Early Phase Investigator-Initiated Clinical Trials for Cancer-Targeted Diagnostic and Therapeutic Interventions is a grant from the National Cancer Institute (NCI) at NIH that funds Phase 0, I, and II investigator-initiated clinical trials focused on cancer-targeted diagnostics and therapeutics.

This R01 funding opportunity supports early phase trials that test novel diagnostic and treatment approaches in cancer patients, aiming to accelerate the development of effective interventions. Eligible applicants include research institutions, universities, and other organizations capable of conducting clinical trial research. The application deadline is June 5, 2026.

PAR-25-081: National Cancer Institute's Investigator-Initiated Early Phase Clinical Trials for Cancer Treatment and Diagnosis (R01 Clinical Trial Required) This funding opportunity was updated to align with agency priorities. Carefully reread the full funding opportunity and make any needed adjustments to your application prior to submission. Department of Health and Human Services Part 1.

Overview Information Participating Organization(s) National Institutes of Health ( NIH ) Components of Participating Organizations National Cancer Institute ( NCI ) Funding Opportunity Title National Cancer Institute's Investigator-Initiated Early Phase Clinical Trials for Cancer Treatment and Diagnosis (R01 Clinical Trial Required) R01 Research Project Grant Notices of Special Interest associated with this funding opportunity January 28, 2026 - NIH Removing AIDS Application Due Dates from NOFOs.

See Notice NOT-OD-26-029 . March 31, 2025 - This funding opportunity was updated to align with agency priorities. Carefully reread the full funding opportunity and make any needed adjustments to your application prior to submission.

April 4, 2024 - Overview of Grant Application and Review Changes for Due Dates on or after January 25, 2025. See Notice NOT-OD-24-084 . August 31, 2022 - Implementation Changes for Genomic Data Sharing Plans Included with Applications Due on or after January 25, 2023.

See Notice NOT-OD-22-198 . August 5, 2022 - Implementation Details for the NIH Data Management and Sharing Policy. See Notice NOT-OD-22-189 .

Funding Opportunity Number (FON) Companion Funding Opportunity See Section III. 3. Additional Information on Eligibility.

Assistance Listing Number(s) 93. 393, 93. 394, 93.

399, 93. 395 Funding Opportunity Purpose Through this Notice of Funding Opportunity (NOFO), the National Cancer Institute (NCI) is soliciting research projects that implement early phase (Phase 0, I, and II) investigator-initiated clinical trials focused on cancer-targeted diagnostic and therapeutic interventions of direct relevance to the research mission of DCTD and OHAM.

The proposed project must involve at least 1 clinical trial related to the scientific interests of one or more of the following research programs: Cancer Therapy Evaluation Program, Cancer Imaging Program, Cancer Diagnosis Program, Radiation Research Program, Complementary and Alternative Medicine Program and/or the HIV and AIDS Malignancies Research Programs.

Applicants may propose to conduct an early phase trial by itself, or in combination with another research aim(s) as appropriate. This NOFO does not accept Phase III clinical trials. Open Date (Earliest Submission Date) The following table includes NIH standard due dates marked with an asterisk.

Renewal / Resubmission / Revision (as allowed) AIDS - New/Renewal/Resubmission/Revision, as allowed All applications are due by 5:00 PM local time of applicant organization. Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

Required Application Instructions It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide , except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts ). Conformance to all requirements (both in the Application Guide and the NOFO) is required and strictly enforced.

Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

There are several options available to submit your application through Grants. gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

Use the NIH ASSIST system to prepare, submit and track your application online. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants. gov and eRA Commons to track your application.

Check with your institutional officials regarding availability. Workspace to prepare and submit your application and eRA Commons to track your application. Part 1.

Overview Information Part 2. Full Text of Announcement Section I. Notice of Funding Opportunity Description Section II.

Award Information Section III. Eligibility Information Section IV. Application and Submission Information Section V.

Application Review Information Section VI. Award Administration Information Section VII. Agency Contacts Section VIII.

Other Information Part 2. Full Text of Announcement Section I.

Notice of Funding Opportunity Description Due to the introduction of the NIH policy, set forth in " NOT-OD-16-147 ," to create a Notice of Funding Opportunity (NOFO) that is specifically designed for applications that involve clinical trials, the National Cancer Institute (NCI) has established two program announcements for R01 applications to support investigator-initiated clinical trials that are now reissued as: 1.

PAR-25-081 (this NOFO), which seeks applications for support of early phase (Phase 0, I, and II) medical imaging and oncologic interventional clinical trials relevant to the mission of the NCI's Division of Cancer Treatment and Diagnosis ( DCTD ); and Office of HIV and AIDS Malignancies ( OHAM ); and 2.

PAR-25-167 (companion NOFO), which seeks applications for support of cancer prevention and control clinical trials relevant to the missions of NCI's Division of Cancer Prevention ( DCP ) and NCI's Division of Cancer Control and Population Sciences ( DCCPS ), respectively.

Applicants should be aware of the types of scientific programs that each named NCI Division manages to determine the appropriate NOFO defined above for submission of applications. In addition, NCI does not participate in the NIH-wide Research Project Grant (Parent R01 Clinical Trial Required) funding opportunity.

However, applicants who want to request R01 support for clinical and translational cancer research projects that do not involve clinical trials can submit their application to the " NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)" NOFO.

Through this NOFO, the NCI intends to support research projects that include and implement early phase (Phase 0, I, and II) investigator-initiated clinical trials on cancer-targeted diagnostic and therapeutic interventions of direct relevance to the research mission of the NCI's DCTD and OHAM . All applications submitted to this NOFO should address the mission and priorities of one or more of the following programs: 1.

the Cancer Therapy Evaluation Program (CTEP, DCTD); 2. the Cancer Imaging Program (CIP, DCTD); 3. the Cancer Diagnosis Program (CDP, DCTD); 4.

the Radiation Research Program (RRP, DCTD); 5. the Office of Complementary and Alternative Medicine (OCCAM, DCTD); and 6. the Office of HIV and AIDS Malignancies (OHAM, Office of the Director).

Applicants can learn more about the various program goals, research priorities, and strategies developed to diagnose and treat cancer by visiting the DCTD website and the OHAM website. Applications submitted to this NOFO must meet the NIH definition of a clinical trial (see NOT-OD-15-015 ) and provide specific clinical trial information as described in this NOFO and the NIH application FORMS-H guidelines (See: https://grants. nih.

gov/grants/guide/notice-files/NOT-OD-21-169. html.) Note: To help determine if your study meets the NIH definition of a clinical trial, review the case studies, the frequently asked questions, and answer the questions listed on the NIH Grants & Funding website at https://grants.

nih. gov/ct-decision/index. htm .

Investigators who are involved in clinical trials supported through this NOFO are expected to follow the NIH Policy on Good Clinical Practice (see NOT-OD-16-148 ). Investigators who are new to the conduct of clinical trials are welcome to apply to this NOFO and participate in clinical trial research, but they are encouraged to identify appropriate mentors and to establish the right personnel compositions for the clinical trial teams.

This NOFO is applicable to a broad range of clinical trial evaluations designed to improve the diagnosis and treatment of cancer in areas of common and unmet need. Each application should represent the applicant's or applicants' interest(s) and competencies, as well as the science related to diagnosis and treatment of cancer patients through well-designed and executed clinical trials.

In addition, strategies to assess feasibility can include a novel area of investigation, new experimental systems, and/or existing technologies in a new area. Although the rationale must be supported by preliminary data, the proposed clinical investigations may include study designs, methods, and interventions that are not themselves innovative but address important questions and/or unmet needs.

General Areas of Research This NOFO is applicable to a broad range of clinical trial evaluations that improve the diagnosis and treatment of cancer in areas of common and unmet need.

Potential areas of research may include, but are not limited to, the clinical evaluation of new or improved anticancer drugs and biologics, including immunotherapies, new or improved imaging technologies and surgical interventions, novel approaches to radiation therapy, and incorporation of complementary and alternative medicine approaches to treatment.

The research component may include the development of therapeutics, diagnostics, and devices in combination with standard care therapies including chemotherapy, immunotherapy, surgery, radiotherapy, or any combination of these modalities. Additional research aims can be proposed as part of the overall research plan provided it includes at least 1 clinical trial to be completed within the project period.

Examples of projects appropriate to this NOFO include applications with the primary intent of conducting early phase clinical trial(s) for testing the efficacy, safety, clinical management, and/or implementation of novel therapeutic or diagnostic interventions, such as drugs, biologics, vaccines, stem cells, medicinal natural products, clinical laboratory tests, imaging agents, imaging devices, or image-guided therapies.

Applicants may, for example, propose to conduct an early phase clinical trial that: Evaluates the dosing, safety, tolerability, pharmacokinetics, pharmacodynamics, and effectiveness of novel anticancer drugs, biologics, immunotherapeutics (e.g., adoptive cell transfer therapies), and their combinations as well as imaging agents or other interventions; Tests approved agents and combinations for new indications; Evaluates new or improved image-guided interventions, radiation modalities, means of delivery, or combinations with novel agents; Tests imaging probes or quantitative approaches incorporated into commercially available imaging instrumentation (e.g., positron emission tomography [PET], single photon-emission computed tomography [SPECT], magnetic resonance [MR] imaging, computed tomography [CT], ultrasound [US], optical imaging, and photoacoustic imaging [PAI]); Assesses tools, methods, devices, and instruments that can perform at the molecular, cellular, and organ levels; Investigates multi-parametric imaging approaches and biomarker detection assays including radiomics, radiogenomics, genomics, proteomics, and metabolomics; Evaluates imaging or laboratory biomarker activity, pharmacodynamic response, target engagement, dose-response trends; Selects or ranks the best potential interventions, technologies, and/or dosing regimens to be evaluated in a subsequent trial, based on tolerability, safety data, biological activity, or preliminary clinical efficacy (e.g., a futility trial); Conducts exploratory investigational new drug (IND) and/or investigational device exemption (IDE) studies (visit the FDA's website to obtain guidance documents on INDs , IDE s, and Clinical Trials ; and Evaluates integrative medicine approaches such as diets, nutrients, herbs, bioactive food components, pre/probiotics, microbiota practices, and mind-body interventions (e.g., acupuncture, exercise, meditation, and sleep) to improve standard of care or investigational therapeutics.

Research approaches should focus on interventions with outcome measures that contribute to the improvement of knowledge regarding mechanism of action or resistance, therapeutic index, prediction of response, standard-of-care practices, and/or quality of life. Research that combines expertise in more than one clinical research area (e.g., the development of therapeutics, diagnostics, and devices) is also welcome.

Prior to submitting applications to this NOFO, applicants are encouraged to review the NIH clinical trial case studies and frequently asked questions to determine if their clinical study meets the NIH definition of a clinical trial. Applicants should also consult with the Scientific/Research contacts for the area of science for which they are planning to develop an application.

Early contact (at least 12 weeks prior to submission) is encouraged. This period provides an opportunity for the NCI staff to discuss the scope and goals, and to provide information and guidance to the applicants.

Type of Clinical trials to be supported by this NOFO Clinical trials proposed must meet the NIH definition of a clinical trial (see NOT-OD-15-015 ) and should contribute to the advancement of evidence-based medicine/practice and the sciences that support it. Applicants may propose to conduct an early phase trial by itself, or in combination with other non-clinical trial research aims as appropriate.

The NOFO will support the conduct of investigator-initiated oncologic intervention research at all early stages, from early mechanistic research and intervention development (e.g., Phase 0 and/or I) through implementation and cost-effectiveness research.

NCI funds may be used to support single-site, multi-site, hypothesis-driven, pathway-related, exploratory/feasibility and pragmatic trials (as defined below) designed to improve the management of care for patients with cancer. The trial design should be appropriate for the hypothesis to be tested. This NOFO also supports randomized Phase II trials that can be performed within the temporal and fiscal limits of this program announcement.

In addition, applicants may find the NIH-FDA Clinical Trial e-Protocol Writing Tool and Templates helpful in preparing Phase II clinical trial protocols conducted under an FDA Investigational New Drug (IND) or Investigational Device Exemption (IDE) Application. These web-based resources, which is optional for use here, can be found at https://grants. nih.

gov/policy/clinical-trials/protocol-template. htm . Note that Phase III clinical trials will not be accepted through this NOFO.

Description of the type of clinical trials that can be supported include: Single-site clinical trial(s): Early phase trials where the protocol is implemented by one investigational site that conducts and coordinates the protocol.

While a single-site clinical trial may enroll participants from multiple locations/clinics within a geographic area, those participants will receive an intervention or undergo outcome assessments under the direction and oversight of one research team at one investigational site. Multi-site clinical trial(s): Early phase trials that recruit study subjects from two or more geographically distinct enrollment sites, or centers.

The sites are usually distinct in other characteristics (e.g., demographic, socioeconomic, or clinical). Study protocols are followed at these sites. Mechanistic clinical trial(s): Hypothesis-driven interventional studies (i.e., early phase trials) focused on basic and/or translational, discovery research on the biology and pathophysiology of cancer or the mechanism of action of an intervention.

Feasibility clinical trial(s): Early phase trials that propose to break new ground and/or extend previous discoveries toward new directions and/or applications. Pragmatic trial(s): Early phase trials that test an intervention under the usual clinical conditions in which it will be applied, while explanatory trials do so under more idealized circumstances.

Ancillary clinical trial(s): Early phase trials that address research questions related to ongoing trials but are distinct from the primary/secondary objectives of the parent study. An ancillary clinical trial is an independent trial that includes an additional intervention prospectively assigned to patients or a subpopulation of patients within a larger trial. For helpful examples, see case studies 42b and 42c .

Pharmacodynamic trial(s): Early phase trials that link outcomes to measurements on pre- and post-treatment specimens to test hypotheses about therapeutic mechanisms based on pre-clinical data. Biomarker-driven trial(s): Early phase trials that test predictive or prognostic biomarker findings obtained from pilot trials.

Co-clinical trial(s): Early phase trials that involve patients and in parallel (or sequentially) animal or human-in-animal models of cancer that mirror the genetics and biology of the patients’ malignancies or pre-cancerous lesions. The co-clinical trial should include either a therapeutic goal (e.g., the prediction, staging, and/or measurement of tumor response to therapies) or an early diagnostic goal.

HIV and AIDS related trials : Any of the above listed trial types conducted in individuals with an underlying human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS). Applications Not Responsive to this NOFO Applications proposing these kinds of studies will not be considered responsive. Applications not responsive to this NOFO will not be reviewed.

Investigator-initiated phase III cancer-related medical/oncologic intervention and/or investigational imaging clinical trials as specified in the NCI policy for R01 and P01 activity codes found in Notice NOT-CA-13-012 .

Applications involving only animal and/or in vitro studies that do not complement a trial are not appropriate; however, applications proposing both animal work and/or in vitro studies and a clinical trial are appropriate. Applications proposing only observational studies that do not meet the NIH definition of a clinical trial.

These applications may be submitted as R01s to the NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed). Clinical trials to investigate behavioral interventions without a therapeutic endpoint are not supported under this announcement but could be submitted to the NCI investigator-initiated clinical trials NOFO sponsored by DCP and DCCPS .

Planned or ongoing clinical trials performed by NCI-funded networks and special programs (e.g., National Clinical Trials Network [NCTN], Experimental Therapeutics Clinical Trials Network [ETCTN], and Specialized Programs of Research Excellence [SPOREs]. Clinical trial applications requesting to utilize the NCTN and/or ETCTN infrastructure and/or resources that do not have NCI prior approval.

These programs operate under a cooperative agreement in which NCI has the responsibility for final review and approval of all protocols and subsequent amendments as well as the use of biospecimens collected in association with the Network trials.

Applicants must consult the appropriate Principal Investigator of the NCTN Group or the ETCTN Lead Academic Organization to determine if NCI approval has been obtained for a potential submission. See Section VIII. Other Information for award authorities and regulations.

Investigators proposing NIH-defined clinical trials may refer to the Research Methods Resources website for information about developing statistical methods and study designs. Section II. Award Information Grant: A financial assistance mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.

Application Types Allowed The OER Glossary and the How to Apply Application Guide provide details on these application types. Only those application types listed here are allowed for this NOFO. Required: Only accepting applications that propose clinical trial(s).

Need help determining whether you are doing a clinical trial? Funds Available and Anticipated Number of Awards The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications. Application budgets are limited to no more than $499,999 in direct costs per year.

The maximum project period is 5 years. NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this NOFO. Section III.

Eligibility Information Higher Education Institutions Public/State Controlled Institutions of Higher Education Private Institutions of Higher Education Nonprofits Other Than Institutions of Higher Education Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education) Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education) For-Profit Organizations (Other than Small Businesses) City or Township Governments Special District Governments Indian/Native American Tribal Governments (Federally Recognized) Indian/Native American Tribal Governments (Other than Federally Recognized).

Eligible Agencies of the Federal Government U.S. Territory or Possession Independent School Districts Public Housing Authorities/Indian Housing Authorities Native American Tribal Organizations (other than Federally recognized tribal governments) Faith-based or Community-based Organizations Non-domestic (non-U.S.) Entities (Foreign Organizations) Non-domestic (non-U.S.) Entities (Foreign Organizations) are eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply. Foreign components, as defined in the NIH Grants Policy Statement , are allowed. Applicant organizations must complete and maintain the following registrations as described in the How to Apply- Application Guide to be eligible to apply for or receive an award.

All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference the NIH Grants Policy Statement Section 2.

3. 9. 2 Electronically Submitted Applications for additional information.

System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually . The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.

NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM. Unique Entity Identifier (UEI) - A UEI is issued as part of the SAM. gov registration process.

The same UEI must be used for all registrations, as well as on the grant application. eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants. gov registrations; all registrations must be in place by time of submission.

eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application. Grants. gov – Applicants must have an active SAM registration in order to complete the Grants.

gov registration. Program Directors/Principal Investigators (PD(s)/PI(s)) All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons.

If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Eligible Individuals (Program Director/Principal Investigator) Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with their organization to develop an application for support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the How to Apply-Application Guide. This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement Section 1. 2 Definition of Terms .

3. Additional Information on Eligibility Applicant organizations may submit more than one application, provided that each application is scientifically distinct. The NIH will not accept duplicate or highly overlapping applications under review at the same time, per NIH Grants Policy Statement Section 2.

3. 7. 4 Submission of Resubmission Application .

This means that the NIH will not accept: A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application. A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.

An application that has substantial overlap with another application pending appeal of initial peer review (see NIH Grants Policy Statement 2. 3. 9.

4 Similar, Essentially Identical, or Identical Applications ). Section IV. Application and Submission Information 1.

Requesting an Application Package The application forms package specific to this opportunity must be accessed through ASSIST, Grants. gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.

gov Workspace are available in Part 1 of this NOFO. See your administrative office for instructions if you plan to use an institutional system-to-system solution. 2.

Content and Form of Application Submission It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide except where instructed in this notice of funding opportunity to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced.

Applications that are out of compliance with these instructions may be delayed or not accepted for review. All page limitations described in the How to Apply- Application Guide and the Table of Page Limits must be followed. Instructions for Application Submission The following section supplements the instructions found in the How to Apply- Application Guide and should be used for preparing an application to this NOFO.

All instructions in the How to Apply - Application Guide must be followed. SF424(R&R) Project/Performance Site Locations All instructions in the How to Apply- Application Guide must be followed. SF424(R&R) Other Project Information All instructions in the How to Apply- Application Guide must be followed.

SF424(R&R) Senior/Key Person Profile All instructions in the How to Apply- Application Guide must be followed. All instructions in the How to Apply- Application Guide must be followed. All instructions in the How to Apply-Application Guide must be followed.

PHS 398 Cover Page Supplement All instructions in the How to Apply- Application Guide must be followed. All instructions in the How to Apply- Application Guide must be followed, with the following additional instructions: Resource Sharing Plan : Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply- Application Guide.

All instructions in the How to Apply-Application Guide must be followed, with the following additional instructions: All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan.

All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan. Appendix: Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the How to Apply- Application Guide.

No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix. The following modifications apply: For applications that have the complete Clinical Trial Protocol available, combine all clinical documents in a single PDF file in the Appendix.

Resubmission applications that have modified the clinical trial(s) should indicate the changes in the Clinical Trial Protocol and update the Research Strategy section accordingly.

PHS Human Subjects and Clinical Trials Information When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the How to Apply- Application Guide, with the following additional instructions: If you answered “Yes” to the question “Are Human Subjects Involved?

” on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record. Study Record: PHS Human Subjects and Clinical Trials Information All instructions in the How to Apply- Application Guide must be followed.

Note : If the proposed project consists of an ancillary clinical trial, please complete the study record with details of the ancillary study and not the parent trial/protocol. Section 2 - Study Population Characteristics Section 2. 5 Recruitment and Retention Plan Please include a discussion of the availability of potential participants for the proposed study and anticipated yield from recruitment and screening efforts.

If there is more than one site, please provide a table showing the expected number and demographics of the population to be recruited at each site and overall. The plan should also include a discussion of experiences in recruiting and retaining similar populations, expected challenges to recruitment and retention, decision points for terminating the trial, and possible contingency plans. Section 2.

7 Study Timeline The study timeline must describe key milestones throughout the project and trial that need to be met to achieve the goals of the study. A milestone is defined as a scheduled event in the project timeline that signifies the completion of a project stage or activity. Applicants are required to provide detailed project performance and timeline objectives as outlined below.

Investigators must indicate where within the Plan the clinical trial or trials are scheduled and when the required documents will be available if not included at the time of submission. Program staff will review the milestones and timelines which can be negotiated, as needed, at the time of the award.

This section must include an estimated timeline for the following general milestones, as applicable: Status of the FDA-regulated product requiring IND or IDE if applicable. Completion of the finalized Clinical Trial Protocol for submission to NCI; Registration of clinical trial in ClinicalTrials.

gov ; Completion of regulatory approvals; Enrollment of the first subject; Enrollment of 25%, 50%, 75%, and 100% of the projected recruitment for all study participants including women, minorities, and individuals across the lifespan (as appropriate); Completion of data collection time period; Completion of primary endpoint and secondary endpoint data analyses; Completion of final report of the primary outcome; Reporting of results in ClinicalTrials.

gov ; Additionally, applicants should consider the following expectations when scheduling the above milestones: NCI expects a protocol that meets the definition of a delayed start trial to have received full IRB approval with all regulatory requirements met (as appropriate) within the first year of the project period.

Furthermore, NCI expects investigators proposing a delayed onset trial to have substantially engaged appropriate stakeholders and have all clinical trial planning activities completed within the first 3 years of the project. Applicants should also give contingency plans if they do not meet the milestones and address any other implementation activities necessary such as start-up tasks to achieve trial completion.

Section 3 - Protection and Monitoring Plans Section 3. 3 Data and Safety Monitoring Plan In addition to the description of safety monitoring, address plans to monitor trial performance, including plans to assure fidelity to the protocol and integrity of the data. Information about Data and Safety Monitoring Plans are available at https://humansubjects.

nih. gov/data_safety . Section 4 - Protocol Synopsis 4.

1. a. Detailed Description A detailed description of the protocol is required in this section regardless of the clinical trial protocol attachment in the Appendix.

It should summarize the necessary elements of the trial and supplement the Research Strategy, which is meant to justify the need, its potential impact, and provide supporting preclinical and/or clinical evidence. Applications submitted without the Clinical Protocol Synopsis are considered incomplete and will not be reviewed. Section 4.

3 Statistical Design and Power The sample size and statistical power calculations should contain enough detail, including sufficient information on the assumptions made, so that a reviewer can readily duplicate the projected sample size. The power analysis should include a discussion of the anticipated level of adherence to the intervention and rates of follow-up (i.e., drop out/lost to follow-up) during key outcome collection contacts.

A discussion of how missing data will be handled should be included. Any planned interim analysis should also be described. Section 5 - Other Clinical Trial-Related Attachments Applicants should provide a list of clinical trials that demonstrate their experience in trial coordination over the last 5 years, without duplicating information in biosketches.

A table should be provided as an attachment using the filename