Modernizing Clinical Trial Eligibility: Recommendations of the American Society of Clinical Oncology–Friends of Cancer Research Minimum Age Working Group

Abstract

Purpose Children have historically been excluded from first-in-human studies of promising new cancer drugs and later phase adult clinical trials. Delays in evaluation may result in off-label use without dosing information as the only access to new drugs. A multistakeholder workshop was convened in May 2016 by ASCO and Friends of Cancer Research to identify opportunities for when it would be scientifically appropriate to expand trial eligibility to include children younger than age 18 years in first-in-human and other adult cancer clinical trials. Methods This group convened experts from academia, government, and industry to review barriers to enrolling children and adolescents in oncology clinical trials. We evaluated the historical context, published literature, regulatory considerations, and myriad risks and benefits associated with lowering the age of enrollment on oncology clinical trials. Results We conclude that many of the historical concerns about including children early in oncology clinical trials do not apply in the current scientific and clinical environment of pediatric oncology and drug development; we provide specific recommendations for how the inclusion of children in early-phase investigational cancer drug trials might be accomplished. Automatic inclusion of pediatric patients is appropriate in early-phase trials that assess dose, safety, and pharmacokinetics in a variety of tumor types and later phase trials that assess efficacy in a specific disease that spans adult and pediatric populations. Conclusion Including children in appropriately designed adult clinical oncology trials is feasible and can be done in a way that enhances their access to these agents without compromising safety or development strategies.

Generalization and representativeness of phase III immune checkpoint blockade trials in non‐small cell lung cancer

“…However, when a study drug obtains FDA approval based on the results of sponsor-initiated trials, these patient populations also receive the drug. Inclusion of these 6,[29][30][31][32] Designing a trial that simultaneously enrolls both patients with restricted eligibility criteria and those defined by expanded eligibility criteria could be an alternative option. 28 Second, physicians should be cautious of interpretation and application of trial results to actual patients who are not well represented by the included study population.…”

Physician perspectives on compassionate use in pediatric oncology

“…According to the FDA, clinical trials are “the most efficient means to make safe and effective treatments available to the largest number of patients,” but exclusion criteria make it impossible for some patients to enroll. For children, age is one of the leading factors that make them ineligible . Pediatric compassionate use requests are often made for drugs that are being studied in adults, though the FDA or any other entity does not explicitly track the number of requests for children.…”

“…For children, age is one of the leading factors that make them ineligible. 22 Pediatric compassionate use requests are often made for drugs that are being studied in adults, though the FDA or any other entity does not explicitly track the number of requests for children.…”

Winning the RACE: Expanding pediatric cancer drug approvals

“…In parallel with the RACE act, there have been efforts to reduce the age of eligibility for adult trials from 18 to 12 years, expanding evaluation of new drugs into adolescents, a traditionally underrepresented group in clinical trials. There have been three publications as well as an FDA draft guidance recommending this decrease in initial age of eligibility …”

“…3,4 Similarly, the authors provide new data on timing of initial and pediatric drug approvals for the 21 anticancer agents granted pedi- three publications as well as an FDA draft guidance recommending this decrease in initial age of eligibility. [5][6][7] Even before formal implementation of these changes, we are seeing a move toward age-agnostic development strategies. Barone and colleagues highlight the simultaneous adult and pediatric development and approval of chimeric antigen receptor T-cells targeting CD19 (tisagenlecleucel) for relapsed/refractory B-cell acute lymphoblastic leukemia.…”