FDA finalizes guidance on including patients with incurable cancers in oncology trials

Regulatory NewsRegulatory News
| 29 July 2022 | By Jeff Craven 

The US Food and Drug Administration (FDA) has issued final guidance on the inclusion of patients with incurable cancers in clinical trials for investigational therapies.
In their guidance, the agency recommended sponsors include patients with incurable cancer—defined as unresectable, locally advanced, or metastatic disease in solid tumors and/or hematologic malignancies with unfavorable long-term overall survival—in oncology clinical trials even if they met criteria that would otherwise exclude them, such as in situations where a patient had previously received an available therapy in a non-curative setting. The recommendation by FDA emphasizes that sponsors still need to follow regulations around informed consent before enrolling patients with incurable cancer in clinical trials.
During the release of the draft guidance in June 2021, Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, said the guidance is part of a broader initiative by the agency to encourage enrollment of patients with incurable cancers in clinical trials. (RELATED: FDA calls for inclusion of patients with incurable cancers in oncology trials, Regulatory Focus 24 June 2021)
“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should be eligible to participate in oncology clinical trials,” Pazdur said in a statement released alongside the draft guidance. “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.”
Previously, the FDA has sought to include older patients in clinical trials and premenopausal women in breast cancer drug trials; they have also released final guidance documents on extending eligibility in cancer clinical trials to patients with brain metastases, hepatitis B or C virus, HIV infection, and organ dysfunction, or prior or concurrent malignancies. (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)
Safety evaluations in early-stage dose escalation studies
Comments made in response to the draft guidance were largely positive, with stakeholders praising the expanded eligibility recommendation, while other comments took issue with drawing a distinction between curative and non-curative therapies. (RELATED: Groups suggest changes to FDA’s guidance expanding eligibility criteria for oncology trials, Regulatory Focus 27 August 2021)
The agency said in its Federal Register notice announcing the final guidance that it had made one change from the draft guidance, which was to add a recommendation for safety evaluations in early-stage dose escalation studies.
In their comment responding to the draft guidance, Bristol-Myers Squibb proposed FDA include a recommendation to allow evaluating safety evaluations in Phase 1 dose-escalation studies for patients even if they have a heterogenous prior therapy history.
“The small size of dose escalation cohorts renders subgroup analysis impractical. The ability to evaluate dosing in heterogeneous groups of patients (defined by prior receipt of available therapy) together, would allow sponsors to more easily adopt the expanded patient eligibility criteria into earlier stages of development,” the company wrote. “The safety profile among patient sub-groups that differ in their exposure to certain prior available therapy(ies) can be confirmed to be the same in larger follow-up studies.”
FDA’s final guidance now states evaluating safety in early-dose escalation studies may be reasonable “without stratifying for prior receipt of available therapy(ies), if the potential toxicities of the investigational oncology product are not expected to differ across these patient subgroups.”
Cancer Clinical Trial Eligibility Criteria: Available Therapy in Non-Curative Settings


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