NIH – Early Phase Clinical Trials in Imaging and Image-Guided Interventions (R01)

February 20, 2017 by School of Medicine Webmaster

The goal of this re-issued FOA is to promote and accelerate clinical evaluation of imaging modalities, agents, methods, and image-guided interventions to improve cancer management. Therefore, projects that propose Phase I or early Phase II studies of imaging agents and methodologies, or feasibility studies of imaging devices, image-guided surgery or therapies, image-guided radiation therapy using external beams and/or systemic radionuclides, should show that the anticipated preliminary data will be able to justify a future grant application for confirmatory Phase II or Phase III trial. A range of trials at different stages of development are allowed, including first in human Phase I and II single-site or multi-site studies based on conventional or adaptive trial designs (if economically feasible). The early studies should provide important initial information regarding imaging investigations (e.g. safety, tolerability, dosing). Later-stage studies should yield data that allow clear go/no-go decisions regarding whether these imaging investigations or image-guided interventions should proceed to an efficacy trial. Applicants may, for example, propose to conduct a clinical trial where the primary aim is to:

  • Evaluate and optimize the dose, safety, tolerability or pharmacokinetics of an imaging agent or intervention in a target population.
  • Produce sufficient evidence of short-term activity (e.g., imaging biomarker activity, pharmacodynamic response, target engagement, dose-response trends) in a human proof of concept trial.
  • Select or rank the best of two or more potential imaging interventions, technologies, or dosing regimens to be evaluated in a subsequent trial, based on tolerability, safety data, biological activity, or preliminary clinical efficacy (e.g., a futility trial.)
  • Conduct exploratory IND studies with less preclinical toxicity data or less micro-dosing of investigational agents than usually required for traditional first in human studies to improve the trial design and efficiency in subsequent trials. See FDA’s website for information regarding FDA’s Exploratory IND Guidance document.

If proven successful, these investigations can then be validated in larger studies through competitive R01 FOAs, or through clinical trials in the Specialized Programs of Research Excellence (SPOREs), Cancer Centers, and/or the NCI’s National Clinical Trials Network program.

Areas of General Interest

This FOA is applicable to a broad range of clinical imaging evaluations associated with or without therapeutic endpoints. For example, the testing of imaging biomarkers can be in the context of distinguishing aggressive from indolent tumors/disease or selecting appropriate risk adaptive therapies (e.g., image-guided radiation therapy using external beams and/or systemic radionuclides) or risk stratification. Projects in any area of technology development that advance cancer-related imaging science through clinical trials are welcome provided sufficient pre-clinical evidence has been established to validate use in clinical studies. Examples of appropriate scientific interests under this FOA include, but are not limited to the assessment of: imaging methods and agents including but not limited to  PET, SPECT, MR, US and optical imaging (biodistribution, pharmacokinetics, tracer kinetic modeling, etc.), nanocomponent devices and formulations for imaging  (theranostic agents) imaging systems and devices (advances in multi-modality instrumentation, etc.), advanced image processing and analysis techniques (radiomics, etc.) to improve cancer care. Opportunities where the proposed imaging agents and technologies can be explored in the context of NCI’s high priority targets in cancer research (e.g. signaling pathways, tumor biology, etc.) or linked to developments stemming from NCI’s current programs (e.g. NCI Experimental Therapeutics Clinical Trials Network, Cancer Imaging Program’s Quantitative Imaging Network, NCI Experimental Therapeutics (NeXT), and NCI Alliance for Nanotechnology in Cancer) are also encouraged.

Molecular and functional imaging, as well as image-guided interventions that help address health issues and disparities in underserved populations, are encouraged for this FOA. Examples of issues that can be examined include, but are not limited to, novel imaging or image-guided approaches to evaluate differences in safety and efficacy of imaging agents and monitoring of differences in response to therapy among different racial and ethnic populations.

Specific Features

This FOA supports research projects in which prospective clinical trials are proposed where novel or advanced clinical imaging and IGI investigations are feasible. Extensive preliminary data are not required. Since “innovation” – as defined in this FOA’s context – includes investigations of novel or advanced imaging and/or IGI methods in early phase clinical trials, the proposed research should seek to challenge existing paradigms or offer the possibility of new or improved methods for diagnosis, intervention, and response evaluation for example.  This includes projects that by their nature are not highly innovative but essential to advance the field.

Applications submitted under this FOA should address the following to ensure proper peer review and better assure completion of the proposed clinical trial in 2-3 years.

  • A full and complete clinical protocol must be developed before submission.
  • The proposed imaging or IGI solutions should be  ready for use in human subjects in their application.  This means that pre-clinical safety and tolerability must be established before one can apply.
  • There should be a plan as to how the targeted accrual will be achieved within the project period.
  • Applicants are encouraged to apply for an Investigational New Drug (IND) approval or Investigational Device Exemption (IDE), as necessary, prior to or at the time of submission to show that the proposed trial can start promptly upon award.

Deadlines:  June 28, 2017; October 11, 2017; February 14, 2018, June 28, 2018; October 11, 2018; February 14, 2019; June 28, 2019; October 11, 2019; February 14, 2020 (letters of intent are due 30 days before the deadline for full proposals)


Filed Under: Funding Opportunities