Purpose: The current strategy of drug development has been criticized as being highly inefficient. In 2004, the US Food and Drug Administration (FDA) released recommendations to improve this process, including a push for increased use of enrichment trials. It is unclear to what extent aspects of this "Critical Path Initiative" have been adopted in trial designs in metastatic colorectal cancer.
Methods: A systematic review was conducted of actively enrolling treatment trials in metastatic colorectal cancer. Trials were identified from the National Cancer Institute's clinicaltrials.gov and Investigative Drug Branch databases. Trials were categorized based on the number of prior treatments allowed, phase of the trial, agent mechanism of action, and FDA approval status of agents under investigation.
Results: One hundred two trials are enrolling, with a combined enrollment goal of more than 20,000 patients. Thirteen percent of trials investigated an agent not yet FDA-approved for any oncology indication. The most common study design was a phase II study limited to previously untreated patients; compared with the remaining trials, these phase II trials were more than 10 times more likely to only use agents FDA-approved for colorectal cancer. Three percent of patients were enrolled onto trials enriched for tumor characteristics that were hypothesized to improve clinical benefit.
Conclusion: Current clinical trials for metastatic colorectal cancer are deficient in the investigation of agents directed at a novel therapeutic target, overuse phase II studies of FDA-approved agents, and fail to incorporate enrichment trial designs as encouraged by the FDA initiative.