LAUSR

Background: Rare cancers occur with an incidence of no more than six cases per 100,000 people according to the definition used by the Surveillance of Rare Cancers in Europe project. For a variety of reasons (low prevalence, cytotoxicity), it is challenging to perform the necessary clinical studies to investigate the safety and efficacy of investigational medicines against such rare malignancies, reformulating even at the earliest stages of the drug development process. This article investigates the differences between phase I rare cancer trials performed in commercial (companies) and non-commercial settings (academic hospitals). Materials and Methods: The differences were explored through the conduct of semi-structured interviews with three different stakeholder groups: representatives from academia (n = 7), representatives from companies (n = 4) and representatives from patient organizations (n = 4). All the interviews were transcribed verbatim and analyzed in NVivo using the framework method. Results: According to the interviewees, the academic and commercial stakeholders collaborate in the majority of phase I rare cancer trials. In general, the commercial partner finances the trial, whereas academia is responsible for the execution of the study procedures. The average cost of undertaking these trials is difficult to estimate because it depends on what is specifically requested during the trial. The 3 + 3 study design remains the most widely used design and the use of expansion cohorts is controversial. With regard to the regulatory aspects of phase I rare cancer trials, it was expressed that a good regulatory framework facilitates the conduct of these studies, but that increased regulation and oversight also has drawbacks, e.g., differences in standards between different ethics committees, over interpretation of the rules, insufficient availability of qualified personnel and higher workloads. The patient organization representatives claimed that patients experience no differences in terms of accommodation, compensation and paperwork between the academic and commercial settings or the degree of follow-up. They also believed that the direct input of patients can bring added value to such studies not only with regard to the recruitment process and the feasibility of the study but also the legibility of the informed consent forms. Conclusion: The growing need for first-in-man trials in rare malignancies needs to be highlighted, as difficult as they are to undertake and to co-develop, not only because rare cancer patients deserve an appropriate treatment, but also because these medicines represent the future of cancer therapy in the precision medicine era. Cooperation of commercial and academic sites are needed. Patient organizations need to be educated to take part in this process.