(Fast-Track proposals will be accepted.)
Number of anticipated awards: 3–5
Budget (total costs):
Phase I: $250,000 for 9 months;
Phase II: $1,500,000 for 2 years
It is strongly suggested that proposals adhere to the above budget amounts and project periods. Proposals with budgets exceeding the above amounts and project periods may not be funded.
The deadline for receipt of all contract proposals submitted in response to this solicitation has expired/ It was: November 13, 2012 by 5 p.m. EST.
Radiotherapy is employed in the treatment of over half of all cancer patients. Many of those patients suffer adverse effects during and/or after treatment. Additionally, tumors recur in approximately half the patients treated with curative intent. Enhancing specific tumor killing and minimizing normal tissue damage from radiotherapy would improve tumor control and patient quality of life. An ideal intervention would both enhance radiation effects in tumors and protect the normal tissues.
Radiosensitizers are agents that are intended to enhance tumor cell killing while having a minimal effect on normal tissues. Recently, two new radiation sensitization drugs have proven clinically effective: Temozolomide treatment with radiotherapy for glioblastoma and Cetuximab treatment combined with radiation for head and neck squamous cell cancers. There is significant potential for further development of novel radiosensitizing agents.
Conventionally, radioprotectors are defined as agents given before radiation exposure to prevent or reduce damage to normal tissues, while mitigators refer to those agents given during or after a patient's prescribed course of radiation therapy to prevent or reduce imminent damage to normal tissues. Both radioprotectors and mitigators are also being developed as potential countermeasures against radiological terrorism and several have shown promise in pre-clinical testing. In order for these to be developed and useful in clinical radiation therapy applications, it is imperative to demonstrate that they do not protect cancer cells.
The importance of developing agents that sensitize tumor cells, protect or mitigate radiation-induced damage in normal tissue, improve survival, quality of life, and palliative care in cancer patients was emphasized in a recent NCI workshop on Advanced Radiation Therapeutics – Radiation Injury Mitigation held on January 25th 2010 (Movsas B, et al. Decreasing the adverse effects of cancer therapy: National Cancer Institute guidance for the clinical development of radiation injury mitigators. Clin Cancer Res. 2011 Jan 15;17(2):222-8. Epub 2010 Nov 3. PMID: 21047979), and in a workshop on Radiation Resistance in Cancer Therapy: Its Molecular Bases and Role of the Microenvironment on its Expression held Sept 1–3, 2010. Prior workshops have dealt with sensitization, protection, or radiation effects assessment (Colevas AD, et al. Radiation Modifier Working Group of the National Cancer Institute. Development of investigational radiation modifiers. J Natl Cancer Inst. 2003 May 7;95(9):646-51. Review. PMID:12734315; Stone HB, et al. Models for evaluating agents intended for the prophylaxis, mitigation and treatment of radiation injuries. Report of an NCI Workshop, December 3–4, 2003. Radiat Res. 2004 Dec;162(6):711-28. PMID: 1554812.)
This contract topic encourages the development of innovative and promising radioprotectants, mitigators, or sensitizers that either selectively protect normal tissues (but not tumors) against ionizing radiation or selectively sensitize tumors, thereby increasing the therapeutic ratio of radiation. Proposals for radiation modulators are solicited that include preclinical and/or early phase clinical studies demonstrating safety, efficacy, dose, schedule, pharmacokinetics (PK), pharmacodynamics (PD), and metabolism. Proposals should also demonstrate a clear understanding of regulatory requirements, and should include a regulatory plan including key steps such as a pre-IND meeting with FDA, submission of an investigational new drug (IND) application, approval of clinical trial design, and ultimately drug registration.
The goal is to stimulate collaborations among academic institutions, small businesses, and contract research organizations in order to promote the rapid development of innovative radioresponse modifiers that will decrease normal tissue injury and/or enhance tumor killing thereby improving radiotherapy outcomes. The long-term goal is to enable small businesses to fully develop, license, and/or market radioresponse modifiers for clinical use.
Phase I may include primarily preclinical studies. Phase II or "Fast-Track" proposals must contain a section entitled "Regulatory Plan" detailing plans for early involvement of the FDA. There should be a description of how the applicant plans on meeting the requirements to: 1) define suitable biomarkers and endpoints, 2) file IND and 3) design and perform phase 0-2 clinical trials in preparation for product transition to phase 3 clinical trials by groups such as the Radiation Therapy Oncology Group.
Where cooperation of other partners is critical for implementation of the proposed methodology, the applicant should provide evidence of such cooperation (through partnering arrangement, letters of support, etc.).
The following deliverables may be required depending on a compound's maturity in the developmental pipeline:
For advanced pre-clinical work:
For proposals advancing to early phase human trials: