FDA calls for inclusion of patients with incurable cancers in oncology trials

Regulatory NewsRegulatory News
| 24 June 2021 | By Michael Mezher 

Patients with incurable cancers should be included in clinical trials for investigational cancer therapies, regardless of whether they have received available treatments, the US Food and Drug Administration (FDA) recommends in a draft guidance released Thursday.
“The FDA believes patients with incurable cancers, if provided adequate information to make an informed decision, should be eligible to participate in oncology clinical trials. If there is no scientific rationale for excluding these patients, then clinical trial eligibility criteria should be broadened to include these patients, with appropriate informed consent,” said Richard Pazdur, director of FDA’s Oncology Center of Excellence.
The draft guidance follows other recent moves by the agency to broaden inclusion in oncology clinical trials. (RELATED: FDA encourages inclusion of older patients cancer trials, Regulatory Focus 9 March 2020; FDA finalizes guidance on broader cancer trial eligibility, Regulatory Focus 10 July 2020; FDA 'may require' post-marketing studies to analyze long-term effects of breast cancer drugs, Regulatory Focus 21 June 2021).
FDA explains that its regulations require it to determine that subjects “are not exposed to an unreasonable and significant risk of illness or injury … to allow such trials to proceed.” Thus, eligibility criteria should generally require that patients have received available therapy(ies) that offer the potential for a cure. Or, in the case of trials with an add-on design, available therapy should be administered to all participants.
However, these criteria can oftentimes cause patients with incurable cancers to be excluded from enrolling in clinical trials.
“The draft guidance is intended to facilitate increased clinical trial options for patients with non-curable cancers by recognizing that, with appropriate informed consent, it maybe reasonable for patients to be eligible for inclusion in trials of investigational cancer drugs, regardless of whether they have received available therapy, in the non-curative setting,” FDA writes.
FDA explains that for the purposes of the guidance, “non-curative” is defined as “circumstances where there is extremely low likelihood for sure or for prolonged and/or near normal survival with available therapies.” The agency provides some examples of specific examples of cancers it considers non-curative, including “hematologic malignancies or solid tumors that are unresectable, locally advanced, or metastatic cancer with unfavorable long-term overall survival.”
The brief, two-page, draft guidance provides two recommendations for cancer trial sponsors.
First, sponsors are encouraged to expand eligibility criteria so that patients may be eligible for inclusion in trials of investigational drugs, including first-in-human trials, with appropriate informed consent, “regardless of whether they have received available therapy in the non-curative setting.” The informed consent should include all elements required under 21 CFR part 50.25 and “should clearly state that other treatment options known to confer clinical benefit exist, and should include a discussion of possible benefits, risks and uncertainties associated with the drug.”
Second, FDA recommends that sponsors evaluate patients who have received available therapy(ies) and those who have not in separate cohorts, “particularly if interpretation of efficacy results requires a homogenous patient population.” FDA also offers sponsors the alternative of conducting efficacy analyses using pre-specified subgroup analyses, with subgroups defined by prior receipt of available treatment.
FDA, Draft Guidance, Federal Register Notice


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