Case studies of adaptive early phase trials

Published on December 29, 2016   44 min

Other Talks in the Series: Adaptive Clinical Trial Design

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My name is Daniel Normolle, and I am the Director of Biostatistics at the University of Pittsburgh Cancer Institute. I'm going to be discussing three case studies of adaptive early phase clinical trials today.
The first trial involves the use of gemcitabine, oxaliplatin, and radiation therapy in pancreatic cancer. This is a dose-escalation trial of oxaliplatin. The second trial is an example of stereotactic beam radiotherapy for intrahepatic cancer using an assay to predict radiation-induced liver disease. And the third trial will be a discussion of fish oil as a colon cancer chemopreventitive.
These are the topics I'm going to address in the first trial. Basically, this is a TITE-CRM trial, and we're going to look at first the scientific background of the use of oxaliplatin along with gemcitabine and radiation therapy. I'm going to talk about the operating characteristics of the TITE-CRM trial. Why we chose it. How it gets implemented, and the results.
So in the vast majority of patients, pancreatic cancer remains incurable. It's a fatal disease. Even patients with potentially curative resection may benefit from chemoradiotherapy. When this trial was conceived in 2003, radiation treatment of 54 Gy over six weeks with concurrent gemcitabine was the standard at the University of Michigan. However, oxaliplatin, approved by the FDA in 2002, was of great interest. The recommended phase 2 dose of oxaliplatin, when administered concurrently with radiation therapy and gemcitabine, was to be determined.
We were going to test six levels of this treatment. Level -1 was a fallback level we did not intend to visit. We were going to escalate oxaliplatin. And if oxaliplatin was successfully escalated to 85 mg/m2, we would then increase the dose of gemcitabine. The levels are not scaled but they are ordered in terms of intensity.