Speaker
Description
The use of combination treatments in early phase oncology trials is growing. The objective of these trials is to search for the maximum tolerated dose combination from a pre-defined set. However, cases in which the initial set of combinations does not contain one close to the target toxicity level pose a significant challenge. There is uncertainty around how to handle these situations effectively in practice and the literature does not fully evaluate potential solutions.
To address this, we propose a novel method for inserting dose levels mid-trial. The idea is based on evaluating contours that partition the set of combinations into ones above and below the target toxicity. Dose insertions are made only if a single contour is highly probable, indicating an absence of combinations to explore around the target toxicity.
We examine our proposed approach applied to two established designs, although any model-based or model-assisted design is an appropriate candidate. Results from our comprehensive simulation study demonstrate that the insertion method can increase the probability of selecting combinations close to the target toxicity, whilst controlling for selecting overly toxic combinations. These methods can be extended to more complex settings, such as trials with joint toxicity and efficacy endpoints.
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