CHARIOT: Our first dose escalation trial using the Time to Event Continual Reassessment Method – Design, Difficulties, Delivery
Frangou E., Holmes J., Love S., Hawkins M.
CHARIOT is a single-arm open-label, phase I dose escalation trial and is the first trial examining the combination of radiotherapy, chemotherapy, and the ataxia telangiectasia mutated Rad3-related (ATR) inhibitor M6620 in patients with oesophageal cancer. The aim is to identify the maximum tolerated schedule associated with no more than a predefined target toxicity level (TTL). CHARIOT consists of three stages, each with a different TTL. CHARIOT is the first trial in our grant-funded clinical trials unit using a time to event continual reassessment method (TiTE-CRM). The TiTE-CRM has changed the scene for radiotherapy trials where toxicity follow-up is often 3-6 months as it accommodates these late onset toxicities of radiotherapy as patients do not need to be fully observed to the end of the toxicity period before recruiting the next patient. Until this time, we had been unable to convince clinicians to use a model based design. We demonstrate how we managed to get clinicians and trial management staff on board and promote the use of Bayesian trials. From designing the trial, applying for and securing funding to set-up, we describe how we engaged the clinical trial team and funders, solving many practical issues in the use of the TiTE-CRM.