This fall, teams activated the , a phase 2 study that compares the effects of two chemotherapy regimens, FOLFIRINOX and FOLFOX, after long-course radiation therapy (RT) in patients with advanced stage rectal cancer. National Co-Principal Investigator (PI) of the study and lead MCW PI William Hall, MD, professor of Radiation Oncology and Surgery, and the research team hypothesize that using the FOLFIRINOX approach (a combination of drugs fluorouracil, irinotecan, leucovorin, and oxaliplatin) after RT will show superior clinical complete response (cCR) rates compared to FOLFOX.
“The JANUS trial significantly improves on past strategies for the treatment of rectal cancer,” said Dr. Hall. “The study is transformative because it allows patients to be managed with a “watch and wait” approach. In other words, we allow patients to undergo non-operative management. Because our primary endpoint is cCR (disappearance of the tumor on endoscopic and imaging evaluation), patients are not required to undergo surgery and can still be included for the primary endpoint.”
Dr. Hall noted that the addition of anti-cancer drug, irinotecan, to FOLFIRINOX could make the treatment more effective than FOLFOX, which combines fluorouracil, leucovorin, and oxaliplatin. “Irinotecan is a topoisomerase I inhibitor that works with other types of chemotherapy commonly used in patients with colon and rectal cancer,” he said.
Over the last year, Dr. Hall has co-authored several Journal of Clinical Oncology studies ( and , among others) that focused on the primary endpoints of clinical trials involving RT in gastrointestinal cancers. He explained that the JANUS trial represents a substantial change in rectal cancer management because it significantly modifies the primary endpoint from prior historic rectal cancer trials.
The study’s sponsor, Alliance for Clinical Trials in Oncology, expects to enroll 312 participants nationally. However, Dr. Hall explained that accruals have been exceeding expectations, and that the trial is in the process of revolutionizing the primary endpoints used for NCI-sponsored trials in rectal adenocarcinoma. “The trial may be converted to a phase 3, pending final NCI approval. This is very exciting, as it will represent a true standard of care-setting trial when it’s completed,” said Dr. Hall.