Enrolling Adolescents in Disease/Target-Appropriate Adult Oncology Clinical Trials of Investigational Agents

Abstract

The enrollment of adolescents with cancer in clinical trials is much lower than younger pediatric patients. For adolescents with “adult-type” cancers, lack of access to relevant trials is cited as one of the reasons for this discrepancy. Adolescents are generally not eligible for enrollment on adult oncology trials, and initial pediatric trials for many drugs are conducted years later, often after the drug is approved. As a result, accrual of adolescents to these trials may be slow due to off-label use, prospectively collected safety and efficacy data is lacking at the time of initial approval, and, most importantly, these adolescents have delayed access to effective therapies. In order to facilitate earlier access to investigational and approved drugs for adolescent patients with cancer, and because drug exposure is most often similar in adolescents and adults, we recommend the inclusion of adolescents (ages 12-17) on disease and target-appropriate adult oncology trials. This approach requires careful monitoring for any differential safety signals, appropriate pharmacokinetic evaluations, and ensuring that ethical requirements are met. Inclusion of adolescents on adult oncology trials will require the cooperation of investigators, cooperative groups, industry, IRBs, and regulatory agencies to overcome real and perceived barriers.

Role of clinical trials in survival progress of American adolescents and young adults with cancer—and lack thereof

“…The U.S. Food and Drug Administration (FDA) has recently encouraged the inclusion of 12–17 year olds on disease‐ and target‐appropriate adult oncology trials . An FDA Advisory Committee for Pharmaceutical Science and Clinical Pharmacology reviewed this age group in 2012 and recommended that adolescent (>12 years) patients be enrolled on trials for adult patients without the need for a previously dedicated pharmacokinetic study in them, a recommendation that has not been enacted.…”

Enhancing accrual to clinical trials of adolescents and young adults with cancer

“…Consequently, the major funder of cancer research in the UK asks all new investigators to scientifically justify age eligibility criteria, and unless scientifically sound the lower age must be 16 years rather than 18 . The US Food and Drug Administration (FDA) recently acknowledged the underrepresentation of adolescents in adult studies and the impact of conducting paediatric trials later and often after approval of the new agent . Consequences include slow recruitment to the paediatric trial due to off‐label use resulting in a lack of prospectively collected safety and efficacy data in adolescents.…”

“…The FDA has advocated lowering the age eligibility criteria similar to the UK. However, they go further to suggest that adult studies should include adolescents aged 12–17 years where the tumour is similar or the drug targets or molecular rearrangements are relevant . In support of this drug exposure in AYA, patients have shown to be similar (readers are referred to the FDA paper for the dosing strategies of adolescents in adult trials) .…”

Bridging Adult Experience to Pediatrics in Oncology Drug Development

“…Logistical issues include different geographic locations/institutions involved in the care of adolescents and separate institutional review boards; these may be overcome by centralized institutional review boards and increased collaboration among clinical trial networks and pediatric and adult oncologists. 41 A perceived regulatory barrier may be additional preclinical studies, although juvenile animal studies are not always mandated prior to first-in-pediatric evaluation of oncology drugs. 42 Inclusion of adolescents in adult oncology clinical trials represents a paradigm shift from pediatric oncology drug development that follows adult drug development, often after drug approval.…”

“…42 Inclusion of adolescents in adult oncology clinical trials represents a paradigm shift from pediatric oncology drug development that follows adult drug development, often after drug approval. 41 …”