Joint adolescent–adult clinical trials proposed
medwireNews: In a bid to improve access to novel drugs for adolescent patients with cancer, the ACCELERATE working group has suggested including adolescents aged 12–17 years in early-phase adult clinical trials.
Nathalie Gaspar, from Gustave Roussy Cancer Campus in Villejuif, France, and fellow ACCELERATE colleagues emphasize that such inclusions would only be permitted if there were no medical or scientific contraindications, and only if the drug’s mechanism of action was potentially relevant to adolescents or if the tumor type was rare in the adolescent population.
They believe, however, that this approach is a “more efficient alternative compared with the current unsatisfactory situation.” Specifically, the authors explain that adolescents are generally bracketed with pediatric patients in the present drug development landscape, which can delay their access to novel anti-cancer agents that are already available for adults. In some cases, adolescent trials are opened, but the rarity of the condition leads to low accrual and subsequent early closure.
“Both situations have inadvertently lead to off label drug use in adolescents, with no data collected, delaying adolescent data collection for marketing authorisation,” they write in the Annals of Oncology.
Therefore, the multi-stakeholder ACCELERATE group sought to address the issue by conducting a literature review and initiating discussions between representatives of all interested parties, including academics, patient and parent advocacy groups, regulatory agencies, and pharmaceutical companies, to arrive by consensus at the proposed approach.
The authors note that the proposal is supported by “similar dosing and [pharmacokinetic] parameters in adolescents and adults.” Also, the evidence to date suggests similar acute toxicity profiles as well, with no additional toxicities seen in adolescents, they say.
Gaspar et al highlight factors that they believe will be crucial for the successful implementation of joint adolescent–adult clinical trials. For instance, the timing of recruitment, which “should be balanced between opening to adolescents once there is some adult safety and [pharmacokinetic] data, but not so late that few can realistically participate,” the authors write.
They continue: “This will avoid […]adolescents being exposed to potentially sub-therapeutic doses, and maximise the chance for individual benefit, complying with the requirement that paediatric/adolescent patients participating in research have the prospect of direct benefit which justifies the risk of participation.”
Other key factors include the optimal dosing for adolescents, which can be based on the adult dose as adjusted by body surface area, and identifying the number of adolescents to be recruited, which should be part of the upfront overall enrolment calculation.
Noting that such joint trials may benefit not just adolescent access to drugs, but also adult drug development, the authors conclude: “[O]ur proposed strategy has very recently been endorsed by the FDA, further demonstrating the progressive international harmonisation of views on this key issue.”
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