RFA-CA-19-031: Cancer Prevention Clinical Trials Network (CP-CTNet): CP-CTNet Sites (UG1 Clinical Trial Required)

Slots:                                                     1

Internal Deadline:                           Contact OOR if interested: first-come, first-served.

LOI:                                                        30 days prior.

External Deadline:                          August 29, 2019, 5pm PT

Award Information:                        Type: Cooperative Agreement

Estimated Number of Awards: 2

Anticipated Amount: $625,000 in direct costs for year and 1 and $1,250,000 for subsequent years of the 5-year project period.

Budgetary Requirements/Cost Sharing: All applicants should request a 5-year project period. 

Submission Process:                     PIs must submit their application as a Limited Submission through the Office of Research Application Portal: https://app.wizehive.com/webform/USCgrants

Materials to submit:

• Single Page Proposal Summary (0.5” margins; single-spaced; font type: Arial, Helvetica, or Georgia typeface; font size: 11 pt). Page limit includes references and illustrations. Pages that exceed the 1-page limit will be excluded from review.
• CV – (5 pages maximum)

Link to Award:                                  https://grants.nih.gov/grants/guide/rfa-files/RFA-CA-19-031.html

Who May Serve as PI:                   

All individuals designated as PDs/PIs for the CP-CTNet Sites must have their primary affiliation at the application-submitting institution (i.e., the LAO).

These individuals are expected to be nationally and internationally recognized leaders in clinical trials of cancer preventive agents. This expertise should reflect mainly clinical trials of preventive agents (e.g., drugs, small molecules, vaccines/biologics) using measures of drug action and efficacy that include modulation of cancer-related biomarkers.

Additional expertise in other cancer preventive approaches (including medical devices, cancer preventive surgery, risk-reducing surgery, and non-surgical ablative techniques) is also desirable.

The PDs/PIs of applications submitted in response to this FOA must not be named as Senior/Key Personnel or Other Significant Contributors on the CP-CTNet DMACC award supported under RFA-CA-18-030.

Purpose:

The purpose of the National Cancer Institute (NCI)-supported Cancer Prevention Clinical Trials Network (CP-CTNet) is to perform early phase clinical trials to evaluate the biologic effects of preventive agents and interventions and to determine clinically-relevant correlates in order to advance their development for cancer prevention. CP-CTNet Sites’ role will be to design, perform and report the results of early phase (phase 0-II) cancer prevention clinical trials.  Each CP-CTNet Site will consist of a Lead Academic Organization (LAO) and Affiliated Organizations (AOs) that will work together to perform clinical trials.  Each CP-CTNet LAO will serve as the research hub for its group and will be the UG1 applicant institution. Each LAO will constitute a multi-institutional clinical trial group and provide the infrastructure to develop, implement, and analyze the studies. The Clinical trials will be performed either by the LAO and/or AOs within each CP-CTNet site or across the CP-CTNet sites (network-wide trials).

The overall goal of CP-CTNet is to perform early phase cancer prevention clinical trials to identify agents and interventions that can advance through the various phases of clinical development. Specific objectives are summarized below:

• To efficiently design and conduct early phase clinical trials to assess the cancer preventive potential of a variety of different agents or strategies. Emphasis is on novel agents and interventions that target relevant pathways important in carcinogenesis.
• To characterize the effects of these agents and interventions on their molecular targets, as well as on other biological events associated with cancer development (such as cell proliferation, apoptosis, growth factor expression, oncogene expression, immune response) and correlate these effects with clinical endpoints.
• To develop further scientific insights into the mechanism of cancer prevention by the agent or strategy examined and to continue to develop novel potential markers as determinants of response.

Goals and Scope of Activities for CP-CTNet Sites

The main role of CP-CTNet Sites will be to design and conduct early phase (phase 0-II) cancer prevention clinical trials. For this role, each CP-CTNet LAO will be expected to serve as the main research infrastructure to support the performance of clinical trials. The LAOs will provide administrative support and oversight to clinical trial performance across their member AOs, as well as develop and perform specific clinical trials within their own institutions. The role of the AOs will be to develop clinical trials in collaboration with the LAOs and to accrue to multi-institutional studies. LAOs and AOs may participate in studies arising within their CP-CTNEt Site as well as within other CP-CTNet Sites.

The LAO will be required to interact closely with the DMACC, which will provide centralized data management, auditing, and network-wide administrative support.

Required Capabilities. Each proposed CP-CTNet Site needs to have expertise, skills, and infrastructure for the proper conduct of the following expected scope of activities:

• Designing and conducting early phase cancer prevention clinical trials using single agents or combinations of agents or other modalities. The emphasis will be on novel agents or strategies that target relevant pathways important in carcinogenesis, such as those involved in proliferation, apoptosis, differentiation, cell signaling, and others.
• Managing all aspects of study operations while adhering to all applicable rules and regulations for the conduct of clinical trials.
• Developing 1-3 new clinical trials per year, with expected accrual of 10-40 or more participants per year (10 in year 1, 40 or more starting with year 2) at each CP-CTNet Site.
• Conducting prevention clinical trials in participants at risk for cancers arising in one of at least 3 different target organs (at least one of which is breast, colon, prostate, or lung and at least one of which is not one of those 4 target organs), with access to populations at high risk for the development of cancer in these organs.
• Developing statistically appropriate clinical trial designs, including novel designs using ‘omic’ technologies, to rapidly obtain evidence of preliminary efficacy. A variety of clinical trial models, including phase 0 micro-dosing trials, phase I pharmacokinetic and pharmacodynamic (PK/PD) trials, window-of-opportunity trials performed prior to definitive treatment for premalignant lesions or cancer, and Phase IIa or IIb cancer prevention clinical trials, will be used.
• Evaluating translational endpoints in biospecimens obtained from participants in clinical trials of investigational agents (e.g., the levels of expression and/or activity of molecular targets and/or downstream effectors pertinent to a given agent).
• Assessing PK/PD of the studied agents and establishing relationships between the dose, schedule, exposure, and effect.
• Obtaining mechanistic proof-of-principle data for new agents or approaches directed at novel molecular targets important in carcinogenesis.
• Collecting, processing, and storing biospecimens from trial participants for biomarker analysis.

1. • Evaluating novel technologies (e.g., imaging, blood based, etc.) for assessing the effects of interventions

Agents to be Studied. Agents to be developed will be announced twice yearly via NCI solicitations for Letters of Intent (LOIs) for clinical trials. Agents may be developed for specific indications by individual CP-CTNet Sites or jointly by more than one Site. CP-CTNet Sites are also expected to propose unsolicited LOIs using agents or interventions available to their investigators.

Important Note: It is expected that the CP-CTNet sites supported under this FOA will have expertise in evaluating multiple types of agents, with emphasis on pharmacologic agents and immunopreventive vaccines and other immune modulators.

Required Functional Components. To realize the stated objectives, the CP-CTNet Site applicants must organize and include the following two required functional components:

1. • Clinical Trial Program – This functional component must include the scientific leadership capable of developing and conducting early phase cancer prevention clinical trials within each CP-CTNet Site or across Sites within the network and the infrastructure to oversee, support, and to ensure compliance with applicable clinical trial regulations.
   • Site Accrual Program – This functional component must provide robust accrual of study participants at the LAO and AOs to CP-CTNet trials, including accrual to studies focusing on the identified target organ sites that give rise to less common cancers (e.g., those arising in the oral cavity, esophagus, ovary, bladder, etc.), as well as timely activation of trials and provision of good clinical trial stewardship.

CP-CTNet Network Governance and Trans-Network Activities

Steering Committee: The representatives of CP-CTNet awardees (with the participation of the NCI) will be expected to form a Steering Committee as a self-governing body for the Network. For details on the composition and responsibilities of the Steering Committee, see Section VI.2 under Cooperative Agreement Terms and Conditions of the Award.

Trans-Network Research Activities

All CP-CTNet Sites will be expected to work jointly toward the CP-CTNet network goals by:

1. • Interacting with the DMACC;
   • Participating in trans-network clinical trials; and
   • Participating in high priority ancillary studies, including developmental work for new biomarkers.

Additional NCI Support for the Initiative (beyond the scope of the two CP-CTNet FOAs).

NCI/DCP will provide the following additional infrastructure support to CP-CTNet participants:

1. • Regulatory support, including Investigational New Drug (IND) application preparation and Food and Drug Administration (FDA) reporting
   • Agent acquisition, packaging, and distribution
   • Central Institutional Review Board (CIRB) review
   • Protocol receipt, review, and approval process, and study document submissions and management

NCI anticipates providing long-term storage solutions for the collected biospecimens and access to them for the research community.Visit our Institutionally Limited Submission webpage for updates and other announcements.