publication date: Jul. 2, 2020

NCI BSA approves nine new and reissue concepts

By Alexandria Carolan

The NCI Board of Scientific Advisors has approved nine new and reissue concepts—Request for Applications, Cooperative Agreement, Request for Proposals, and Program Announcements with special receipt, referral and review.

The presentations are available here.

The following concepts were approved at the June 15 meeting of the BSA.


New Cohorts to Assess Environmental Exposures and Cancer Risk (RFA)

The purpose of this RFA is to support new cancer etiology cohorts that use innovative

strategies and approaches to:

  • Address knowledge gaps between environmental exposures, genetics, and other molecular factors and cancer etiology across diverse populations,

  • Ensure rigor and reproducibility of data and biospecimen collections.

The goal is to fund approximately five new cohorts to:

  • Assess new and understudied exposures with innovative designs and measures,

  • Focus on both short-term and longer-term research questions,

  • Facilitate investigator collaboration—by Coordinating Center,

  • Create common data elements and biospecimen collection,

  • Prioritize innovative, significant, and actionable research.

This RFA is in response to NCI NCAB Cohort Subcommittee Report (2019) that emphasizes needs for new etiology cohorts to address research gaps on exposures. The total cost for five cohorts is $63 million over six years.

This RFA was submitted by the Division of Cancer Control and Population Sciences. The RFA will receive funding through the UG3/UH3 grants. The UG3 phase PI sets milestones for recruitment and data collection (requires approval from Program and NCI leadership), and the UH3 phase is focused on completing research.

The evaluation criteria are based on:

  • Innovation: Priority to innovative and novel projects and study designs using technological and molecular innovation to address identified research gaps related to environmental exposures,

  • Inclusivity: Representation of understudied and diverse populations,

  • Strong scientific justification for research questions to be addressed, approach, and population; willingness to collect core data and biospecimens,

  • UG3/UH3 milestones must be appropriate,

  • Data sharing—compliance with NIH policies; and

  • Proposals for the CC will be evaluated on the evidence of having provided administrative and logistic support for cohorts.


Childhood Cancer Survivorship Study (CCSS) (Re–issue RFA)

The Childhood Cancer Survivorship Study is a retrospectively ascertained cohort with ongoing, longitudinal follow-up of survivors of pediatric and adolescent cancer diagnosed between 1970-1999; 21 years old, English or Spanish speaking; leukemia, lymphoma, CNS, Wilms, NBL, soft-tissue and bone sarcoma.

CCSS includes:

  • 37,593 eligible five-year survivors (evaluable for late mortality studies); 25,664 participants; 14,361 (diagnosed 1970-86); 11,303 (1987-99); 5,059 sibling controls,

  • Open resource data collection for each participant includes: detailed treatment including RT organ-based dosimetry; biospecimens—germline DNA; SMN somatic tissue,

  • Self-reported health/psychosocial outcomes and risk factors collected at baseline and on six longitudinal follow-up surveys,

  • 367 publications >700 Investigators, 80 trainees,

  • 54 investigator-initiated studies; $53.1 million grant support.

This reissue RFA was submitted by the Division of Cancer Treatment and Diagnosis, and is co-sponsored by the Division of Cancer Control and Population Sciences, Division of Cancer Epidemiology and Genetics and Division of Cancer Prevention.

The estimated cost is $2.74 million/year for a total of $13.7 million in direct costs over five years. The funding grant was not specified.

New opportunities for the CCSS include:

  • Evaluating physiologic/neurocognitive aging and underlying mechanism of accelerated aging in the cohort (and compared to siblings) using in-home direct assessment of a subset of survivors,

  • Enhancing the resource to better facilitate conduct of health services research,

  • Facilitating studies utilizing genomic data from cohort, and expanding capability for data sharing for collaboration with other cohorts,

  • Promoting precision prevention by developing clinical risk prediction tools,

  • Establishing a cloud-based data sharing platform that would make all CCSS data, both clinical and genomic, readily available to all investigators,

  • Expanding intervention studies portfolio including using mHealth approaches,

  • Initiating the CCSS Vanguard Cohort: a process of identification, enrollment, and follow-up of survivors diagnosed 2000-2020 who received novel therapies as part of standard therapy or protocols, for future expansion of the CCSS resource.


Clinical Trials Monitoring Service (CTMS) (RFP)

The purpose of the Clinical Trials Monitoring Service is to provide infrastructure and core services for data management, quality assurance, and monitoring for the Experimental Therapeutics Clinical Trials Network and other early-phase clinical trials, including limited support of the National Cancer Trials Network, and other projects.

CTMS ensures protection of human subjects, collection of high quality clinical data, and

compliance with HHS, NCI, FDA, and Good Clinical Practice requirements.

This RFP was submitted by the Division of Cancer Treatment and Diagnosis. The cost of the contract over 10 years is $88.8 million.

Contract options are:

  • Option C: Funding to conduct up to three Good Manufacturing Practice audits per year,

  • Option D: Funding to conduct up to five Good Laboratory Practice audits per year,

  • Option E: Funding for major IT to support any immediate needs related to specific regulatory, legislative or IT system change,

  • Option F: Implementation of an electronic informed consent.

Task I of CTMS is a centralized patient registration system, protocol patient data capture resource using Medidata Rave, and a systematic process for data quality control reviews for ETCTN studies and other early phase clinical trials. The first task of CTMS provides coordination of a Data Safety Monitoring Board for randomized ETCTN studies. CTMS also displays key data items in Web Reporting for IDB Medical Officer review and oversight for all ETCTN and NCTN studies conducted under Cancer Therapy Evaluation Program held IND.

Task II of CTMS is to provide on-site auditing to assure clinical investigations are conducted in compliance with federal regulations, NIH/NCI policies, guidelines, and procedures and process for verification of data via source data review.

Task III of CTMS includes co-site visitation of NCTN Network Group audits primarily focusing on sites with past performance issues.

Task IV of CTMS is to conduct audits at cancer centers and other institutions (non-NCTN) participating in Division of Cancer Treatment and Diagnosis-sponsored clinical trials, to assure that trials are in compliance with protocol and regulatory requirements and NIH/NCI policies and procedures.


Collaborative Approaches to Engineer Biology for Cancer Applications (RFA/Coop. Agr.)

The purpose of this RFA/Coop. Agr. is to promote innovative synthetic biology approaches to challenges across cancer research through engineer and cancer researcher partnerships.

The overall goal of the RFA/Coop. Agr. is to:

  • Stimulate collaborations between engineers and cancer researchers to expand use of synthetic biology to advance understanding and management of cancer,

  • Bring more engineers and novel approaches and technologies to cancer research,

  • Drive technology application through cancer research.

Example research directions (technology and cancer research advancement) are:

  • In situ recording of exposures and genetic changes in pre-cancer and cancer,

  • Sensitive, minimally invasive biosensors to amplify signals and/or report levels of cancer-related biomarkers,

  • Targeted, controlled therapeutic delivery or therapeutic action using engineered mammalian cells or microbes.

This RFA/Coop. Agr. was submitted by the Office of the Director. The project collaborates with the National Institute of Biomedical Imaging and Bioengineering. The total cost through the U01 grant is $4.2 million for year one, which includes $3.2 million from NCI and $1 million from NIBIB. This RFA/Coop. Agr. includes funding for four to six awards.

This RFA/Coop. Agr builds on NIBIB and other NIH investment, including:

  • NIH Synthetic Biology Consortium annual meeting

    • Cancer challenges amenable to synthetic biology approaches,

    • More bridges across communities.

  • 25 funded NIBIB grants that:

    • Provide technology development, variety of biological systems (limited cancer),

    • Establish projects primed for cancer application.

Successful applications will address the significance of the cancer research question and potential of technology, provide expertise in engineering, cancer, and mathematical modeling, be technology feasibility, and include an application in mammalian tissue or model system.

Program successes include new collaborations, publications, presentations, patents, grants, research resources—including models, protocols, controllable cellular components, and trained fellows and early-career investigators.


The NCI Predoctoral to Postdoctoral Fellow Transition Award (F99/K00) (Reissue RFA)

The goal of the NCI predoctoral to postdoctoral fellow transition award is to show that a cancer research career is rewarding, valuable, and viable, to identify the best and brightest and engage and retain them in the cancer research community.

The award, submitted by the Office of the Director, also helps cancer researchers join top laboratories of their choice in oncology, and positions trainees for a K99/R00 award. The reissue concept’s total cost per cohort is $11 million, with 24 awards per year and one receipt date per year for five years.

The award was established five years ago.

The 6-year-award was created to address the mismatch between the number of trainees and independent investigator positions. There’s been a doubling of students receiving doctorates in biomedicine over the last 30 years, and a tripling of postdoctorates—but the number of investigator positions has not increased.

The F99/K00 Predoctoral to Postdoctoral Fellow Transition award:

  • Includes one application per institution per year,

  • Provides support for up to two years of predoctoral work and up to four years of postdoctoral training (up to six years),

  • Has K00 salary levels that exceed current National Research Service Award stipends,

  • Is portable and allows flexibility in selecting postdoctoral training opportunities.

The applicant receives the award as a graduate student during the F99 stage (pre-doc phase). Review criteria include:

  • Quality of applicant, academic and publication record,

  • Recommendation letters,

  • Brief update on accomplishments,

  • Description of research leading to degree,

  • Mentor to hold R01-equivalent grant.

At the transition point, the applicant comes back with a brief proposal for the F99-K00 transition (Postdoc Phase). The proposal includes:

  • Proposed mentor’s support,

  • Short research description for postdoc training.

The mentor must hold an R01-equivalent grant. Approval is granted at discretion of the NCI program director.


Small Business Transition Grant (RFA)

The purpose of the Small Business Transition grant is an entrepreneurial grant that’s modeled after the k99/R00.

Junior scientists are transitioning to entrepreneurship, and there’s not a transition grant to help them make this leap. There are some restrictions—a K99 to small business grant doesn’t exist. NCI has created a STTR/SBIR hybrid that will accomplish the same goals as the K99/R00.

This RFA, submitted by the Office of the Director, is a 2-year pilot with five to seven awards per year.

Phase I of the STTR:

  • Requires collaboration with university,

  • PI primary employment not stipulated (min.10% effort to project),

  • $400,000 / 12 months.

Phase II of SBIR:

  • Permits collaboration with university,

  • PI primary employment MUST be with the SBC for the duration of the project period,

  • $2 million / two years.


Phase I of STTR:

Training:

  • SBC PI: Postdoc,

  • Mentoring plan required,

    • Technical mentor,

    • Business mentor,

Technical:

  • PI preps technology to move to SBC,

  • I-Corps at NIH require.


Transition to Phase II of SBIR:

  • Personnel,

    • PI moves to SBC,

  • Tech update,

    • R&D milestones,

    • Commercialization plan,

    • IP agreement.


Phase II SBIR:

  • Training;

    • Same PI (non-transferrable),

    • Mentoring continues,

      • Contact type and frequency in mentoring plan.

  • Technical

    • Most research conducted at SBC site,

    • Small pivots allowed,

    • No major scope changes.

Eligibility criteria stipulate that recipients must be a maximum of eight years from a terminal degree. Women and scientists from underrepresented racial and ethnic groups are encouraged to apply.

Mentoring special review criteria are:

  • Working with NCI CCT to learn from K99/R00,

  • Technical mentor commitment: cannot mentor more than one entrepreneur simultaneously,

  • Business mentor: can utilize mentoring programs, but must identify a lead mentor,

  • Expect the mentors to commit to a minimum of 2 hours/week and I-Corps at NIH (Phase I).

Technology development is a critical component of this RFA. The application must include milestones and go/no-go criteria for fast-track transition. NCI is not guaranteeing training support to grantees whose technology fails.

The RFA includes a request for NCI-run peer review:

  • NCI would like to issue this as a pilot RFA with set-aside funds,

  • Commercialization expertise on panels is also important for special review criteria,

  • This is a new mechanism and concept, which will work closely with NCI DEA during the pilot,

  • Form review criteria with help of NCI CCT program directors with K99/R00 experience.


The Cancer Genome Atlas Network: TCGA Genome Characterization (GCCs) and TCGA Genome Data Analysis (GDACs) Centers (Reissue RFA/Coop. Agr.)

The goal of the TCGA Project is to develop and function as an integrated research network. Due to the TCGA success, all future CCG-approved genomics projects will utilize a similar model.

Here are some lessons learned from TCGA:

  • Need of high quality molecular analytes,

  • Experiments performed utilizing strict standardized protocols,

  • Deposit the results in structured formats in publicly accessible databases.

This reissue RFA/Coop. Agr. was submitted by the Office of the Director. All awards are expected to be U24 Cooperative Agreements, with a total of $25,000 over five years.

The proposed analytical network will serve to understand the data generated by CCG programs as well as collaborations with other divisions:

  • The Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trials (ALCHEMIST),

  • Exceptional Responders (ER, in collaboration with DCTD),

  • Clinical Trials Sequencing Program (CTSP, in collaboration with DCTD)

  • Carcinomas of Unknown Primary (CUPP),

  • Refractory Cancers (Peripheral T-cell lymphomas, recurrent GBMs).

This resource can be utilized by any NCI project that uses the characterization pipeline developed for TCGA and now available as a set of contracts.

The whole network will be made up of specialized cores that will address the following competencies:

  • Coding and non-coding mutations,

  • Expression/mRNA analysis,

  • Copy number/purity analysis,

  • miRNA analysis,

  • Long non-coding RNA analysis,

  • Batch effects/integration,

  • Methylation analysis,

  • Pathway analysis,

  • Single-cell sequencing analysis,

  • Analysis of circulating cell-free DNA (cfDNA) and circulating tumor DNA (ctDNA),

  • Long-read sequencing analysis,

  • Special genomics analysis,

  • Digital imaging analysis.


PAR Reissue Concepts

The following PAR reissue concepts were submitted by the Office of the Director. There was no associated budget presented with any of the concepts.

  • Modular R01s in Cancer Control and Population Sciences. Funding: R01 grant. Awarded grants: Five for PAR-18-869.

  • Secondary analysis and integration of existing data to elucidate the genetic architecture of cancer risk and related outcomes. Funding: R01, R21. Awarded grants: Seven for PA-17-239, five for PA-17-243.

  • Cancer Prevention and Control Clinical Trials Grants Program (R01-Clinical Trials Required). Funding: R01 grant. Awarded grants: 76 for PAR-18-559.

  • Specialized Programs of Research Excellence (SPOREs) in Human Cancer for Years 2021 through 2023. Funding: P50 grant. Awarded grants: 17 for PAR-18-313.

  • Innovative Research in Cancer Nanotechnology. Funding: R01 grant. Awarded grants: 12 for PAR-17-240.

  • Investigator-Initiated Early Phase Clinical Trials for the Division of Cancer Treatment and Diagnosis Programs. Funding: R01. Awarded grants: 40 for PAR-18-560.

  • Assay development and screening for discovery of chemical probes, drugs or immunomodulators. Funding: R01 grant. Awarded grants: 35 for PAR-17-438.

  • Academic-Industrial Partnerships for Translation of Technologies for Cancer Diagnosis and Treatment. Funding: R01 grant. Awarded grants: 12 PAR-18-530.

  • Revision Applications for Validation of Biomarker Assays Developed Through NIH-Supported Research Grants. Funding: P01, P50, R01, U01, U10, UH2/UH3 grants. Awarded grants: 0 for PAR-20-074.

  • The NCI Transition Career Development Award. Funding: K22 grant. Awarded grants: One for PAR-18-466, 14 for PAR-18-467.

  • Cancer Research Education Grants Program (R25). Funding: R25 grant. Awarded grants: Four for PAR-18-476, 10 for PAR-18-477, 10 for PAR-18-478.

  • Exploratory Grant Award to Promote Workforce Diversity in Basic Cancer Research (R21 Clinical Trial Not Allowed). Funding: R21 grant. Awarded grants: Eight for PAR-18-731.

  • Research Specialist Award. Funding: R50 grant. Awarded grants: 0 for PAR-19-290 and PAR-19-291.


Clinical Translation of Activated Optical Fluorescence Methods and Technologies for Sensitive Cancer Detection In Vivo (PAR)

The purpose of this Moonshot PAR is to demonstrate enhanced sensitivity of imaging that will enable physicians to locate small tumors indicated by fluid-based diagnostic results, and

and to do this within the framework of the Moonshot program.

The PAR’s goal is to enhance clinically focused study of activated fluorescence to demonstrate tumor imaging sensitivity in line with fluid based biopsy results.

The PAR, submitted by the Office of the Director, will receive funding through the R01 grant. There was no associated budget presented for this concept.

Greater imaging sensitivity is important because it can provide early detection, anatomic staging and treatment planning, detection of residual disease or metastatic disease, and reduced patient anxiety.

Novel devices are needed to reduce noise in the system, creasing resolving power, and provide a sufficient field of view. Increasing contrast of the image can increase sensitivity without requiring costly hardware improvements.

The PAR:

  • Seeks teams with track record in activated fluorescence research for in vivo imaging

    • Development challenges mostly solved.

  • Emphasizes the need for a team approach

    • Clinical input and imaging input both required,

    • Technical complexity can be overcome.

  • Requires clinical trial validation

    • Preclinical research excluded: Toxicity will not be studied in this program.

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