects.

¡V Establishment and management of procedures for ensuring compliance with Food and Drug Administration (FDA) requirements for investigational agents, devices, and procedures

¡V Establishment and management of a communications plan and an ongoing communications system between the Coordinating Center and Clinical Research Sites

¡V Management of Consortium-developed quality assurance and quality control mechanisms for study monitoring, including:

„X Real-time and remote monitoring program

„X Management plan for the handling, distribution, analysis, and banking of specimens and/or imaging products generated from Consortium studies necessary for the conduct and analyses of clinical trials during the performance period of the award

„X Registration, tracking, and reporting of participant accrual

„X Timely medical review and assessment of participant data

„X Rapid reporting and communication of adverse events

„X Interim evaluation and consideration of measures of outcome

¡V Management of Consortium-developed comprehensive data collection and data management systems that address the needs of all sites in terms of access to data, data security, and data integrity measures

¡V Development of statistical plans for all Consortium clinical trials

¡V Management of Consortium-developed intellectual and material property issues among institutions participating in the Consortium

¡V Management of Consortium-developed procedures for the timely publication of major findings and other public dissemination of data

¡V Development and execution of a plan for financial sustainability leveraging collaborations, industry sponsors, and/or other funding opportunities to allow Consortium activities to continue beyond the award period of performance

¡V Presentation of written and/or oral briefings to the KCRP Programmatic Panel and USAMRDC staff at 1-day meetings typically held in the Baltimore-Washington, DC area.

Clinical Research Sites: The responsibilities of each site include:

¡V If required by the government, participation in a pre-award planning meeting with all Consortium members to discuss operational features of the Consortium, the requirements for progress and evaluation, and the award negotiations process.

¡V Full participation in the Consortium, including but not limited to, clinical trial introduction and selection, patient accrual for Consortium studies (to include accrual from high-risk, underserved, and/or military populations), data collection and timely submissions, meeting attendance, and adherence to the Consortium¡¦s operating procedures.

¡V Presentation of at least two clinical trials for the Consortium¡¦s consideration per year. For the Coordinating Center, this requirement is in addition to the initial two clinical trials required at the beginning of the award.

¡V In accordance with Consortium-developed guidelines, maintain a minimum combined accrual across all Consortium-associated studies as well as a maximum contributed percentage for each individual study.

¡V Provision for a Clinical Research Coordinator who will interact with the Clinical Research Coordinators of other Clinical Research Sites and the Supervising Clinical Research Coordinator of the Coordinating Center to expedite and guide clinical protocols through the regulatory approval processes and to coordinate patient accrual and study activities across sites.

¡V Implementation of the Consortium¡¦s core data collection methodology and strategies.

¡V Compliance with Consortium-developed quality assurance and quality control procedures, as appropriate, including:

„X Participation in a monitoring program to be managed by the Coordinating Center;

„X Implementation of the Consortium-developed management plan for acquisition, delivery, and storage of biological samples and study data; and

„X Submission of appropriate data and materials to allow for verification and review of protocol-related procedures, for example, pathology, imaging techniques, surgical methods, and therapeutic use.

¡V Implementation of procedures established by the Coordinating Center for ensuring compliance with FDA requirements for investigational agents, as appropriate.

¡V Implementation of procedures established by the Coordinating Center to meet the local IRB requirements for the conduct of clinical trials and the protection of human subjects.

Serving as a resource for the conduct of protocol-specified laboratory projects (such as tumor biology studies).

. Participation in Consortium-developed procedures for the timely publication of major findings.

. Participation in Consortium-developed procedures for resolving intellectual and material property issues among institutions participating in the Consortium.

. Submission of annual written progress reports, a final written comprehensive report, and any other reports required by the government to be outlined in the assistance agreement.

. Additional responsibilities based on recommendations and guidance from the USAMRDC staff.

. Performance Metrics: Exercise of the options for continued performance of each participant site after the first year will be contingent upon meeting performance metrics as specified in the award agreements. All references to clinical trials in the outlined responsibilities are specific to phase 2 or phase 1/2 trials; phase 3 or higher clinical trials are not included.

The Consortium Steering Committee will determine appropriate overall minimum and maximum accrual metrics for the Clinical Trial Sites per trial as part of the Consortium Standard Operating Procedures. Each Clinical Trial Site is expected to have the ability to enroll adequate numbers of evaluable individuals with kidney cancer per year into the Consortium studies OR to provide such unique expertise or facilities to otherwise justify inclusion as a site.

› Metrics for Coordinating Center Performance:

. Completion of at least four trials in the initial 12-month period of the award period of performance.

. Maintain a portfolio of at least eight open trials at any given time after the first 12 months of the period of performance.

. Successfully move agents for at least 20% of Consortium trials forward for additional testing (e.g., phase 3), which ultimately have the potential to change clinical practice. Note: The Clinical Consortium Award is not intended to support the conduct of clinical trials that test the next logical iteration of an existing treatment.

. Enrollment of at least 5% of patients from high-risk, underserved, and/or military populations (as described in the FY23 KCRP Overarching Strategic Goals and Focus Areas) in Consortium trials overall.

› Metrics for Clinical Research Site Performance:

. Enrollment of the adequate number of individuals with kidney cancer per trial each year as determined by the Consortium Steering Committee. Each Clinical Research Site is expected to participate in a minimum of eight trials initiated within Consortium over 4 years.

. Presentation of at least two trials per year or eight trials over 4 years to the Consortium for consideration.

. Accrual of at least 5% of patients from high-risk, underserved, and/or military populations (as described in the FY23 KCRP Overarching Strategic Goals and Focus Areas).

. Timely submission of quality data as outlined by the Coordinating Center.

. Plan for Financial Sustainability: It is expected that the collaborations and infrastructure developed under the Clinical Consortium Award will continue past the period of performance on this award. Coordinating Center applications must include a plan for financial sustainability that leverages collaborations, industry sponsors, and/or other funding opportunities to allow Consortium activities to continue beyond the award period of performance.

. Past Performance (if applicable): Applications from institutions that have previously received a KCRP Clinical Consortium Award must include a description of the past performance of the award, including compliance with the metrics of the previous award as well as other individual contributions made to Consortium activities. If past performance was directly affected by the COVID-19 pandemic, and/or other significant event (e.g., natural disaster), describe its impact on performance metrics and how those issues would be resolved or mitigated to increase performance for the new award.

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, the 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.

The types of awards made under the program announcement will be assistance agreements. An assistance agreement is appropriate when the federal government transfers a gthing of valueh to a gstate, local government,h or gother recipienth 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 gno substantial involvementh 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.