Systematic survey of therapeutic trials for metastatic colorectal cancer: room for improvement in the critical pathway.
OBJECTIVE
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.


CONCLUSIONS
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.
Kopetz
Scott
S
Department of Gastrointestinal Medical Oncology, M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Box 426, Houston, TX 77030, USA. skopetz@mdanderson.org
Overman
Michael
M
Chang
David Z
DZ
Glover
Katrina Y
KY
Shureiqi
Imad
I
Wolff
Robert A
RA
Abbruzzese
James L
JL
Eng
Cathy
C
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic / Q000379:methods*; D017322:Clinical Trials, Phase II as Topic / Q000379:methods; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017277:Drug Approval; D006801:Humans; D009362:Neoplasm Metastasis; D014481:United States; D014486:United States Food and Drug Administration
D000970:Antineoplastic Agents