Part 1. Overview Information

Key Dates

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.

No late applications will be accepted for this Notice of Funding Opportunity (NOFO).

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 How to Apply - Application Guide and the NOFO) is required and strictly enforced. Applicants must read and follow all application instructions in the How to Apply - Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the How to Apply - 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.

1. Use the NIH ASSIST system to prepare, submit and track your application online.
2. 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.
3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Purpose

The purpose of this Notice of Funding Opportunity (NOFO) is to solicit applications to maintain or establish Lead Academic Organizations (LAOs) as part of the NCI Experimental Therapeutics Clinical Trials Network (ETCTN). ETCTN LAOs will design, develop, monitor, conduct, and analyze early phase clinical trials (e.g., phase 0, phase 1, phase 2, pilot, and other experimental therapeutic clinical trials) involving agents under regulatory sponsorship for New Investigational Drug (IND) applications held by NCI's Division of Cancer Treatment and Diagnosis (DCTD), Cancer Therapy Evaluation Program (CTEP). Each ETCTN LAO will participate in clinical trials it leads as well as clinical trials led by other LAOs in the network. 

The ETCTN LAOs will provide oversight for all scientific, programmatic, financial, and administrative matters related to the sites participating in ETCTN trials as part of their LAOs. ETCTN LAOs are also expected to provide mentorship for investigators who are in the early stages of their research careers with a focus on clinical trials. All ETCTN LAOs will be required to use the ETCTN Pharmacokinetic (PK) Resource Laboratory as a central resource to incorporate PK studies within their early phase clinical trials, when appropriate, to analyze pharmacokinetic endpoints, drug-drug interactions, cytochromes P450 (CYP) interactions, pharmacodynamics, and food effects associated with IND agents being evaluated in ETCTN trials. This PK Laboratory will conduct all pharmacokinetic studies for ETCTN clinical trials involving Investigational New Drug (IND) agents under the regulatory sponsorship of NCI’s Division of Cancer Treatment and Diagnosis (DCTD), Cancer Therapy Evaluation Program (CTEP).  The ETCTN Pharmacokinetic Resource Laboratory  is funded through a separate award under the NOFO listed below.

• The ETCTN – Network Pharmacokinetic Resource Laboratory under RFA-CA-27-017.

Background

Since the early 1970s, NCI's Cancer Therapy Evaluation Program (CTEP) in the Division of Cancer Treatment and Diagnosis (DCTD) has managed an early phase experimental therapeutics program that has contributed to the clinical development of anticancer agents. Through the years, NCI has formed partnerships with pharmaceutical companies, academic institutions, and individual investigators to evaluate innovative cancer therapies and in 2014, the ETCTN was created to enhance more rapid evaluation of these therapies using a coordinated, collaborative, and inclusive team-based approach to early phase experimental clinical trials and biomarker/pharmacodynamic assessment. 

The current ETCTN and its supporting infrastructure provides an established system for early-stage clinical development of novel anticancer treatments that are then evaluated in clinical trials conducted under DCTD/CTEP Investigational New Drug (IND) applications in national, high-priority areas of unmet medical need. The ETCTN also uses NCI resources to molecularly characterized tumors to identify appropriate biomarkers that can be used to select patients most likely to respond to specific agents. ETCTN clinical studies determine the safety of IND agent drug combinations, find early signals of clinical activity of these agents in targeted populations, and perform in-depth analysis of biomarkers of response and resistance. DCTD/CTEP currently holds approximately 210 INDs for investigational oncology agents/combinations which involve about 100 collaborative agreements with pharmaceutical/biotechnology companies. Agents under evaluation include, but are not limited to, small molecules, immune-oncology agents, antibodies, targeted toxins, oligonucleotides, and gene transfer agents. Through this program, hundreds of agents and agent combinations have been made available for collaborative agent development within CTEP. Effective development of these agents requires a systematic development plan for phase 1 and pilot trials, followed by phase 2 trials that, it is hoped, will conclude with definitive evaluation in phase 3 trials. The major focus of the ETCTN is on the science of clinical trial design to provide dose optimization for drug development of new cancer treatments using a team-science approach and with outreach to representative patient populations for clinical trial participation. The ETCTN's specific goals are to:

• Conduct early phase experimental therapeutic clinical trials of DCTD/CTEP-IND agents and agent combinations in high priority areas of unmet medical needs;
• Ensure efficient and timely activation and conduct of ETCTN clinical trials;
• Integrate molecular characterization, pharmacology, and cancer biology into ETCTN trials; 
• Integrate preclinical findings into trials using collection and analysis of patient biospecimens for biomarker analysis;
• Promote collaboration among ETCTN institutions and investigators across the network; and
• Provide mentorship for investigators in the early stage of their clinical research careers.

ETCTN Definitions and Organizational Framework 

Each Lead Academic Organization (LAO) receiving an award under this NOFO has a roster of clinical site(s) that enroll patients to trials conducted across the network (i.e., ETCTN LAO) that consist of one or more of the following:

• Lead Academic Organization (LAO): The institution receiving the award under this NOFO.
• Affiliated Organization (AO): A distinct legal institution partnering with the LAO to develop and lead ETCTN clinical trials and enroll patients to ETCTN trials. An AO may be included in only one ETCTN LAO UM1 application.
• Integrated Component (IC): A component of an LAO or AO that is part of the same legal entity as the LAO or AO, under the same financial management system and governance structure, but which may be at a different location.

Request for Collaborative Research Under CTEP IND Agent(s)  

The NCI Experimental Therapeutics (NEXT) Program selects agents for NCI-sponsored pre-clinical and clinical development. NCI negotiates Collaborative Research and Development Agreements (CRADAs) to develop and evaluate these agents under DCTD/CTEP IND within the ETCTN. CTEP then sets up an NCI Drug Development “Project Team” (which ETCTN LAOs are expected to participate in) to develop an initial drug development plan for the new agent(s) with an accompanying biomarker assay development plan (if warranted) that is presented to the Investigational Drug Steering Committee for evaluation. If the development plan(s) are approved, the ETCTN LAOs may then submit proposals for ETCTN clinical trials using CTEP IND agents. There are 2 pathways for submitting request letters for NCI approval:

1. In response to a “Project Team” solicitation for studies for a new agent being brought in through NEXT as part of the DCTD/CTEP IND portfolio
2. As an unsolicited request proposing an early phase trial addressing novel hypotheses using agents already in the DCTD/CTEP IND portfolio.

ETCTN LAOs are expected to encourage submission of appropriate requests with an Early Career Clinical Investigator or ECI (defined as an investigator who has completed post-oncology fellowship training within the past 10 years and who has not previously competed successfully as a Principal Investigator (PI) for a substantial independent NIH research award) as the PI for the trial. All requests with an ECI as a PI include an experienced investigator serving as mentor who provides significant direction, feedback, and oversight to the ECI. Study PIs may be affiliated with either the LAO or a participating AO; however, the LAO has complete responsibility for the trial. For details, see required Other Attachments in Section IV of this NOFO. 

Protocol Development 

Each submitted request letter is subject to review through standard procedures. If NCI and the NCI's pharmaceutical partner(s) approve a request letter, the study team works with the CTEP Central Protocol Writing Service (CPWS) to develop a protocol and consent. NCI, the pharmaceutical partners, the NCI CIRB (and other organizations as needed, including the FDA) review these documents and provide required and recommended changes that the LAO must address before CTEP will approve the protocol for activation within the ECTN. LAOs are responsible for monitoring the entire protocol development process for the trial to ensure the process meets Operational Efficiency Working Group (OEWG) timelines for early phase clinical trial development.

Trial Conduct and Leadership 

LAOs are expected to lead a broad and diverse portfolio of ETCTN trials. All ETCTN trials use the Cancer Trials Support Unit (CTSU) Oncology Patient Enrollment Network (OPEN) system to enroll patients. OPEN is integrated with an Interactive Web Response System (IWRS) for slot reservations and cohort management in ETCTN trials. Enrollment data automatically transfers to CTEP's clinical data management system (CDMS) used by the ETCTN. The NCI Clinical Trials Monitoring Service (CTMS) builds and manages the study databases for ETCTN trials from a library of standardized case report forms. DCTD/CTEP convenes a Data Monitoring Committee (DMC) or Data Safety Monitoring Board (DSMB) as needed to oversee randomized phase 2 ETCTN trials.

The study team is responsible for tracking patient enrollments and working to ensure trial accrual meets the targeted accrual rate as well as monitoring trial data in CTEP's CDMS and other systems, providing updates and responding to inquiries from DCTD/CTEP as the IND sponsor in a timely manner, and generally ensuring the trial follows the approved study design. The study team may need to amend the protocol over time for various reasons (e.g., to incorporate new safety information into the trial, respond to changes in science, make changes to enhance accrual to the trial). 

Also, although adolescents may be included in some ETCTN trials, pediatric-focused studies are not within the primary scope of the ETCTN. NCI conducts pediatric-focused early phase clinical trials through other NCI-funded mechanisms such as the Pediatric Early Phase Clinical Trials Network.

Patient specimens from ETCTN trials are tracked via the ETCTN Specimen Tracking System (STS). ETCTN trial specimens are banked centrally in the Early-Phase and Experimental Clinical Trials (EET) biospecimen bank before distribution for protocol-specified analyzes.

Although NCI DCTD/CTEP is the regulatory sponsor for all ETCTN IND trials, the ETCTN LAO is responsible for ensuring its ETCTN clinical trials and all related research complies with all applicable FDA regulations for IND studies as well as NIH, NCI, and CTEP policies. The ETCTN LAO is responsible for registering, updating, and reporting results in ClinicalTrials.gov.

Trial Participation 

ETCTN LAOs are expected to open and enroll patients to trials from across the network. To open and participate in ETCTN trials:

• Site investigators and research staff must have accounts with the CTEP Registration and Credentialing Repository (RCR) and be on the LAO roster.
• US sites must be Signatory Institutions with the NCI CIRB, which serves as the IRB of record for all US sites participating in ETCTN trials.
• Sites must complete all protocol-specific regulatory requirements, including completing and maintaining a Delegation of Tasks Log (DTL) as outlined in the Auditing Guidelines applicable to ETCTN studies.
• Sites will need to use NCI's centralized agent inventory management system, AURORA, for agent ordering and agent accountability tracking.
• ETCTN sites must have the capability to fulfill common requirements of ETCTN protocols, including acquiring fresh biopsy specimens from patients enrolled on ETCTN trials, conducting required clinical testing and advanced imaging per protocol, and utilizing an investigational pharmacy that can adequately fulfill obligations around investigational agents, including investigational radiopharmaceuticals.

In addition to LAO monitoring and oversight of their sites (AOs and/or ICs), CTEP conducts additional monitoring as well as auditing for all ETCTN trials and sites. 

Investigational Pharmacy 

It is essential that all ETCTN LAO sites (LAO, AOs, and ICs) have access to and use of a pharmacy to conduct investigational drug pharmacy operations required to adequately fulfill obligations related to investigational agents. The investigational pharmacy operations must be able to adequately fulfill obligations related to investigational agents, security, assuring proper transfer and/or final disposition of investigational agents, and adherence to local, state, and federal regulations. The investigational pharmacy must have the capability to use the AURORA system, the centralized agent inventory management system for CTEP-sponsored clinical trials using DCTD/CTEP IND agents supplied by the DCTD/CTEP Pharmaceutical Management Branch. Additionally, each institution must have access to and use of a pharmacy for the use and dispensing of investigational radiopharmaceuticals used in the conduct of clinical trials.

Biomarker Assays and Molecular Characterization 

ETCTN LAOs and its sites must also have the ability to support clinical trials by various laboratory testing of clinical biospecimens, including testing of biospecimens for integral biomarker assays in laboratories certified under CLIA Laboratory Improvement Amendments (CLIA). This also includes a requisite expertise in acquiring fresh biopsy specimens from a high percentage of patients enrolled on clinical trials, including via invasive procedures, if warranted. Interactions with Other NCI-supported Programs: In addition to NCI DCTD/CTEP staff and the ETCTN Lead Academic Organization and their participating sites, other NCI grant and contract-supported programs as well as NCI Program Advisory Committees having important supporting roles in carrying out the research objectives of the ETCTN. Thus, the PK Laboratory is required to interact, as appropriate, with such entities/programs as the DCTD Biometric Research Program (BRP); DCTD Cancer Diagnosis Program (CDP); Cancer Trials Support Unit (CTSU) with its Regulatory Support Services (RSS); NCI Central Institutional Review Board (CIRB); the ETCTN Clinical Data Management System (CDMS); the ETCTN Clinical Trials Monitoring Service (CTMS); and the NCTN Radiotherapy and Imaging Core Services Center (IROC).

Main Objectives and Requirements of this NOFO

Applicants must be able to organize and implement a comprehensive infrastructure program for the conduct of high-quality clinical trials evaluating novel anticancer agents. Thus, the proposed ETCTN LAO must be able to serve as the major resource for rapid, efficient, systematic evaluation and determination of optimal dose/schedule and safety/efficacy for specific agents and combinations of investigational agents sponsored under DCTD/CTEP INDs, as well as disease-specific treatment evaluation. To facilitate these responsibilities, the NCI DCTD/CTEP provides ETCTN awardees with standardized central operational, regulatory, and administrative support (through separate contracts beyond the scope of this NOFO, see: NCI ETCTN Program Infrastructure | Initiatives/Programs | CTEP.) 

Applicants for this NOFO for ETCTN Lead Academic Organizations (LAOs) are expected to present an overview and address the following 3 functional components:

• Overview with Organizational Structure and Management Core - The functional component is the principal component for the organizational, administrative, scientific, and operational management of the ETCTN Lead Academic Organization (LAO). This functional component provides the leadership, oversight, and coordination/integration between Clinical Trials Development & Operations Core and the Member Site Accrual and Performance Core of the LAO as well as ensuring participation by investigators within the LAO and its roster sites in "Project Teams” for new DCTD/CTEP IND agents and other significant NCI DCTD/CTEP initiatives for the ETCTN.
• Clinical Trial Development and Operations Core - This functional component should provide scientific expertise and operational efficiency for a team-science approach for the development of clinical trials and their conduct in the ETCTN. This core also includes a statistical component to appropriately address clinical trial design, implementation, monitoring, and analysis.
• Member Site Accrual and Performance Core - This functional component should provide robust accrual to ETCTN trials by the LAO and its member institutions/sites, including trials led by the LAO applicant and those led by other ETCTN LAOs. This component also provides oversight of the performance of member institutions/sites with respect to both accrual and trial conduct. 

Investigators proposing NIH-defined clinical trials may refer to the Research Methods Resources website for information about developing statistical methods and study designs.

See Section VIII. Other Information for award authorities and regulations.

Section II. Award Information

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

1. Eligible Applicants

Higher Education Institutions - Includes all types 

• 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 

Small Businesses 

• For-Profit Organizations (Other than Small Businesses)

Federal Governments

• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

• 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
• Regional Organizations
• Non-domestic (non-U.S.) Entities (Foreign Organizations)
   

Eligible institution/organization for the purposes of this application is defined as an academic center/organization in the United States or Canada providing direct medical care to patients that is considered one integral organizational entity under a single financial management system and governance structure. A center/organization (e.g., an academic hospital and/or academic clinic program) for this application is distinguished from large medical centers whose primary mission is patient care. In addition to patient care, academic centers/organizations have comprehensive medical training programs, investigational pharmacies, advanced imaging facilities, and preclinical laboratories that perform basic research. 

The only Non-domestic (non-U.S.) Entities (Foreign Institutions) allowed in response to this NOFO are Canadian Institutions. 

Foreign Organizations/Foreign Collaborations

Non-domestic (non-U.S.) Entities (Foreign Organizations) are eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are not allowed. 

NIH will no longer issue awards (i.e., new, renewal, or non-competing continuation) to domestic or foreign entities that involve foreign subawards/subcontracts. All NIH-funded research involving foreign subawards/subcontracts must be submitted in response to a NOFO that is specifically designated for funded international collaborations. See NIH Grants Policy Statement 16.8 Collaborative International Research Awards.

Applications involving foreign subawards/subcontracts submitted in response to this NOFO will be deemed noncompliant and will not be considered for funding. This policy applies to all monetary international collaborations resulting in foreign subawards/subcontracts, however, it does not preclude unfunded international collaborations or foreign components, funding for foreign consultants, or procurement of unique equipment or supplies from foreign vendors.

Applicant Organizations

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 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. Foreign organizations must obtain a NATO Commercial and Government Entity (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.

All PD(s)/PI(s) must be registered with ORCID. The personal profile associated with the PD(s)/PI(s) eRA Commons account must be linked to a valid ORCID ID. For more information on linking an ORCID ID to an eRA Commons personal profile see the ORCID topic in our eRA Commons online help.

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.

Any individual designated as a PD/PI on an application for this ETCTN Lead Academic Organization (LAO) NOFO must not be a PD/PI on an application for any other ETCTN LAO or for the ETCTN Pharmacokinetic Resource Laboratory (U24 Clinical Trials Not Allowed) RFA-CA-27-017.

If the ETCTN LAO application contact PD/PI is not a practicing physician, a practicing physician(s) must be designated to be responsible for overseeing the clinical trials and patient management. This practicing physician must have primary affiliation with the institution submitting the application(i.e., the LAO institution).

2. Cost Sharing

This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement NIH Grants Policy Statement Section 1.2 Definition of Terms.

3. Additional Information on Eligibility

Number of Applications

Only one application per institution (normally identified by having a unique DUNS number or NIH IPF number) is allowed.

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 (in this NOFO, in a policy notice, or other notice from NIH Guide for Grants and Contracts). Conformance to the requirements in the How to Apply - Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Page Limitations

All page limitations described in the How to Apply – Application Guide and the Table of Page Limits must be followed.

For this specific NOFO, the Research Strategy Section is limited to 30 pages.

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.

SF424(R&R) Cover

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.

Facilities & Other Resources: Provide a succinct description of the early phase clinical trial related resources, infrastructure and facilities that are available at the proposed LAO as its roster sites (LAO ICs, AOs, and AO ICs), including but not limited to investigational pharmacies for experimental agents, state-of-the art radiological imaging, radiotherapy delivery, and biospecimen procurement and handling facilities.

Other Attachments: ETCTN LAO applicants must provide the following attachments. Applications that do not include these attachments will be deemed incomplete and withdrawn by CSR before review. The filename provided must be used for each attachment, as it will become a bookmark in the application.

Attachment 1. Organizational Chart, Logistical Planning, and ETCTN LAO Roster (use filename OrgChartandRoster)

• Outline the organizational structure for the ETCTN LAO. Describe how the LAO will identify and develop Request for Collaborative Research under CTEP IND Agent(s) for submission to DCTD/CTEP. Describe how the LAO will identify and assign personnel who have sufficient expertise and committed time to complete key roles on the Request for Collaborative Research under CTEP IND Agent(s), including how statisticians will be involved in trial design. Explain how the LAO will provide oversight of trial proposals, submission, development, conduct, and analysis.
• In particular, describe how the LAO will interact with the DCTD/CTEP clinical trial writing service and/or author its own protocols and include the LAO's plans for addressing delays in protocol development. Note any process differences for trials developed by investigators affiliated with the main LAO institution versus any AO institutions.
• For the LAO Roster, a table should be used to describe the individual sites by type along with their potential for patient accrual. The table should have column headings for Site Name, Site Address, CTEP Site Code (if available), Site Type (LAO, LAO IC, AO, AO IC), Site Leader, Proposed Annual Accrual to ETCTN studies At That Site, and Proposed Estimate of Total Number of Request for Collaborative Research under CTEP IND Agent(s) Submitted by PIs At That Site (e.g., the number submitted over the 6-year project period, not annual). Site types include the main LAO site (LAO), any integrated components for the LAO (LAO IC), any proposed AOs (AO), and any proposed integrated components for those AOs (AO IC). The site leader for the LAO or AO should also serve as the site leader for any ICs for those respective organizations. 
• For LAO applicants from Canada : Describe how the Canadian LAO will carry out all regulatory filings, agreements, and other activities required to develop, lead, and participate in ETCTN clinical trials in accordance with applicable Canadian and US regulations. Describe how trial specimens will be transferred between US and Canadian sites in accordance with ETCTN protocol requirements.

Attachment 2. Communications Information (use filename Communications)

• Outline existing (in-place) routines for the team periodic meetings (weekly, monthly, quarterly, biannual, ad hoc etc.) to monitor patients as trial participants and discuss safety, trial conduct, summaries and evaluations of trial progress. Include also ongoing efforts to ensure timely publication of study results.

Attachment 3. Regulatory Data (use filename RegulatoryInformation):

• Describe how the LAO and any AOs (with their integrated components, if applicable) will conduct, record, monitor, and report trial activities for all patients enrolled to ETCTN trials in accordance with the protocol, NCI DCTD/CTEP policies, standard operating procedures (SOPs), Good Clinical Practice (GCP), and applicable regulatory requirements.

Attachment 4. Standard Operating Procedures Data (use filename ListSOPs)

• Provide a List of Relevant Standard Operating Procedures (SOPs) and organization policies to be used by the ETCTN LAO and AOs for clinical research activities. Items on the list may include, but are not limited to: specimen acquisition and handling; tumor banking procedures and policy; local institution policies (include Institutional Review Board (IRB) policies for Canadian sites only); assay validation procedures; etc. Operational plans, actual detailed SOPs, investigational agent management procedures, and related policy documents should not be provided.

Attachment 5. Capabilities and Performance (use filename CapabilityPerformance)

Data on the capabilities and available resources for specific functional units of the ETCTN LAO applicant should be provided in this Attachment. Relevant, optional information may be provided in tabular form as listed below. Use of the tables is encouraged with clear column headings to describe content. Furthermore, it is suggested that applicants limit the information listed to the top 50 trials and provide only summary information/numbers for the remaining studies. Please use rolling headers for multi-page tables and provide summary totals when applicable.

• "Completed and Ongoing Phase 0, Phase 1, Phase 2, and Pilot Clinical Trials": List early phase clinical trials that have been completed during the last 5 years (2020 through 2024) led by the LAO and any ongoing clinical trials led by the LAO as of 2/28/2025 for which significant research findings are available. Include first-in-human studies and trials that determined dose and schedule for both single agents and investigational agent combinations. For each trial listed, provide trial number and title, exact trial phase, number of patients enrolled, total target sample size for the trial, and respective National Clinical Trial identifier (NCT number).
• "Other Scientific Achievements for Clinical Trials": List early phase clinical trial scientific achievements that have occurred during the last 5 years (2020 through 2024).
• "List of Molecular Characterizations Performed During Conduct of Early Phase Clinical Trials": Describe biomarker assays, molecular characterization, and other correlative laboratory studies performed on patient tissue during the last 5 years (2020 through 2024), especially those that included surgical or image-guided biopsies.
• "Summary Accrual of Enrolled Patients on Early Experimental Therapeutic Clinical Trials": Use a table to describe the number of patients enrolled on early phase clinical trials by the LAO and its rostered sites when the trial was led by ETCTN LAO applicant from 2020 through 2/28/2025. Patient numbers should be listed by trial along with the trial number, trial title, trial phase, and NCT number. A similar table should be used to show the number of patients enrolled by the LAO applicant and its rostered sites when the applicant LAO did not lead the trial.
• "Operational Timelines for Activation of Clinical Trial Proposals": List timelines for the activation of clinical trials between 2020 and 2024 that were led by the applicant LAO (or one of its roster AOs or ICs). List actual timelines for specific steps in the clinical trial protocol development process (i.e., date of  Request for Collaborative Research under CTEP IND Agent(s) review at DCTD/CTEP (start of OEWG timeline), date of final Request for Collaborative Research under CTEP IND Agent(s) approval by DCTD/CTEP, date of trial activation, total elapsed time from initial date Request for Collaborative Research under CTEP IND Agent(s) review to activation) along with total accrual, study duration to date, and note submission of any abstracts and manuscripts, if applicable. Detailed information on primary scientific achievements on trials should be provided in Attachment 6 described below. LAO applicants with no prior ETCTN experience should use equivalent time-points for their past trial development experience.
• "Inclusion Enrollment": Provide one summary table for total accrual for all early phase clinical trials completed over the past 5 years (2020 through 2024) broken down by race, ethnicity, and sex (using the 1997 OPM categories currently in use by NIH).

Attachment 6: Important Primary Scientific Achievements (use filename: PrimaryAchievements):

• In this attachment, document important primary scientific achievements of the proposed LAO and any AOs reported between 3/1/2020 and 2/28/2025. Important primary scientific achievements refer to the primary endpoint(s) for an ETCTN trial led by the LAO/AO and specified in the protocol document. Use a table to show this information with column headings for the NCT ID and NCI CTEP Study ID, Brief Study Title, Trial Phase, Disease Area, Investigational Agent(s), Year of Publication of Primary Endpoint, Manuscript or Abstract Reference, Trial Activation and Closure Dates, Total Accrual, and Brief Description of Importance. Briefly describe the importance regardless of whether the trial was positive or negative. Include the date range as a sub-heading above the table. For applicants with no prior participation in the ETCTN, equivalent information should be provided with notation of the type of organization that conducted the trial. 

SF424(R&R) Senior/Key Person Profile

All instructions in the How to Apply - Application Guide must be followed.

Designate an appropriately qualified PD/PI (or multiple PDs/PIs) for the proposed ETCTN LAO.  For applications with multiple PDs/PIs, applicants may wish to consider designating a PD/PI as primarily responsible for phase 1 trials and another primarily responsible for phase 2 trials.

The LAO and/or its AO(s) should identify at least one statistician with the skill and expertise in the design and monitoring of early phase clinical trials including adaptive and other designs for phase 1 and 2 trials to support the clinical activities of the site or consortium. Proposed ETCTN sites are expected to have the requisite statistical expertise for trial design/monitoring and coordinating patient enrollment on all clinical trials open in the ETCTN.

Sites with a unique interest in the development of therapeutic radiopharmaceuticals in combinations with CTEP-IND agents are encouraged to include radiation oncologists as key personnel.

For each LAO-based team, the applicant may wish to consider designating Senior/Key Persons in the following categories, as needed for the LAO's drug development goals:

• Translational Scientists who will oversee translational efforts and has expertise in biomarker incorporation into early phase clinical trials
• Biostatistician(s) who will be responsible for the statistical design and management of ETCTN studies led by the LAO
• Disease-Focused Clinical Investigator(s) with disease-specific early phase clinical trials expertise responsible for select ETCTN trials in their disease-focused area
• Interventional Radiologists who will be responsible for supervision of acquisition of research biopsies at the LAO and participate in quality/risk improvement initiatives
• Research Pathologists who will be responsible for processing and performing quality review of research biopsy specimens & participate in quality improvement initiatives
• Physician(s) responsible for patient management if the ETCTN LAO PD/PI is not a practicing physician

For each participating AO, the applicant may wish to consider designating Senior/Key Persons in the following categories, as needed:

• AO site leader who will also serve as a Disease-Focused Clinical Investigator at the given site
• Disease-Focused Clinical Investigators with disease-specific early phase clinical trials expertise, responsible for participating in ETCTN studies in their disease area
• Interventional Radiologists who will be responsible for the acquisition of research biopsies at the AO site

R&R Budget

All instructions in the How to Apply - Application Guide must be followed.

The requested budgets should take into consideration the standardized central operational, regulatory and administrative support that will be provided to ETCTN LAO awardees by NCI. These services will be directly funded by the NCI and respective cost must not be included in the LAO requested budgets.

Senior/Key Persons and Other Personnel. Costs should include estimated costs of salary support (based on level-of-effort) for the PD(s)/PI(s) and other Senior/Key Persons responsible for various aspects of early drug development (but not personnel costs directly related to the conduct of clinical trials at the clinical level).

Each individual designated as a PD/PI must commit a minimum of 1.2 person-months of effort per year. This minimal effort level must be maintained throughout the entire project period.

Other designated Senior/Key Persons (e.g., Disease-Focused Clinical Investigators, Translational Scientists, Interventional Radiologists, Research Pathologists) are expected to commit a minimum of 0.6 person-months of effort each per year. Senior/Key Biostatisticians for the LAO may warrant a higher level of commitment of up to 1.2 person-months of effort per year or more depending on the number of trials the LAO expects to lead. Senior/Key Persons should receive partial salary support. The effort level requested should be commensurate with the projected scale of accrual to and opening of clinical trials.

General determination of level of overall funding. The applicant can allocate the total cost amount across all allowable cost categories in any amount or distribution pattern that the applicant believes is appropriate. The applicant can request more (or less) than the estimated amounts with appropriate budget justification. However, budgets are based on estimated ranges costs associated with enrollment of patients on a per-case basis. To justify the budget, the applicant needs to describe in detail in the budget justification the number of patients expected to be accrued for treatment trials in the category of treatment intervention, and for one patient biospecimen collection (including cost of a research biopsy) for each enrollment of a patient on a treatment trial at the various participating sites on the LAO's roster.

The budget should also include funding to be allocated to support research and development, and ETCTN collaboration (in addition to support for scientific leadership, administrative and regulatory activities, data analysis, etc.). All costs for Electronic Medical Record (EMR) builds to launch early phase clinical trials as well as mailing or handling research-related patient specimens, forms, and materials should be included. Other consulting costs should be outlined. Costs for non-accrual activities such as protocol development, statistics and data analysis, protocol submissions to the NCI CIRB (or other IRB for Canadian sites), amendment distribution and continuing review, site training, pharmacy set-up, and site administration for the institution(s) to support participation in early-phase experimental therapeutic clinical trials should be included. It is anticipated that each LAO might submit up to 2 Request for Collaborative Research under CTEP IND Agent(s) per quarter with 3 to 4 Request for Collaborative Research under CTEP IND Agent(s) approved for further development annually. An annual accrual rate of at least 80 to 100 patients per year by the entire LAO roster should be assumed. It is also assumed about 30% of the total accrual would come from ETCTN trials not led by the applicant LAO but by other ETCTN LAOs in the network.

Provide the cost for each main budget category (personnel, supplies, travel, etc.) as appropriate. Costs of the integration of the informatics system with the services provided by the NCI DCTD/CTEP Clinical Trials Monitoring Service (see: http://ctep.cancer.gov/branches/ctmb/resources.htm) and/or costs for additional on-site data management may be included but only for very well-justified on-site expenses.

Funds for travel. Funding should be budgeted for the ETCTN LAO PD(s)/PI(s) to travel to two meetings per year, with one being the NCI/CTEP Early Drug Development (EDD) meeting. Travel funds for four representatives from the ETCTN LAO, AO, and/or IC sites [exclusive of the ETCTN LAO PD(s)/PI(s)] to attend the NCI/CTEP Early Drug Development (EDD) each year should be provided as well as travel costs for two presenters to major national/international meetings per year.

Clinical Trials Research Operations and Research Related Hospital Charges. Requested funds for clinical trials operations must be to support institutional costs of research that are not considered a cost of treatment by medical insurers, and therefore are not reimbursed by insurers (e.g., blood and urine collection and shipping, tumor tissue handling and shipping to the tissue bank, performing research biopsies, performing research imaging studies, etc.). The anticipated total annual expenses for these costs should be based on per-patient costs of the accrual, assuming at least 80 to 100 patients per year and should be broken out by category (e.g., tissue acquisition consisting of research biopsies, tissue handling, shipping of tissues, research imaging studies, etc.). It is anticipated that studies would have on an average 1 to 2 biopsies per patient over the course of a trial.

Provide a detailed breakout of costs used to estimate the per-patient accrual costs in the budget justification. The net per-patient cost for accrual to ETCTN clinical trials regardless of phase (i.e., excluding the costs of laboratory studies) multiplied by the expected number of patients to be accrued (at least 80 to 100 per year) should be approximated as part of the entire budgetary request.

The requested budget items shall NOT include or reflect any costs for the following activities:

• Correlative studies and biomarker assays to enhance specific clinical trials; such studies will be prioritized and supported as needed by separate NCI Administrative Supplements or other funding sources
• NCI provided standardized central operational, regulatory, and administrative support, as these services will be provided by the NCI at no cost to the applicant
• Any costs that are not solely research-related and could be considered "a cost of treatment" by medical insurers

R&R Subaward Budget

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.

PHS 398 Research Plan

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

Specific Aims:

Provide Specific Aims for the entire application. Include key benchmarks such as expected number of clinical trials (by phases) and participant accrual levels.

Research Strategy:

Organize the Research Strategy with sub-sections aligned with each of the functional components/elements listed below. Start each sub-section with the appropriate functional component/element heading.

Sub-Section A: Overview

• Outline the LAO's overall vision and overarching research strategy for the conduct of high-quality, early phase, clinical trials evaluating experimental therapeutic anticancer agents in the ETCTN. Emphasize how the LAO will build on its prior experience and current expertise to accelerate development of these agents.

Sub-Section B: Organizational Structure and Management Core

• Provide an organizational chart to describe the organization of the LAO and its roster site(s). For multi-institution applications, provide justification for the multi-institutional participation and for the selection of participating institutions (including key selection criteria used to select roster sites).
• Describe the general organizational and governing structure, lines of authority, and decision-making processes of the LAO in the areas of administrative, scientific, statistical design & analysis, and data management, including key leadership roles in these areas. Include plans for replacement of key leadership positions and how leadership transitions would be handled.
• Describe the communications processes for the LAO to communicate with and obtain feedback from key stakeholders across disciplines in the LAO and its roster site(s), if applicable, to meet its objectives for the ETCTN.
• Explain how the LAO will provide senior mentorship to early-stage career investigators (ECIs) in leading general early phase clinical trials and disease-specific early phase clinical trials as well as participating in experimental therapeutic development activities (e.g., “Project Teams”, the Investigational Drug Steering Committee) and other NCI initiatives related to the ETCTN).
• Describe how the LAO interacts with DCTD/CTEP on clinical trial activities (throughout development, conduct, and reporting of results and trial closure).  Explain how the LAO oversees and ensures both registration of trials in clinicaltrials.gov and results reporting per required timelines. Describe the LAO’s oversight for use and compliance with ETCTN authorship guidelines for ETCTN-related publications from investigators at the LAO and its roster sites (See: https://ctep.cancer.gov/initiativesPrograms/docs/ETCTN_Publication_Policy.pdf);

Sub-Section C: Clinical Trial Development and Operations Core

Describe how the LAO provides the scientific expertise and operational efficiency for a team-science approach for the development of clinical trials and their conduct in the ETCTN by addressing the major areas listed below.

Clinical Trial Development

• Describe the procedures used to ensure the timely development of phase 1 and phase 2 trials (including small, randomized phase 2 trials), including biomarker-driven trials using integral, integrated, and/or exploratory biomarkers.
• Address how the timelines for protocol development and trial activation per NCI Operational Efficiency Working Group (OEWG) guidelines are followed and how the LAO and its site(s) work with the NCI DCTD/CTEP services for protocol writing and building clinical trial databases within the CTEP common data management system and the NCI Central Institutional Review Board (NCI CIRB) for human subjects protection/ethics review (or other IRB/Ethics Review Boards for ex-US sites).
• Describe the processes and methods used by Disease-Focused Clinical Investigators at the LAO and its AO(s) to provide  ETCTN site portfolio development of disease-specific, early phase clinical trials.

Statistical Support, Data Management, Data Monitoring and Regulatory Compliance for Clinical Trial Conduct

• Describe the approach to study monitoring used by the study PIs/Team and study statistician(s) including:
  • assessment of patient eligibility and evaluability;
  • timely medical review and assessment of clinical trials data;
  • rapid reporting of treatment-related morbidity;
  • Interim evaluation and consideration of measures of outcome, as consistent with patient safety and good clinical trials practice for early phase clinical trials, including ensuring treatment agent activity assessments are accurate and reliable
  • assessment and implementation of protocol amendments for safety, corrective action plans for accrual issues, and change in trial design (scientific and statistical); and
  • integrating with the DCTD/CTEP Data Monitoring Committee and/or Data Safety Monitoring Board for applicable trials.

Biospecimen/Tissue Acquisition and Molecular Characterization

• Describe plans for collaborate with NCI and NCI s central laboratories [including the NCI Molecular Characterization Laboratory (MoCha) and the National Clinical Laboratory Network (NCLN)], and research networks to characterize patient’s tumors on a molecular level to select appropriate patients for specific treatments, and to explore mechanisms of resistance and response to assist in defining follow-on treatment or determine future combination therapies.  Include information on the following:
  • expertise and proficiency in collecting/acquiring high quality fresh and relevant biopsy specimens for biomarker-based and other studies from a high percentage of patients on trials (even if invasive procedures are required) and coordination with shipping to the ETCTN-specified tumor bank and/or other laboratories for analysis;
  • genomic screening practices to identify potentially eligible patients using NCI central laboratories;
  • planning and implementing appropriate pharmacokinetic (pk) and pharmacodynamic studies using the U24 ETCTN PK Laboratory resource integrated with clinical trials (as well as incorporating pharmacogenomic studies when appropriate);
  • analyzing biospecimens from early phase trials for genomic markers (and other biomarkers) to help define response and resistance to investigational treatments; and
  • evaluations of imaging endpoints in early phase trials.

Sub-Section D: Member Site Accrual and Performance Core

• Describe the overall approach to the LAO to enhance accrual to ETCTN trials across its roster sites, including plans to open ETCTN trials in disease-specific clinics at the LAO and AO site.
• Describe specific plans for robust accrual to ETCTN trials across the network, including rare cancers and accrual from special populations (e.g. minority, the elderly, and young adults);
• Describe the procedures for assembling, recruiting, and maintaining appropriate personnel that will support the execution of clinical trials.
• Describe the LAO’s processes, including benchmarks it uses, to ensure effective interaction, communication, and monitoring of accrual and performance within the LAO and its roster sites, including but not limited to:
  • Ensuring roster sites establish and maintain site, investigator, and associate rosters with the Cancer Trials Support Unit (CTSU);
  • Actions to be taken to address failure by investigators and/or institutions to meet accrual targets or other study objectives during trial conduct;
  • Compliance with clinical trial protocol requirements;
  • Timely submission of required data to NCI centralized clinical trial support systems; and
  • Timely preparation, presentation, and publication of clinical trial results and research findings at international meetings and scientific journals by member site investigators.

Sub-section E: Progress Report (for Renewals Only):

• This Progress Report should cover the period of March 1, 2020 through February 28, 2025 and should highlight the most significant achievements of the applicant LAO to the ETCTN in terms of support for trials designed and activated over this period as well as patient enrollment by the LAO and its roster site(s), including both trials led by the applicant LAO and trials led by other ETCTN LAOs). 

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.

Other Research Plan Section: Consortium / Contractual Arrangements

Describe the programmatic, fiscal, and administrative arrangements agreed upon between the applicant LAO institution and any AO(s).  LAO award recipients will be required to submit all agreements to NCI DCTD/CTEP for review.

Other Research Plan Section: Letters of Support

The applicant LAO institution must provide a Letter of Support documenting the following:

• Institutional support for the application, including the willingness to open and conduct ETCTN trials in accordance with the requirements in this NOFO, including rare cancer trials, led by the applicant LAO or one of its AO(s) or another ETCTN LAO.

Each AO institution proposed as part of this LAO application must provide a Letter of Support documenting the following:

• Institutional support for the application, including the willingness to open and conduct ETCTN trials in accordance with the requirements in this NOFO, including rare cancer trials, led by the applicant LAO or one of its AO(s) or another ETCTN LAO.

Other Plan(s): 

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

• A Data Management and Sharing Plan (DMS Plan) is required for any NIH-funded or conducted research that will generate scientific data. Applicants must submit the DMS Plan at the time of application using the NIH DMS Plan Format Page. The DMS Plan must address the elements in the structured format should not exceed two (2) pages. Where the DMS Plan Format Page requires a “Yes or No” response, no additional narrative is allowed.

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.

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.

Given that applicants should not propose any specific clinical trials at the time of application, the Study Record should NOT be completed.

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start). All instructions in the How to Apply - Application Guide must be followed.

The following additional instructions are provided for Delayed Onset Study section for this NOFO:

• All applicants must add and complete a single Delayed Onset Study record and must check the box for “Anticipated Clinical Trials?”
• For Study Title – Use “Multiple Delayed Onset Studies”
• For the Justification Attachment – Indicate that during the project period, multiple delayed onset clinical trials will be designed, reviewed through standard NCI procedures, and, if approved, conducted by the ETCTN LAO applicant. Briefly describe the general approach that the applicant will take to address the relevant review criteria related to protection of human subjects and the related NIH policies.

PHS Assignment Request Form

All instructions in the How to Apply - Application Guide must be followed.

Foreign Organizations

Foreign (non-U.S.) organizations must follow policies described in the NIH Grants Policy Statement, and procedures for foreign organizations described throughout the How to Apply Application Guide.

3. Unique Entity Identifier and System for Award Management (SAM)

See Part 2. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

4. Submission Dates and Times

Part I. contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time.  If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the How to Apply – Application Guide.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement Section 7.9.1 Selected Items of Cost.

7. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the How to Apply - Application Guide. Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply – Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile form. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this NOFO for information on registration requirements.

The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the How to Apply - Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed. 

Recipients or subrecipients must submit any information related to violations of federal criminal law involving fraud, bribery, or gratuity violations potentially affecting the federal award. See Mandatory Disclosures, 2 CFR 200.113 and NIH Grants Policy Statement Section 4.1.35.

Send written disclosures to the NIH Chief Grants Management Officer listed on the Notice of Award for the IC that funded the award and to the HHS Office of Inspector Grant Self Disclosure Program at grantdisclosures@oig.hhs.gov. 

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in the policy

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process.  Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

For this particular NOFO, note the following: 

This section includes the standard NIH review criteria for all NOFOs that include clinical. However, as noted in the description and application information sections, no specific clinical trials should be proposed as part of this application. The review criteria will be applied to the applicant's capabilities/expertise, staffing, resources, and research strategy for the design, development, conduct, monitoring, and analysis of multiple, delayed onset, early phase clinical trials to accelerate development of NCI DCTD/CTEP IND anticancer agents over the course of the project period. 

A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Reviewers will consider each of the review criteria below in the determination of scientific merit and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by CSR , in accordance with NIH peer review policies and practices, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications will receive a written critique.

May undergo a committee process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.

Requests for reconsideration of initial peer review will not be accepted for applications submitted in response to this NOFO. 

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this NOFO. Following initial peer review, recommended applications will receive a second level of review by the National Cancer Advisory Board. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement Section 2.5.1. Just-in-Time Procedures. This request is not a Notice of Award nor should it be construed to be an indicator of possible funding.

Prior to making an award, NIH reviews an applicant’s federal award history in SAM.gov to ensure sound business practices. An applicant can review and comment on any information in the Responsibility/Qualification records available in SAM.gov.  NIH will consider any comments by the applicant in the Responsibility/Qualification records in SAM.gov to ascertain the applicant’s integrity, business ethics, and performance record of managing Federal awards per 2 CFR Part 200.206 “Federal awarding agency review of risk posed by applicants.”  This provision will apply to all NIH grants and cooperative agreements except fellowships.

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement Section 2.4.4 Disposition of Applications.

Section VI. Award Administration Information

1. Award Notices

A Notice of Award (NoA) is the official authorizing document notifying the applicant that an award has been made and that funds may be requested from the designated HHS payment system or office. The NoA is signed by the Grants Management Officer and emailed to the recipient’s business official.

In accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Any pre-award costs incurred before receipt of the NoA are at the applicant's own risk.  For more information on the Notice of Award, please refer to the NIH Grants Policy Statement Section 5. The Notice of Award and NIH Grants & Funding website, see Award Process.

Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.

ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain “applicable clinical trials” on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm

Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).

2. Administrative and National Policy Requirements

The following Federal wide and HHS-specific policy requirements apply to awards funded through NIH:

• The rules listed at 2 CFR Part 200, Uniform Administrative Requirements, Cost Principles, and Audit Requirements for Federal Awards.
• All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the terms and conditions in the Notice of Award (NoA). The NoA includes the requirements of this NOFO. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities.

All federal statutes and regulations relevant to federal financial assistance, including those highlighted in NIH Grants Policy Statement Section 4 Public Policy Requirements, Objectives and Other Appropriation Mandates.

By applying for or accepting federal funds from HHS, recipients certify compliance with all federal antidiscrimination laws and these requirements and that complying with those laws is a material condition of receiving federal funding streams. Recipients are responsible for ensuring subrecipients, contractors, and partners also comply.

Applicants and recipients are strongly encouraged to refer to the NIH Director’s Statement of Priorities, entitled “Advancing NIH’s Mission Through a Unified Strategy.” 

Recipients are responsible for ensuring that their activities comply with all applicable federal regulations. Pursuant to 2 CFR 200.340, by accepting an NIH award, the recipient agrees that continued funding for the award is contingent upon the availability of appropriated funds, recipient satisfactory performance, compliance with the Terms and Conditions of the award, and may also otherwise be terminated, to the extent authorized by law, if the agency determines that the award no longer effectuates the program goals or agency priorities, in line with 2 CFR 200.340(a)(4).

Pursuant to the Cybersecurity Act of 2015, Div. N, § 405, Pub. Law 114-113, 6 USC § 1533(d), the HHS Secretary has established a common set of voluntary, consensus-based, and industry-led guidelines, best practices, methodologies, procedures, and processes.

Successful recipients under this NOFO agree that:

When recipients, subrecipients, or third-party entities have:

• ongoing and consistent access to HHS owned or operated information or operational technology systems; and
• receive, maintain, transmit, store, access, exchange, process, or utilize personal identifiable information (PII) or personal health information (PHI) obtained from the awarding HHS agency for the purposes of executing the award.

Cybersecurity plans and procedures must at minimum include the following:

• Develop cybersecurity plans and procedures, modeled after the NIST Cybersecurity framework, to protect HHS systems and data:
  • Identify:
    • Develop an inventory of all assets and accounts with access to HHS owned and operated information or operational technology systems or which obtain PII or PHI for the purposes of the award.
  • Protect:
    • Limit access to HHS owned and operated systems to only those in need of access to complete reward activities.
    • Require all staff to complete annual cybersecurity and privacy awareness training. Visit 405(d): Knowledge on Demand (hhs.gov) to obtain free trainings, if needed.
    • Enable multifactor authentication for all employees, subrecipients, and third-party entities to access HHS owned and operated information or operational technology systems.
    • Regularly backup sensitive data and test backups.
  • Detect:
    • Install anti-virus or anti-malware software on all devices, servers, and accounts used to connect to HHS owned and operated systems.
  • Respond:
    • Develop an incident response plan. See Incident-Response-Plan-Basics_508c.pdf (cisa.gov) to learn about developing incident response plans.
    • Have cybersecurity incident reporting procedures that ensure the relevant HHS awarding agencies are notified of a cybersecurity incident within 48 hours of discovery. A cybersecurity incident is defined as an unplanned interruption to a technology service or reduction in the quality of a technology service, or an occurrence that actually or potentially jeopardizes the confidentiality, integrity, or availability of an information system or the information the system processes, stores, or transmits.
  • Recover:
    • Investigate incidents and plug any security gaps identified. 

All activities proposed in your application and budget narrative must align with applicable law, including but not limited to statutes, executive orders, federal regulations and applicable judicial holdings.  Accordingly, discretionary awards shall not be used to fund, promote, encourage, subsidize, or facilitate; racial preferences or other forms of racial discrimination by the recipient, including activities where race or intentional proxies for race will be used as a selection criterion for employment or program participation; denial by the recipient of the sex binary in humans, or the belief that sex is a chosen or mutable characteristic; illegal immigration; or any other initiatives that compromise public safety.  If an application does not align, the application will not receive funding to the extent permitted by law and applicable court orders.

For applications involving substance abuse, the application must not support harm reduction. Please see Updated Funding Guidance for Recipients on Supplies and Services.

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (HHS) grant administration regulations at 2 CFR Part 200, and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the recipients is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the recipients for the project as a whole, although specific tasks and activities may be shared among the recipients and NIH as defined below.

The PD(s)/PI(s) will have the primary responsibility for:

• Establishment of an overall research strategy for clinical trial development across a range of cancer types, modalities, and treatment approaches using NCI DCTD/CTEP IND agents. Ensuring that senior investigators, including Disease-Focused Clinical Investigators, clinical investigators, interventional radiologists, research pathologists, and others as applicable lead and/or participate in multidisciplinary scientific teams during the development and implementation of the ETCTN Drug Development Plans and proposals.
• Oversight of the submission of Letters of Intent for all proposed LAO/AO trials and protocol  development of all approved Letters of Intent along with the overall management of the conduct, monitoring, and results reporting for early phase ETCTN clinical trials led by the LAO or its AO roster site(s).
• Oversight of conduct of all the LAO’s roster sites (i.e., LAO, LAO Integrated Components, Affiliated Organizations (AOs), AO Integrated Components) on all ETCTN trials roster sites participate in, including evaluation of accrual and performance of the sites as well as submission of Letters of Intent for the LAO overall and activated trials on an annual basis.
• Mentoring programs for early-stage career investigators (ECIs) in leading early phase experimental therapeutic trials and associated clinical research activities.
• Ensuring all U.S. LAO roster sites are members of the NCI Central Institutional Review Board (CIRB) and use the NCI CIRB as the IRB of record for all ETCTN clinical trials.
• Provision of standard operating procedures covering all aspects of clinical trial design, trial conduct (including compliance with Good Clinical Practice (GCP) guidelines and risk-based central monitoring for applicable CTEP IND trials), development and compliance with data safety monitoring plans and participation in a Data Monitoring Committee or a Data Safety Monitoring Board designated by NCI DCTD/CTEP for applicable ETCTN trials, and training of LAO and roster site Clinical Research Associates (CRAs) and Study Chairs/Teams about their responsibilities for study trial monitoring.
• Participation in the collective management of the ETCTN, including participation in appropriate ETCTN Program activities and initiatives (e.g., “Project Teams” for new NCI DCTD/CTEP IND agents, the Investigational Drug Steering Committee, trans-ETCTN Biospecimen Working Group or EBWG).
• Compliance with NCI/NIH timelines and policies for registration of and results reporting for ETCTN trials by the LAO of all trials the LAO or one its roster sites leads in clinicaltrials.gov.
• Use of the ETCTN Program's common data management system including use of the NCI DCTD/CTEP infrastructure for the program and reporting tools for adverse event reporting and risk-based central monitoring as detailed in the compliance documents referenced below.
• Compliance with the following NCI DCTD/CTEP policies covering ETCTN trials:
  • NCI Experimental Therapeutics Clinical Trials Network (ETCTN) Guidelines dated November 2024 and any subsequent updated versions available at: (https://ctep.cancer.gov/initiativesprograms/docs/ETCTN_Program_Guidelines.pdf).
  • NCI Registration and Credential Repository (RCR) for all ETCTN investigators available at:  https://ctep.cancer.gov/investigatorResources/default.htm
  • NCI DCTD/CTEP Pharmaceutical Management Policies (PMB) available at https://ctep.cancer.gov/branches/pmb/default.htm - including the requirement to use the PMB centralized agent inventory management system, AURORA, for ordering, receipt, use, and tracking of NCI DCTD/CTEP IND agents for use in ETCTN trials available at: https://ctep.cancer.gov/branches/pmb/aurora.htm.
  • NCI Guidelines for Monitoring the Experimental Therapeutics Clinical Trials Network (ETCTN) and other Early Phase CTMS-Monitored Studies (which includes information on auditing as well) available at: https://ctep.cancer.gov/branches/ctmb/clinicalTrials/docs/ETCTN_Monitoring_Guidelines.pdf and the NCI Guidelines for Investigators: Adverse Event Reporting Requirements for DCTD (CTEP and CIP) INDs and IDEs available at: (https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/aeguidelines.pdf)
  • NCI/DCTD CRADA agreements, and the Intellectual Property Option to Collaborators for ETCTN trials under CTEP IND/IDE regulatory sponsorship available at: (https://ctep.cancer.gov/branches/rab/intellectual_property_option_to_collaborators.htm).
• Compliance with ETCTN Program policy to ensure that LAO and its roster site(s) have the ability to participate in ETCTN trials led by other ETCTN LAOs.
• Recipients will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies and within the limits of any accepted binding NCI/NIH collaborative agreements with biotechnology and as governed by NCI-approved Data Management and Sharing Plans and NCI approved review for use of biospecimens collected in association with ETCTN trials.

NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards. The substantially involved NCI program staff member(s), acting as Project Scientist(s), will coordinate in a centralized fashion the various activities of the recipients. Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. Specific responsibilities of the NCI Project Scientist(s) will include:

• Responsibility for ensuring trials proposed are within the research scope of the ETCTN Program.
• Facilitating and coordinating evaluation and final review decisions by the NCI DCTD Protocol Review Committee on  Request for Collaborative Research under CTEP IND Agent(s) as well as review of protocol documents for approved Request for Collaborative Research under CTEP IND Agent(s) and subsequent revisions and amendments.
• Coordinating actives for evaluation of “Project Team” proposals by the NCI Investigational Drug Steering Committee.
• Performing all the roles and responsibilities as the agent(s) sponsor as defined in the Code of Federal Regulations for ETCN clinical trials under NCI DCTD/CTEP IND and/or IDE regulatory sponsorship.
• Working with ETCTN LAO recipients to collaboratively manage issues associated with their participation in the conduct of clinical trials across the network.
• Informing the PDs/PIs of scientific opportunities resulting from NCI-supported clinical research programs and facilitating collaborations between the ETCTN and other NCI-sponsored programs.
• Advising recipients concerning mechanisms established by the recipients for quality control of therapeutic and diagnostic modalities.
• Oversight of data and safety monitoring plans and/or Committees or Boards for ETCTN clinical trials. Oversight of onsite auditing programs and quality assurance programs for the ETCTN Program, including oversight of core services for radiotherapy and imaging support in ETCTN trials.
• Review proposals from ETCTN investigators for correlative studies to enhance clinical trials and recommend approved studies for funding consideration with CRADA partners and/or other sources.
• Review collection and distribution of biospecimens collected in association with ETCTN trials per approved protocol as well as review additional requests for use of biospecimens collected in association with ETCTN trials after activation.
• Ensuring compliance with FDA requirements for investigational agents and ensuring compliance with OHRP and other federal regulations for research involving human research subjects including compliance with Good Clinical Practice (GCP) guidelines for ETCTN IND trials.
• Reviewing the overall accrual and performance of all recipient’s sites as well as by trial and periodically evaluating funding needs for patient accrual.

NCI will have access to all data collected and/or generated under this Cooperative Agreement and may periodically review the data.NCI reserves the right to reduce the budget or withhold an award in the event of substantial recipient under-performance or other substantial failure to comply with the terms of award.

Areas of Joint Responsibility include:

• General aspects of collaboration on study development and conduct especially with respect to compliance with federal regulations for clinical trial research (e.g., ensuring that when new avenues of cancer therapy involving investigational drugs are pursued, trials are designed appropriately per IND application to the FDA).
• Participate as active team members on drug development “Project Teams” led by CTEP Medical Officers and provide input for the Investigational Drug Steering Committee (IDSC) with respect to the drug development plans. The IDSC under the NCI Coordinating Center for Clinical Trials (CCCT) faciliates collaborations with the NCI in the design and prioritization of early phase drug development trials carried out within the ETCTN. 
• The IDSC will consist of the following voting members:
  • The PD(s)/PI(s) of each awarded CTEP’s ETCTN UM1 center will collectively have one vote.
  • The PD(s)/PI(s) of each awarded PK U24 laboratory will collectively have one vote.
  • Representative(s) from each NCTN group will collectively have one vote.
  • The subject matter experts in trial design, clinical imaging, radiation therapy, radiation therapy, pharmacokinetics/pharmacodynamics, cancer omics, health-related quality of life, and biostatistics will collectively have one vote.
  • The patient advocate(s) will collectively have one vote.
  • The NCI staff members will collectively have one vote.
• Additional NIH/NCI program staff and other government staff may participate in IDSC meetings as non-voting members.
• Two PD(s)/PI(s) will be elected to serve as co-chairs of the IDSC on a rotating basis following award issuance. All IDSC decisions and recommendations that require voting will be based on a majority vote. The IDSC provides recommendations for consideration by CTEP Program Officials.
• The Steering Committee may have additional non-voting members.
• Establish a transition plan to transfer data and procedures in the case that the PK Laboratory transitions to a new recipient after the conclusion of the award.
• Discuss and resolve any issues raised during the initial review of Letters of Intent for new trial proposals.
• Review recommendations from the NCI Clinical Trials and Translational Research Advisory Committee (CTAC) on strategic directions for the ETCTN Program.
• Review ongoing ETCTN trial development and conduct jointly on a periodic basis depending on the trial phase and safety monitoring parameters.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between recipients and NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual recipient. This special dispute resolution procedure does not alter the recipient's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and HHS regulation 45 CFR Part 16.

3. Data Management and Sharing

A Data Management and Sharing Plan (DMS Plan) is required for any NIH-funded or conducted research that will generate scientific data. Applicants must submit the DMS Plan at the time of application using the NIH DMS Plan Format Page. The DMS Plan must address the elements in the structured format should not exceed two (2) pages. Where the DMS Plan Format Page requires a “Yes or No” response, no additional narrative is allowed. 

4. Reporting

When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement Section 8.4.1 Reporting. To learn more about post-award monitoring and reporting, see the NIH Grants & Funding website, see Post-Award Monitoring and Reporting.

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement Section 8.6 Closeout. NIH NOFOs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 2 CFR Part 200.301.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

eRA Service Desk - Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues.

Grants.gov Support Center - Questions regarding Grants.gov registration and services (e.g., Workspace, subscriptions).

NCI ETCTN RFA
National Cancer Institute (NCI)
Telephone: 240-276-5930
Email: NCIETCTNRFA@mail.nih.gov
 

Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).

Office of Grants Administration
National Cancer Institute (NCI)
Telephone: 240-276-6291
Email: NCIFinancialContact@nih.gov 
 

Section VIII. Other Information

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 2 CFR Part 200.