Implementing Criteria to Expand Clinical Trial Eligibility

An Analysis of NCI Cancer Therapy Evaluation Program (CTEP)-Sponsored Protocols

Guidelines for clinical trial eligibility are important to provide safety for patients and ensure that the study population is well characterized, but excessively narrow criteria can be an impediment to progress in the development of cancer therapeutics. Narrow eligibility criteria can exclude too many people, leading to study results that may not inform treatment options for the diverse groups of people with a particular cancer. Therefore, it is important for investigators to carefully consider whether each eligibility criterion in a clinical trial is too narrow and would unnecessarily exclude people.

A 2017 joint statement from the American Society of Clinical Oncology (ASCO) and Friends of Cancer Research (Friends) outlined recommendations from four working groups to expand and modernize clinical trial eligibility. These working groups provided recommendations and protocol template language to expand eligibility for the following criteria:

• brain metastases
• age < 18
• HIV infection
• prior and concurrent malignancies and organ dysfunction, including cardiac, liver, and kidney function

Implementation of the Expanded Eligibility Recommendations

CTEP provided updated template language to principal investigators to implement the proposed expanded criteria into their clinical trial protocols. We evaluated compliance with implementation of the new broadened criteria and language in CTEP-approved protocols from November 1, 2018 through April 30. The analysis included 122 trials (71% early and 29% late phase), and 84% were studies with INDs with industry collaborators. We presented the results of this analysis in a poster at the 2021 ASCO Annual Meeting.

Summary of Study Results

• Compliance with the new criteria language ranged from a high of 87.7% of the protocols for liver function to a low of 37.2% of the protocols for new or progressive brain metastases.
• New criteria language was lacking in nearly 46% of trials for the concurrent or prior malignancy criteria and 31% of trials for the cardiac criteria.
• Of the 86 trials for non-localized disease or non-brain tumors, 47.7% did not address brain metastases, leaving it to investigator discretion. Thus, 62.8% of trials could theoretically enroll patients with brain metastases.

Conclusions and Next Steps

Maximizing opportunities for diverse populations to participate in trials is a priority for NCI; therefore, CTEP is using the findings from our study to continue to improve the protocol development and review process to ensure broader eligibility in clinical trials.

• Many protocols in our analysis included the broadened template language, but some added restrictive language without a clear rationale. If a protocol review finds that an investigator has added limitations to the expanded criteria, then CTEP will require that the investigators provide the scientific rationale.
• CTEP will incorporate the new 2021 ASCO/Friends recommendations in our protocol template to further expand eligibility criteria in the areas of performance status, prior therapies allowed, concomitant medications, washout periods, and testing intervals (Kim, 2021).

The era of precision oncology increases the potential for limitations in clinical trial participation due to molecular profiling of participants’ tumors. Therefore, eligibility criteria must be as broad as safely possible to achieve diverse and representative populations in future clinical trials. CTEP will continue to collaborate with investigators and industry partners in our shared responsibility to expand eligibility and access to trials.