FDA Recommends Including Patients on Trials Regardless of Prior Therapies in the Non-Curative Setting

In a draft guidance for clinical investigators and sponsors, the FDA made recommendations on how to expand eligibility to patients with incurable cancer through clinical trial designs of investigational cancer drugs and biological products with the document “Cancer Clinical Trial Eligibility Criteria: Available Therapy in Non-Curative Settings.”¹

“…The FDA issued a draft guidance encouraging industry to include patients with incurable cancers—when there is no potential for cure or for prolonged/near normal survival—in cancer clinical trials, regardless of whether they have received existing alternative treatment options,” 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 in a statement. “Historically, many clinical trials have required that participating patients previously received multiple therapies.”

Once finalized, the recommendations in the draft guidance will help sponsors and investigators include more patients who have not received available the therapy or therapies in the non-curative setting. In this guidance, non-curative is defined as either unresectable, locally advanced, or metastatic disease in solid tumors, or hematologic malignancies with unfavorable long-term overall survival.²

However, patients who are eligible for available therapies that could potentially cure their disease, such as in pediatric acute lymphoblastic leukemia, testicular cancer, or classic Hodgkin’s lymphoma, should receive those treatments before being eligible for a clinical trial. If they do not receive these therapies before an investigational cancer treatment, they may be exposed to unreasonable or significant risk of illness or injury.

“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 press release.¹ “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.”

This FDA guidance states that patients who have not received the available therapies in the non-curative setting could be eligible for inclusion on first-in-human trials and beyond through the expansion of the eligibility criteria and the appropriate informed consent.² Consent includes “a disclosure of appropriate alternative procedures or courses of treatment, if any, that might be advantageous to the subject,” according to FDA standards. This informed consent must clearly state that other treatment options that offer clinical benefit are available and also include a discussion of potential risks, benefits, and uncertainties associated with the study drug.

Additionally, the FDA recommends evaluating patients who have not received the available therapies in separate cohorts from patients who were already given the available treatments in their setting. This is especially recommended for trials where the efficacy results need to be interpreted in a homogenous patient population. This separation could also be done using pre-specified subgroup analyses that have been defined before patients receive the trial drug or treatment.

“This draft guidance is part of the FDA’s broader initiative to encourage rational expanded patient eligibility for oncology clinical trials,” Pazdur concluded.

_References:

_{1. FDA in brief: FDA encourages inclusion of patients with incurable cancer in oncology clinical trials regardless of prior therapies. FDA. Published June 24, 2021. Accessed July 12, 2021. https://bit.ly/2T66OSh}

_{2. Cancer clinical trial eligibility criteria: available therapy in non-curative settings. FDA. Published June 24, 2021. Accessed July 13, 2021. https://bit.ly/3efHccZ}