Request for Information (RFI): Input on a Combination of Targeted Radionuclide Therapy (TRT) with Other Cancer Treatment Modalities

Notice Number: NOT-CA-19-025

Key Dates
Release Date : February 25, 2019
Response Date: by April 15, 2019

Related Announcements
None

Issued by
National Cancer Institute (NCI)

Purpose

The goal of this Request for Information (RFI), issued by the National Cancer Institute (NCI), is to gain feedback, comments, and novel ideas from members of cancer research communities with regard to possible combination of targeted radionuclide therapy (TRT) with other cancer treatment modalities. Specifically, opinions are sought on the relevant data that are already available, the knowledge gaps, the new studies that would enable such combinations, and the infrastructure required to carry out the necessary research. The information gained through this RFI will be used by the NCI’s Radiation Research Program (RRP), Cancer Imaging Program (CIP) and Cancer Therapy Evaluation Program (CTEP) to assess the current status and the need of research activities required to facilitate a broad application of TRT in combination with the current standard of care.

Background

TRT involves the precise delivery of radioactive isotopes to specific molecular targets. TRT uses passively targeted radionuclides as well as radiopharmaceuticals which have radionuclides attached to molecular targeting agents, such as antibodies, proteins, peptides, or small molecules. Radioactive isotopes used in TRT can emit several forms of ionizing radiation including alpha (helium nuclei) or beta (electrons) particles, Auger or conversion electrons, all of which have a relatively short range of tissue penetration, facilitating delivery of radiation doses to cancer cells while relatively sparing nearby normal cells.  Replacing therapeutic radionuclides with those used for imaging, a theranostic approach can potentially facilitate improved prediction and monitoring of therapeutic response, and optimization of treatment planning.

The recent approvals of 223RaCl2 (Xofigo) and 177Lu-DOTATATE (Lutathera) for the treatment of patients with, respectively, bone metastases from castration-resistant prostate cancer and somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors, respectively, have reinvigorated interest in TRT.

This RFI is being published to gauge the interest in the U.S. nuclear medicine, radiation oncology, medical oncology, medical physics, and radiation biology communities to investigate, through extensive pre-clinical and clinical research, possible combination therapies and strategies incorporating TRT for cancer treatment.

Information Requested
All stakeholders with an interest in cancer therapy are invited to provide information on the feasibility of TRT combination with other cancer treatment modalities and the data needed to validate such combinations in pre-clinical models and clinical trials, essential for FDA-approved use in clinical practice. The responses are entirely voluntary and may be anonymous.

NCI is seeking information that includes, but is not limited to, the following areas:

  • Plausible combination with targeted and cytotoxic agents, immunotherapy, and external radiotherapy;
  • Methodology required to determine starting dosages of radionuclide and drugs for combination therapies;
  • The relevant data that are already available;
  • Relative biological effect (RBE) of the particles emitted from radiopharmaceuticals;
  • The negative or positive effects of combination therapies;
  • Methodology to evaluate toxicity and pharmacology of combination therapies;
  • Likely regulatory requirements;
  • Barriers to implementation;
  • Types of research required to facilitate such combinations;
  • Types of resources needed and what existing resources can be utilized/repurposed and/or
  • Any additional issues relevant to this RFI that are not specifically mentioned above.

How to Submit a Response
Responses to the RFI will be accepted until April 15, 2019. All comments must be submitted by email to: capalaj@mail.nih.gov.

No proprietary, classified, confidential, or sensitive information should be included in responses.
Responses will be compiled and shared internally within the NCI and/or with working groups convened by the NCI, as appropriate. The compiled information may also appear in public reports and may inform the development of a research-support initiative(s) at an undetermined time in the future.

We look forward to your input. We also hope that you will share this document with your colleagues.

Important Note: This RFI is for planning purposes only and should not be construed as a solicitation or as an obligation on the part of the Federal Government and the NCI. The NCI does not intend to make any research awards on the basis of responses to this RFI or to otherwise pay for the preparation of any information submitted, or for the Government's use of such information.

Inquiries

Please direct all inquiries to:

Jacek Capala, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-5690
Email: capalaj@mail.nih.gov