Pediatric Early Phase Clinical Trials Network (UM1)

Pediatric Early Phase Clinical Trials Network (UM1) is sponsored by National Cancer Institute (NCI). Supports institutions to implement and maintain a vigorous pediatric cancer early phase clinical trials program, including expertise in imaging, genomics, and pharmacokinetics.

Expired RFA-CA-17-027: Pediatric Early Phase Clinical Trials Network (UM1) This notice has expired. Check the NIH Guide for active opportunities and notices. Department of Health and Human Services Part 1.

Overview Information Participating Organization(s) National Institutes of Health ( NIH ) of Participating Organizations National Cancer Institute ( NCI ) Funding Opportunity Title Pediatric Early Phase Clinical Trials UM1 Research Project with Complex Structure Cooperative Agreement August 25, 2023 - This RFA has been reissued as RFA-CA-24-007 . July 06, 2017 - Notice of Change in Application Due Date for RFA-CA-17-027.

See Notice NOT-CA-17-072 . Funding Opportunity Announcement (FOA) Number Companion Funding Opportunity Applicant institution may submit only one application as defined in Section III. 3.

Additional Information on Eligibility . Catalog of Federal Domestic Assistance (CFDA) Number(s) Funding Opportunity Purpose The purpose of this Funding Opportunity Announcement (FOA) is to enhance NCI’s program for conducting early phase clinical trials in children with cancer, currently supported as the Children's Oncology Group (COG) Phase 1 & Pilot Consortium.

The overall goal is to ensure that high priority novel agents can be tested in pediatric patients in a timely manner. Towards this end, applications are solicited for the Pediatric Early Phase Clinical Trials Network (PEP-CTN) to continue the clinical research activities now supported through the COG Phase 1 & Pilot Consortium.

The scope of the proposed PEP-CTN should cover the design and conduct of pediatric Phase 1 trials that will be expected to often include Phase 2 expansion cohorts. In addition, the Network will be expected to conduct pilot studies of novel regimens to determine their tolerability so that promising agents/regimens can proceed to definitive testing in Phase 3 clinical trials.

These clinical trials should meaningfully advance pediatric oncology drug development during the award period. The awardee will lead the PEP-CTN Operations and Data/Statistics Center (ODSC) and will interact with selected Core Member institutions and Phase 2 Expansion Institutions on the conduct of early phase clinical trials.

This FOA is designed to enhance the existing program so that the Network can more efficiently and expeditiously develop and implement state-of-the-art early phase clinical trials.

The important changes include: Recognition of the need for seamless transitions from Phase 1 to Phase 2 testing, reflected by the modified initiative name (PEP-CTN) emphasizing "early phase" clinical trials; The establishment of the Pediatric Early Phase (PEP) Agent Prioritization Committee to prioritize agents for evaluation by the PEP-CTN and to expedite the pace at which novel investigational agents enter clinical testing in pediatric patients; The addition of central monitoring for all PEP-CTN clinical Funds to support genomic characterization to establish eligibility and/or treatment assignment for PEP-CTN clinical trials and/or to facilitate factors determining the activity of agents studied by the PEP-CTN.

Applicants responding to this FOA must base their plans for the PEP-CTN institutional accrual base for Network clinical trials on the NCI's intention to include the current member institutions of the COG Phase 1/Pilot Consortium as the PEP-CTN Core Member Institutions.

An additional 20 institutions are expected to be selected post-award to participate in Network clinical trials when additional accrual potential is needed (e.g., for Phase Open Date (Earliest Submission Date) Letter of Intent Due Date(s) 30 days prior to the application due date New Date September 14, 2017, by 5:00 PM local time of applicant organization.

All types of non-AIDS applications allowed for this funding opportunity announcement are due on these dates. 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. AIDS Application Due Date(s) New Date September 15, 2017 per issuance of NOT-CA-17-072 .

(Original Expiration Date: August 17, 2017 ) It is critical that applicants follow the Research (R) Instructions (R&R) Application Guide , except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts ). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced.

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

Part 1. Overview Information Part 2. Full Text of the Announcement I.

Funding Opportunity Description Section II. Award Information Section III. Eligibility Information Section IV.

Application and Submission Section V. Application Review Information Section VI. Award Administration Information Section VII.

Agency Contacts Section VIII. Other Information Full Text of Announcement Section I. Funding Opportunity Description The purpose of this Funding Opportunity Announcement (FOA) is to enhance NCI’s program for conducting early phase clinical trials in children with cancer, currently supported as the Children's Oncology Group (COG) Phase 1 & Pilot Consortium.

The overall goal is to ensure that high priority novel agents can be tested in pediatric patients in a timely manner. Towards this end, the clinical research activities now supported through the COG Phase 1 & Pilot Consortium will be continued (and enhanced) by the Pediatric Early Phase Clinical Trials Network (PEP-CTN).

Investigators responding to this FOA and applying for PEP-CTN award are expected to provide the capabilities needed to implement and maintain a vigorous and scientifically strong pediatric cancer early phase clinical trials program, including: Strong scientific leadership in pediatric drug development, which should include expertise in the application of imaging, genomics and translational biology, and pharmacokinetics to early phase pediatric clinical Ability to ensure timely development of clinical trial protocols; Effective data management, including appropriate Quality Assurance/Quality Control (QA/QC) methods as well as central study monitoring; Regulatory expertise for clinical trials involving investigational agents; and Appropriate expertise and capabilities for statistical design and analysis of early phase clinical trials.

changing landscape of oncology drug development, the key changes incorporated into this FOA in comparison to the current COG Phase 1 & Pilot Consortium An organizational structure to facilitate seamless transitions from Phase 1 to Phase 2 testing; A streamlined prioritization process for identifying novel agents for testing through the PEP-CTN that is intended to reduce the timeline for moving agents into pediatric testing; An enhanced program for study monitoring that builds upon a combination of existing annual on-site audits with the addition of central study monitoring of selected items for all patients; and Incorporation of genomic characterization as an essential component of the PEP-CTN, both for defining eligibility criteria for patients with specific characteristics and for facilitating understanding of observed Investigators proposed by the applicant institution will lead the PEP-CTN Operations and Data/Statistics Center (ODSC) and will interact with selected Core Member Institutions and Phase 2 Expansion Institutions on the conduct of early phase clinical trials.

These clinical trials are expected to meaningfully advance pediatric oncology drug development during the award NCI has historically been the primary source of support for evaluations of new agents and new treatment approaches for children with cancer in the United States.

The support that NCI has provided for early phase clinical trials has resulted in children with cancer having access to a broad range of new anti-cancer agents and has contributed to the identification of curative treatments for approximately 80% of children with cancer. Nonetheless, as many as 20% of children with cancer succumb to their disease, and for selected cancer diagnoses this rate is much higher.

Furthermore, a substantial number of childhood cancer survivors experience significant short- and long-term toxicities and other adverse health effects. Hence, there remains a critical need for safely introducing new agents and new treatment approaches for children with cancer so that children can benefit from advances in cancer biology and drug development.

This ability to quickly and efficiently conduct first-in-children studies is critical to NCI’s overall clinical research program for children with cancer. This FOA represents a continuation of NCI s commitment to childhood cancer research but with updates to accommodate changes in the landscape of oncology drug development.

Overall Goals and Requirements of this FOA The scope of the PEP-CTN will be the design and conduct of pediatric Phase 1 trials that will often include Phase 2 expansion cohorts. As well, the Network will conduct pilot studies of novel regimens to determine their tolerability so that they can proceed to definitive testing in Phase 3 clinical trials.

Through these activities, the PEP-CTN will allow high priority novel agents to be introduced into the pediatric oncology setting in a timely manner. Randomized Phase 2 trials will in most cases not be within the purview of the PEP-CTN, but rather will be conducted by the Children’s Oncology Group.

The Pediatric Early Phase (PEP) Agent Prioritization Committee will be established by NCI to prioritize agents for evaluation by the PEP-CTN. The goal for the Committee is to address a critical need within the childhood cancer research community by providing for the timely, rigorous, and transparent prioritization of agents under development for adult cancers for evaluation in the pediatric setting.

The Committee will be led by the PEP-CTN Chairperson, and membership will include a range of pediatric drug development stakeholders (see Joint Responsibilities in Section VI. 2 Cooperative Agreement Terms and Conditions ).

Requests for evaluation of agents for early phase clinical testing through the PEP-CTN will be accepted for review by the PEP Agent Prioritization Committee from PEP-CTN members, COG Disease Committees, pharmaceutical companies, and others. Agents prioritized by the Committee will have protocols rapidly developed by the PEP-CTN that will then be reviewed by CTEP to ensure that all safety and regulatory issues have been addressed.

The process will be expedited by the use of protocol templates developed by the PEP-CTN and approved by CTEP for Phase 1, Phase 1-2, and pilot studies. By providing a single pathway for agents to enter the PEP-CTN and by using pre-approved templates for protocol development, the time previously spent in multiple levels of review for Letter of Intent (LOI) submission and approval will be reduced.

The process also provides greater transparency for the agent prioritization process for NCI-supported pediatric early phase clinical trials and provides a single portal by which pharmaceutical companies can propose agents for pediatric early phase clinical evaluation in collaboration with NCI and NCI-supported investigators.

The PEP-CTN will need to have the ability to identify patients with specific genomic alterations for its clinical trials. The PEP-CTN will also be expected to collect tumor tissue on all patients enrolled on its clinical trials and as well to collect specimens suitable for analyzing for circulating tumor DNA (ctDNA).

Funds for genomic testing of selected specimens will be provided to the PEP-CTN for use for single gene or gene panel sequencing to determine eligibility and for more extensive sequencing (e.g., whole exome and RNAseq) to identify genomic characteristics associated with response (or lack thereof). To meet regulatory expectations, the PEP-CTN will have an enhanced program for study monitoring.

This program will be built upon a combination of the existing annual on-site audits with the addition of central study monitoring of selected items for all patients. The on-site audits will continue to be supported by NCI through Theradex, and funding will be provided to the PEP-CTN to support central study monitoring.

Applicants will be expected to have appropriate capabilities for preparing and submitting Investigational New Drug Applications (INDs) in support of Network clinical trials and for meeting the regulatory responsibilities associated with being a study sponsor.

This is a critical capability so that the PEP-CTN can encourage pharmaceutical and biotechnology companies to collaborate with the PEP-CTN for agents for which NCI-CTEP does not have a CRADA with the corresponding company. Interactions with Other NCI Clinical Trials Applicants will be required to have experience developing and implementing clinical trials using MediData Rave, the Cancer Trials Support Unit (CTSU, https://www. ctsu.

org/Public/Default. aspx ), and the Oncology Patient Enrollment Network (OPEN) Portal system ( https://open. ctsu.

org/open/logonForm. open ). PEP-CTN clinical trials will be conducted using these clinical trial research services and infrastructures.

PEP-CTN clinical trials will be within the purview of the NCI Central IRB ( https://ncicirb. org/cirb ) , and PEP-CTN Member Institutions will be required to use the NCI Central IRB. PEP-CTN Organization and Functions The governing body for the PEP-CTN will be its Steering Committee, which will set the overall research direction and research procedures of the Network.

Details on the composition and functions of the Steering Committee are provided in Section VI. 2 Cooperative Agreement Terms and Conditions . Applicants will be expected to structure the activities of the proposed PEP-CTN across three main areas: Clinical and Translational Research Program; Operations and Data Management/Statistics; and Member Institutions.

Major responsibilities for each of these areas include the PEP-CTN Clinical and Translational Research Program: Pediatric drug development clinical research program; Genomics and translational biology for PEP CTN clinical trials; Pharmacokinetics program for PEP-CTN clinical trials; and Imaging for PEP-CTN clinical trials.

PEP-CTN Operations and Data/Statistics Center (ODSC) with responsibilities including: Clinical trial protocol development; Data Management/Analysis; Quality Control/Quality Assurance including central data Statistical design and analysis of early phase clinical trials; Regulatory affairs and compliance; Managing tissue acquisition, tissue shipping, and tissue storage Logistical management for PEP-CTN operations, including teleconferences, electronic communications, meetings, etc. PEP-CTN Member institutions: "Core Member Institutions" for participation in all PEP-CTN clinical trials and for the support of PEP-CTN clinical research Phase 2 expansion and pilot institutions for participation in selected clinical trials.

It is expected that the current members of the COG Phase 1/Pilot Consortium will become PEP-CTN Core Member Institutions. Accordingly, applicants should consider these sites and their capabilities. Applicants will be able to invite up to three additional institutions if a scientific leader(s) proposed by the applicant is not at one of these Core Member Institutions.

Importantly, the composition of the Core Member Institutions during the project period is meant NOT to be static but subject to adjustment based on performance evaluation. Therefore, applicants must be able and prepared to conduct rigorous performance evaluation and replace under-performing Core Member Institutions.

The current Core Member Institutions are listed below: Ann and Robert H Lurie Children's Hospital of Chicago Baylor College of Medicine/Dan L Duncan Comprehensive Cancer C’s Mott Children's Hospital Children's Healthcare of Atlanta - Egleston Children's Hospital Colorado Children's Hospital of Alabama Children's Hospital of Los Angeles Children's Hospital of Orange County Children's Hospital of Philadelphia Children's Hospital of Pittsburgh of UPMC Children's National Medical Center Cincinnati Children's Hospital Medical Center Columbia University Medical Center/Herbert Irving Cancer Center Dana-Farber/Harvard Cancer Center National Institutes of Health Clinical Center Riley Hospital for Children Saint Jude Children's Research Hospital Seattle Children's Hospital UCSF Medical Center-Mission Bay University of Minnesota/Masonic Cancer Center Washington University School of Medicine After the PEP-CTN award is made, up to an additional 20 institutions will be selected by the PEP-CTN Steering Committee to participate in PEP-CTN clinical trials when additional accrual potential is needed (e.g., for Phase 2 expansion cohorts).

VIII. Other Information for award authorities and regulations. Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement.

Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.

2 for additional information about the substantial involvement for Application Types Allowed Glossary and the SF424 (R&R) Application Guide provide details on Funds Available and Anticipated Number of Awards NIH intends to fund one award, corresponding to a total of $4,091,000, for fiscal year 2018. Future year amounts will depend on annual appropriations. The applicant may request a budget of up to $3,600,000 annually in direct costs.

The applicant should request support for a project period Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.

Higher Education Institutions Public/State Controlled Institutions of Higher Education Private Institutions of Higher Education The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education: Hispanic-serving Institutions Historically Black Colleges and Universities (HBCUs) Tribally Controlled Colleges and Universities (TCCUs) Alaska Native and Native Hawaiian Serving Institutions Asian American Native American Pacific Islander Serving Nonprofits Other Than Institutions of Higher Education Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Nonprofits without 501(c)(3) IRS Status (Other than Institutions For-Profit Organizations (Other than Small Businesses) Eligible Agencies of the Federal Government U.S. Territory or Possession Non-domestic (non-U.S.) Entities (Foreign Institutions) are Non-domestic (non-U.S.) components of U.S. Organizations are not eligible Foreign components, as defined in the NIH Grants Policy Statement , are allowed but not as Core Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) 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 Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number.

After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application. System for Award Management (SAM) (formerly CCR) 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. Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.

must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants. gov registration.

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 must have an active DUNS number and SAM registration in order to complete the Directors/Principal Investigators (PD(s)/PI(s)) All PD(s)/PI(s) must have an eRA Commons account.

PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Eligible Individuals (Program Director/Principal 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 his/her organization to develop an application for support.

Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH 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 SF424 If multiple PDs/PIs are proposed, these individuals may come from single or multiple institutions.

Applicants may consider, for example, one PD/PI to be responsible primarily for the Clinical and Translational Research Program, who will be acting as Network Chairperson and another PD/PI to be responsible for the Operations and Data/Statistics Center (ODSC). This FOA does not require cost sharing as defined in the NIH Grants Policy Statement . 3.

Additional Information on Eligibility 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.

This means that the NIH will A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission 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 NOT-OD-11-101 ). Section IV. Application and Submission Information Buttons to access the online ASSIST system or to download application forms are available in Part 1 of this FOA.

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 Research (R) Instructions (R&R) Application Guide , including Supplemental Grant Application Instructions except where instructed in this funding opportunity announcement to do otherwise.

Conformance to the requirements in the Application Guide is required and strictly enforced.

Applications that are out of compliance with these instructions may be delayed or not accepted for For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and By the date listed in Part 1.

Overview Information , prospective applicants are asked to submit a letter of intent that includes the following information: Descriptive title of proposed activity Name(s), address(es), and telephone number(s) of the PD(s)/PI(s) Names of other key personnel Participating institution(s) Number and title of this funding opportunity The letter of intent should be sent to: Malcolm A.

Smith, MD, PhD All page limitations described in the SF424 Application Page Limits must be followed with the following modifications for this FOA. The Research Strategy must consist of the following sub-sections with the indicated page limits: Sub-section A. Overview of the Proposed PEP-CTN - 12 pages Sub-section B.

Clinical and Translational Research Program - Sub-section C.

Operations and Data/Statistics Center (ODSC) Instructions for Application Submission The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an All instructions in the SF424 (R&R) Application Guide SF424(R&R) Project/Performance Site Locations All instructions in the SF424 (R&R) Application Guide SF424(R&R) Other Project Information All instructions in the SF424 (R&R) Application Guide must be followed.

The following additional instructions apply. & Other Resources: In addition to standard documentation for this attachment, applicants must document the extent of their expertise in using MediData Rave and describe their implementation of protocols and usage of MediData Rave capabilities.

Applicants must also document their experience in using the NCI CTSU and OPEN for conducting protocols that enroll patients across multiple institutions. Applications that fail to document this experience will be considered incomplete.

Applicants must also document their capabilities for preparing and submitting Investigational New Drug Applications (INDs) in support of Network clinical trials and for meeting the regulatory responsibilities associated with being a study sponsor. Applications that fail to document these capabilities will be considered incomplete.

Attachments: Applicants must provide the following additional materials specified below in support of their application. Each attachment should be uploaded as a separate PDF using the indicated filenames (which will serve as application bookmarks). Brevity of the attached documentation is generally recommended.

1: Sample Protocol Template for Phase 1 Clinical Trials with a Phase 2 Expansion (use filename "Protocol template"). 2 : Procedures for Central Monitoring of Clinical Trials (use the filename "Central Monitoring").

Describe specific central monitoring procedure to include at a minimum source data verification of patients at each enrolling site [e.g., for informed consent, eligibility, first two courses of treatment (drug administration and AEs), and any other key data items] and tracking of source data verification (preferably through Medidata Rave), timeliness of data submissions and query resolutions, and factors that may trigger more frequent monitoring or on-site audits.

3 : Procedures for Member Institutional Performance Monitoring (use filename "Institutional Performance Monitoring").

Include Standard Procedures for periodically evaluating the performance of Core Member Institutions, addressing for example, such aspects accrual of adequate number of eligible patients to the PEP-CTN timely submission of required data; observance of clinical trial protocol requirements; contributions to clinical trial protocol development and conduct; authorship of PEP-CTN publications; participation in PEP-CTN administrative and scientific committees; and Other aspects deemed relevant.

Provide policies for handling unacceptable performance (for instance, use of warning letters, grace period to allow corrections); Provide a policy and mechanism for replacing institutions unresponsive to necessary correction action plans, including: Specific criteria (performance metrics) to identify the lower tertile of Core Member. Institutions (in terms of performance) and for competing these Network Core Member slots.

Provide procedure to re-compete the slots of the lower quartile of Core Member institutions, including criteria to be used in reviewing applications for membership. 4 : Proposed Conflict of Interest Policy for the PEP-CTN (use the filename "COI Policy).

This policy and associated procedures must be consistent with U.S. Public Health Service (PHS) requirements for ensuring that there is no reasonable expectation that the design, conduct, and/or reporting of research conducted by the proposed PEP-CTN will be biased by any conflicting financial conflict of interests of an investigator.

SF424(R&R) Senior/Key Person Profile All instructions in the SF424 (R&R) Application Guide All instructions in the SF424 (R&R) Application Guide It is expected that the budget requested for the PEP-CTN will be apportioned in approximately the manner described below. With the exception of specific instructions for funds that must be included by the applicant (see italicized text below), these estimates are informational. A.

Scientific Leadership (approximately 10% of direct costs Funded scientific leadership positions include the PD/PI (Chairperson of the PEP-CTN) and the PEP-CTN vice-Chair as well as the Genomics/Translational Biology, Pharmacokinetics, and Imaging scientific leaders. The effort level of the PEP-CTN Chairperson should be budgeted at a minimum of 1. 8 person-months.

This effort level cannot be reduced during the award period. study chairs totaling approximately $120,000 per year (based on $15,000 per chair for 8 active studies) but without providing specific individuals' names (i.e., use "To Be Determined") . B.

PEP-CTN ODSC (approximately 40-45% of direct costs Include support required for protocol development activities, data management activities, central monitoring and quality control/quality assurance activities, regulatory and human subjects' protections, communication with member institutions, and biostatistical support for data analysis and clinical trials development.

Include support for PEP-CTN meetings (two in-person network-wide Travel: expenses to support travel for one representative from each Member Site (up to 20 sites) and appropriate ODSC staff to travel to up to two in-person meetings per year. C. Funds for Member Institutions (approximately 35-40% of direct Reimbursement Fund.

For the purposes of budget preparation for per capita reimbursement, an annual accrual rate of 120 patients by Core Member Institutions should be assumed with average capitation payment of $5,000 (i.e., $600,000 per year). Assume an additional $200,000 per year to support enrollment from Phase 2 Expansion Institutions. List a total for the Per Capita Reimbursement Fund of $800,000 per year under the "Other Expenses" category.

Institutions Fund ($600,000 per year, independent of per capita reimbursement for patients enrolled in clinical trials) to support the non-accrual responsibilities associated with participating in the Consortium s clinical trials (e.g., site training, pharmacy set-up, and site administration) that must be met whether patients are ever enrolled on a study at an institution.

Include $600,000 for Core Member Institutions Fund under "Other Expenses" category.

Studies Research Funds ($100,000 per year) to be allocated 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 for pharmacokinetic studies, tumor tissue handling and shipping to the tissue bank or Biopathology Center, and performance of research imaging studies).

Include this fund in the "Other Expenses" category. D. Genomics/Translational/Pharmacokinetics Research Fund ($180,000 per year) to be used for laboratory studies (e.g., pharmacokinetic and pharmacodynamic studies and genomic studies) performed on specimens (e.g., blood, tumor tissue, buccal cells, etc.) obtained from children enrolled on PBTC clinical trials.

Include $180,000 per year for this Genomics/Translational/Pharmacokinetics Research Fund under "Other Expenses" category. E. Imaging Activities (approximately 5% of direct costs requested).

Use standard budget categories, as needed, for support of adequate post-acquisition image storage, processing, and analysis capabilities to support the Network's imaging objectives.

All instructions in the SF424 (R&R) Application Guide PHS 398 Cover Page Supplement All instructions in the SF424 (R&R) Application Guide All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions: Aims: Outline succinctly the overall strategic goals and overarching research strategy for the proposed PEP-CTN and the general organizational structure and plan to achieve these goals.

Research Strategy must consist of Sub-Sections A-D as A. Overview of the Proposed PEP-CTN. and Research Direction.

Outline the overall goals for the PEP-CTN and an overarching research strategy for the conduct of pediatric early phase trials Structure and Key Roles: Define the general organizational and governing structure, lines of authority and decision-making processes that you propose.

Explain how this organization and structure are designed to meet the needs of the Network in developing and implementing state-of-the-art clinical trials for children with cancer. Include plans for replacement of key leadership positions should leadership transitions be required.

Specific key roles to be described include, for example, the Network Chairperson and Vice-Chair, Lead Biostatistician and Leader of ODSC (if different), Imaging leader, Pharmacokinetics leader, and Genomics/Translational Biology leader. Indicate when one person will be leading more than one activity. Past Performance.

Summarize the past performance of the applicant team in the past 5-6 years in leading and managing multi-institutional pediatric early phase clinical trials. In this context, adult early phase clinical trials may also be mentioned, provided those adult clinical trials were directly applicable to the development and conduct of pediatric early phase clinical trials that are the focus of this FOA.

The description should deal with the team capabilities and cumulative accomplishments without repeating the information from individual