Design and analysis of early phase adaptive platform trials in the era of precision oncology Institute of Cancer Research in United Kingdom

BackgroundWe need efficient, innovative and robust early phase I/II trial designs to swiftly test new cancer therapies and ensure safe and effective ones are being progressed to later stage trials. Recent advances in precision oncology (which aims to match cancer treatments to the patient’s unique form of cancer) have motivated innovative trial designs, particularly the idea of master protocol (e.g., basket, umbrella and platform trial), for the evaluation of molecularly targeted cancer therapies. Early phase adaptive platform trials (EP-APTs) are such innovative approaches and indisputably can provide efficiency improvements, statistically or operationally or both: (a) statistically - allowing within-trial information sharing of safety and preliminary efficacy data (and hence increase in precision or power); (b) operationally - evaluating several targeted therapies for one (or more) diseases concurrently, and accepting additions of new treatment arms or patient population during the trial[1]. EP-APTs often also incorporate pre-specified changes (adaptations) to trial aspects to be made by analysing interim data. Such adaptations include early stopping of treatment arm(s) as soon as enough evidence is gathered or allocating more patients to treatments showing greater benefits.[2,3]  What the studentship will encompass: The student will be based within ICR-Clinical Trials and Statistics Unit (ICR CTSU) and work closely with the Drug Development Unit where they will benefit from real-life experience working with specialists on early phase cancer clinical trials. The objectives of this project are to:(a)      Review existing literature of the design and analysis approaches of early phase platform trials in precision medicine. (b)      Develop new approaches motivated by ongoing and published early phase adaptive platform trials addressing methodological issues, such as intra-patient dose-escalation strategies (gradually increasing a drug’s dose for the same patient), reliable short-term outcomes, joint evaluation of safety and efficacy, response-adaptive randomisation, and pooling of information across arms using Bayesian techniques.(c)       Test the statistical properties of selected trial designs and analysis strategies.(d)      Implement newly developed efficient methodologies in ongoing clinical trials or influence the methods used in future trials.Expected outputs: At least 3 peer reviewed publications are anticipated in methodological/clinical trial journals. Detail of supervisionThe supervisory team includes early phase expert methodologists (Christina Yap, Ken Cheung and Xiaoran Lai) and clinicians from the ICR/Royal Marsden Drug Development Unit (Juanita Lopez and Johann de Bono).Detail of any planned field work/ Secondments/industry placementA research visit to Columbia University (US) to work with Prof Cheung and his methodology group can be planned as part of the studentship. Such visit will provide the student an invaluable opportunity to work with international leading adaptive design specialists. Detail of any PPIThe project will include consulting patient and public partners on their views of the novel features of such adaptive platform trials and the additional efficiencies they offer. The student will also be encouraged to co-develop simple ways to explain complex methods to lay audience. See Alger et al. 2024 as an example[4].