We propose a six point approach in order to improve access for adolescents to new anti-cancer drugs and to make the drug development process more efficient.
1. The age of clinical trial entry should be reduced to 12 years in adult early-phase anti-cancer drug studies that are relevant options in view of the adolescents’ unmet treatment needs, unless there are well-justifiable medical/scientific reasons not to do so. In practice, adolescent inclusion in adult trial should be considered where the MoA of the studied agent is potentially relevant to adolescents or when the disease is rarely present in adolescents. Enrolment for adolescents should commence when initial adult safety/PK data are available – this time point could be defined on a study by study basis (e.g. to enrol adolescents >12 years once the PK/safety data from the first 1-2 adult cohorts had been assessed in a dose-escalation Phase-I trial; or at the point of expansion adult cohorts opening). There should be PK/toxicity monitoring in the adolescents themselves. This would help ensure that adolescents are not exposed to potentially sub-therapeutic doses, and individual benefit would be a possibility.
2. There should be no set upper/lower age limit criteria for Phase-II and III trials for AYA cancers that are present in both paediatric/adult populations and have the same biology. Adolescents ≥12 years should be included from trial initiation. Additional adolescent PK/toxicity studies should be undertaken in Phase-II studies. The children <12 years should be included in the trial as soon as the paediatric RP2D is determined.
3. Trials enrolling adolescents should always be conducted in an age-appropriate setting with clinical care provided by expert paediatric or AYA oncologists, to ensure best safety, care and compliance. This could be facilitated by having co-principal investigators on studies, with separate responsibilities for adult and adolescent clinical care.
4. Adolescents should still be included in paediatric Phase-I, II and III trials where relevant (e.g. adolescents with paediatric cancers or paediatric targets), to maximise therapeutic opportunities.
5. Young adult patients should be permitted to participate in paediatric Phase-II/III trials, especially when their diagnosis is a ‘paediatric’ type cancer.
6. The indication proposed in a marketing authorisation application for a given anti-cancer drug should include adolescents at the same time as the adult authorisation. This should be possible based on including paediatric/adolescent data in the application, particularly where the disease crosses the age spectrum and has similar biological/clinical behaviour, and also, when diseases are histologically different but with similarly targets of the anti-cancer drug present across the age spectrum. Adolescent PK/safety data collected within the context of adult trials, even within trials for different diseases, might support extrapolation of activity between diseases. Such information should be included in the Summary of Product Characteristics. A joint paediatric/adult development strategy disease-adapted would accelerate adolescent access to new agents, whilst still assuring safety (by way of strict recommendations in the case of any encountered toxicity). Importantly, this would neither limit nor delay paediatric development for children <12 years, many of whom also have high unmet therapeutic needs in the relapsed/refractory disease setting.