Notice Number: NOT-CA-17-021
Key Dates
Release Date: January 25, 2017
RFA-CA-16-501
Issued by
National Cancer Institute (NCI)
Purpose
This Notice is to inform the scientific community that the National Cancer Institute (NCI) is modifying RFA-CA-16-501, "Cancer Immunotherapy Trials Network (CITN)(UM1)" to now include a significant element for clinical trials in immunotherapy for pediatric patients.
The following Sections of RFA-CA-16-501 are revised accordingly:
Part 1: Overview Information
Section 1. Funding Opportunity Purpose
Currently reads:
The purpose of this limited Funding Opportunity Announcement (FOA) is to support the infrastructure to design and conduct multi-institutional Phase I and early Phase II clinical immunotherapy trials for cancer patients, using novel immunomodulatory agents. To realize these goals, the FOA will continue to support the research activities of the Cancer Immunotherapy Trials Network (CITN).
The CITN to be supported through this FOA will consist of:
- The Central Operations and Statistical Office (COSC), which will provide overall leadership, organizational infrastructure, and statistical coordination support for the CITN; and
- Clinical Member Sites (up to 25 institutions) as sites that will conduct the clinical trials, supported through subcontracts within the CITN award.
Modified to read:
The purpose of this limited Funding Opportunity Announcement (FOA) is to support the infrastructure to design and conduct multi-institutional Phase I and early Phase II clinical immunotherapy trials for adult and pediatric cancer patients, using novel immunomodulatory agents.To realize these goals, the FOA will continue to support the research activities of the Cancer Immunotherapy Trials Network (CITN).
The CITN to be supported through this FOA will consist of:
- The Central Operations and Statistical Office (COSC), which will provide overall leadership, organizational infrastructure, and statistical coordination support for the CITN; and
- Clinical Member Sites (up to 25 institutions) as sites which will conduct the clinical trials foradult patients (and for pediatric patients as appropriate), supported through subcontracts within the CITN award, with up to five additional sites devoted exclusively to enrolling pediatric patients.
Part 2. Full Text of Announcement
Section I. Funding Opportunity Description
Purpose
Currently reads:
The purpose of this limited funding Opportunity Announcement (FOA) is to continue to support the research activities of the Cancer Immunotherapy Trials Network (CITN), specifically to design and conduct multi-institutional Phase I and early Phase II clinical immunotherapy trials for cancer patients using novel immunomodulatory agents.
The CITN to be supported through this FOA will consist of:
- The Central Operations and Statistical Office (COSC), which will provide overall leadership, organizational infrastructure, and statistical coordination support for the CITN; and
- Clinical Member Sites (up to 25 institutions) as sites that will conduct the clinical trials, supported through subcontracts within the CITN award.
Modified to read:
The purpose of this limited Funding Opportunity Announcement (FOA) is to continue to support the research activities of the Cancer Immunotherapy Trials Network (CITN), specifically to design and conduct multi-institutional Phase I and early Phase II clinical immunotherapy trials for pediatric and adult cancer patients using novel immunomodulatory agents.
The CITN to be supported through this FOA will consist of:
- The Central Operations and Statistical Office (COSC), which will provide overall leadership, organizational infrastructure, and statistical coordination support for the CITN; and
- Clinical Member Sites (up to 25 institutions) as sites which will conduct the clinical trials for adult patients (and pediatric patients as appropriate) supported through subcontracts within the CITN award, with up to five additional sites devoted exclusively to enrolling pediatric patients.
Other Changes to Funding Opportunity Description are added at the end of the Background section.
Background
Additional Background section:
Although immunotherapeutic approaches to childhood cancer have been successfully introduced for selected cancers, with sustained complete responses in children with refractory leukemia using an anti-CD19 chimeric antigen receptor engineered (CAR) T cell approach and with improvement in survival for children with high-risk neuroblastoma using an anti-GD2 chimeric monoclonal antibody strategy, for most patients with high-risk or refractory childhood cancers there is no effective immunotherapeutic option. The addition of a pediatric element to the CITN is part of multi-component effort by NCI to accelerate the pace at which further effective immunotherapies are realized for childhood cancers. It is likely that the development of successful pediatric immunotherapy will require a distinctive focus when compared to immunotherapy for adult cancers. While less focus on checkpoint inhibitors and related approaches designed to enhance the immune response to tumors with high neoantigen content resulting from high tumor mutation burden is likely, increased focus on approaches designed at targeting the immune system towards aberrantly expressed embryonal antigens using CAR T cells, bispecific T cell engaging antibodies, antibody-drug conjugates, and other approaches is needed. A pediatric arm of the CITN will be well placed to both recognize these research opportunities and to then expeditiously translate them into clinical testing with the requisite laboratory correlates to obtain optimum information on the effects of the treatment.
In order to address the need for inclusion of pediatric immunotherapy trials, the overall scientific scope of the CITN will include therapies of specific relevance to children and adolescents with cancer, such as for instance relevant cellular therapies and antibody-based therapies (including antibody-drug conjugates) and targeting surface antigens preferentially expressed on childhood cancers. It is expected that three to four trials per year that focus on children and adolescents with cancer, in addition to the three to four trials in adult cancers, for a total of 30-40 trials, will be implemented. For conducting pediatric trials, Member Sites selected for adult trials that have pediatric immunotherapy expertise may be included in a pediatric subgroup of the CITN, with up to 5 additional sites enrolling only pediatric patients. Pediatric-only sites that are added to the CITN should show the capability of contributing to the scientific leadership of the network and show evidence of successfully participating in pediatric early phase clinical trials, including pediatric immunotherapy clinical trials, with careful monitoring of patients and timely reporting of data. Further, both the Executive and Steering Committees should include both adult and pediatric leadership, with formation of a separate Steering committee for the design and oversight of the Pediatric Immunotherapy trials. (see changes to Cooperative Agreement Terms and Conditions for details)
Section II. Award Information
Funds Available and Anticipated Number of Awards
Currently Reads:
NIH intends to fund one award, corresponding to a total of approximately $2.0 million, for fiscal year 2017.
Modified to read:
NIH intends to fund one award, corresponding to a total of approximately $4.0 million, for fiscal year 2017.
Award Budget
Currently reads:
The applicant may request a budget of up to $1,500,000 annually in direct costs.
Modified to read:
The applicant may request a budget of up to $3,000,000 annually in direct costs.
Section IV. Application and Submission Information
2. Content and Form of Application Submission
: R&R Budget
Currently reads:
A. COSC (allocate approximately $600,000 per year)
- Scientific Leadership: Funds allocated for the PD/PI designated to be in charge of the overall scientific direction of the CITN and head of the COSC. An additional leader of the COSC (a designated potential substitute PD/PI) may be identified (this individual could be a PD/PI under the multiple PDs/PIs framework) and receive support. Funds required for biostatistical support staff for data analysis and clinical trials development and monitoring should also be included. The effort level of a PD/PI designated to be in charge of the overall scientific direction of the CITN and head of the COSC should be budgeted at a minimum of 1.8 person-months. This effort level cannot be reduced during the award period.
- Administrative and regulatory support: Funds for communication activities with Member Sites and with CTEP for protocol development and implementation (include protocol coordinators, administrative staff, regulatory and human subjects' protections personnel, finance staff.
- Network meetings: Funds to support one to two in-person network-wide and Steering Committee meetings and teleconference calls for protocol team and Executive and Steering Committee meetings.
- Travel: expenses to support travel for one representative from each Member Site (up to 25 sites) and appropriate COSC staff to travel to up to two in-person meetings per year (Steering Committee and network-wide investigator meetings).
B. Per-Patient Reimbursements to Member Sites (allocate approximately $900,000)
- The sub-contractual arrangements for Member Sites selected should include funding (calculated on a per protocol basis) for managing the clinical trial at the particular Member Site and for the laboratory components selected, specifically, for specimen collection and transfer to immune monitoring laboratory associated with the CITN.
- Per-patient reimbursement costs (including specimen collection costs) to be allocated to participating Member Sites should be budgeted at the rate of $7,000 per patient. Since approximately 120 patients/year are projected, these costs allocated to all Member Sites are projected to not exceed $900,000 annually.
Modified to read:
A. COSC (allocate approximately $1,200,000 direct costs per year)
- Scientific Leadership: Funds allocated for the PD/PI designated to be in charge of the overall scientific direction of the CITN and head of the COSC. An additional leader of the COSC (a designated potential substitute PD/PI) may be identified (this individual could be a PD/PI under the multiple PDs/PIs framework) and receive support. The leader of the pediatric element of the CITN should receive support (CITN Pediatric Leader). Funds required for biostatistical support staff for data analysis and clinical trials development and monitoring should also be included. The effort level of a PD/PI designated to be in charge of the overall scientific direction of the CITN and head of the COSC should be budgeted at a minimum of 1.8 person-months, as should the effort level of the CITN Pediatric Leader. This effort level cannot be reduced during the award period.
- Administrative and regulatory support: Funds for communication activities with Member Sites and with CTEP for protocol development and implementation (include protocol coordinators, administrative staff, regulatory and human subjects' protections personnel, finance staff), for both adult and pediatric activities.
- Network meetings: Funds to support one to two in-person network-wide and Steering Committee meetings and teleconference calls for protocol team and Executive and Steering Committee meetings.
- Travel: expenses to support travel for one adult and one pediatric representative (when applicable) from each Member Site (up to 30 sites) and appropriate COSC staff to travel to up to two in-person meetings per year (Steering Committee and network-wide investigator meetings).
B. Per-Patient Reimbursements to Member Sites (allocate approximately $1,800,000 direct costs per year)
- The sub-contractual arrangements for Member Sites selected should include funding (calculated on a per protocol basis) for managing the clinical trial at the particular Member Site and for the laboratory components selected, specifically, for specimen collection and transfer to immune monitoring laboratory associated with the CITN.
- The Per-patient reimbursement costs (including specimen collection costs) to be allocated to participating Member Sites should be budgeted at the rate of $7,000 per patient. Since approximately 250 patients/year are projected, these costs allocated to all Member Sites are projected to not exceed $1,800,000 annually.
PHS 398 Research Plan
Sub-section: A. CITN Overview
Additional CITN Overview section
For the Research Plan overview, include a separate section that specifically addresses the overall goals of the CITN and research strategy for early phase trials as this applies to pediatric immunotherapy trials; specifically address how pediatric immunotherapy researchers will be incorporated into the general organizational and governing structure, including how the COSC will interact with the pediatric clinical sites; and, how the CITN pediatric leadership will interact with the PD/PI (in concert with the Pediatric Steering Committee) to drive the scientific direction in the pediatric immunotherapy arena. For the description of the COSC, include how the COSC will incorporate the development and implementation of pediatric immunotherapy trials in their overall work scope and standard procedures. For the Research Program, include a listing with justification of high priority agents for pediatric trials expected for study, and a description of overall plans including several concepts expected for further trial development, including any combination approaches; include any plans for immunomonitoring if considered specific for pediatric trials analyses. For Member Sites, list both the adult and pediatric leader if a Member Site will include both Pediatric and Adult components, as well as any new Pediatric-specific Member sites.
Section VI: Award Administration Information:
: 2. Administrative and National Policy Requirements
Cooperative Agreement Terms and Conditions of Award
Areas of Joint Responsibility include:
Currently reads:
The CITN will have a Steering Committee as a governing body. The Steering Committee will include the following voting members:
- PD/PI (or PD/PIs, if this option is used)
- One representative from each Member Site (site Clinical Leader or designated investigator);
- The Lead Statistician at the COSC;
- A patient advocate; and
- NCI Project Scientist(s) and Program Official
Modified to read:
The CITN will have both an Adult and a Pediatric Steering Committee as governing bodies. The Steering Committees will include the following voting members:
- PD/PI (or PD/PIs, if this option is used) for the Adult Steering Committee
- The Pediatric CITN Leader for the Pediatric Steering Committee
- One representative from each Member Site (site Clinical Leader or designated investigator for pediatric or adult clinical trials as appropriate);
- The Lead Statistician at the COSC;
- A patient advocate (with both a pediatric and an adult patient advocate for their respective committees;) and
- NCI Project Scientist(s) and Program Official
Currently reads:
The CITN liaison to the appropriate Immunomonitoring Core laboratory and lead statistician will participate in Steering Committee meetings but will not be voting members.
Modified to read:
The CITN liaison to the appropriate Immunomonitoring Core laboratory (with separate persons for adult and pediatrics) and lead statistician will participate in Steering Committee meetings but will not be voting members.
Currently reads:
The Steering Committee will be chaired by a Member Site Clinical Leader, elected by the members after nomination by the Executive Committee. The Chair-elect and past chair will also sit on the Steering Committee.
Modified to read:
The Steering Committee for adult clinical trials will be chaired by a Member Site Clinical Leader, elected by the members after nomination by the Executive Committee. The Chair-elect and past chair will also sit on the Steering Committee. The Steering Committee for pediatric clinical trials will be led by the CITN Pediatric Steering Committee Chair and co-Chair (chair-elect).
Currently reads:
Executive Committee (EC). This committee will be composed of: the CITN PD/PI, (or PDs/PIs, if multiple PD/PI option is used), the Steering Committee chair, the chair-elect, the past-chair, senior administrator, the lead statistician as well as a senior administrator from the Operations/Statistical office, a liaison to the appropriate Immunomonitoring Core, and the NCI Program Officers (Program Director and Project Scientist).
Modified to read:
Executive Committee (EC). This committee will be composed of: the CITN PD/PI, (or PDs/PIs, if multiple PD/PI option is used), the Pediatric CITN Leader, the Adult Steering Committee chair and co-chair (chair-elect), the Pediatric Steering Committee Chair and co-Chair (chair-elect), senior administrator, the lead statistician as well as a senior administrator from the Operations/Statistical office, a liaison to the appropriate Immunomonitoring Core (with separate persons for adult and pediatrics) and the NCI Program Officers (Program Director and Project Scientist(s)).
All other aspects of RFA-CA-16-501 remain unchanged.
Inquiries
Please direct all inquiries to:
William D. Merritt, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-6137
Email: merrittw@mail.nih.gov
and Human Services (HHS)
