Dr Hall on the Rationale of the Janus Rectal Cancer Trial

“This [study] is going to answer an absolutely fundamental and unknown question: What is the best type of chemotherapy that should be given in the neoadjuvant setting?”

William A. Hall, MD, a professor in and the chair of radiation oncology, the medical director of Froedtert Radiation Oncology, and the Bob Uecker Endowed Chair, Department of Surgery, School of Graduate Studies, at the Medical College of Wisconsin, discussed the clinical rationale for the phase 2/3 Janus Rectal Cancer Trial (NCT05610163).

During the 2026 Gastrointestinal Cancers Symposium (ASCO GI), Hall presented the design of the Janus Rectal Clinical Trial. Patients were randomly assigned 1:1 to receive FOLFOX (leucovorin, fluorouracil, and oxaliplatin), with bevacizumab (Avastin) or cetuximab (Erbitux)/CAPOX (capecitabine and oxaliplatin) or modified NALIRIFOX (irinotecan liposome [Onivyde], oxaliplatin, 5-fluorouracil [5-FU], and leucovorin) and FOLFIRINOX (leucovorin, 5-FU, irinotecan, and oxaliplatin), both after long-course chemoradiation.

The primary end points are clinical complete response and disease-free survival. Secondary end points include organ-preservation time, time to distant metastasis, overall survival, and the rate of adverse effects. Circulating tumor DNA status will be evaluated as an exploratory end point.

The Janus Rectal Cancer Trial will provide an answer to the key questions of what type of chemotherapy is ideal in the neoadjuvant setting, Hall explained. Data from the study will also be used to define the features of rectal adenocarcinoma that are most optimally treated with doublet vs a triplet chemotherapy, he added. There may also be opportunities to further personalize treatment and understand which types, stages, mutational burdens, and/or circulating tumor markers can inform the selection of a doublet vs a triplet, he added.

The study has fully accrued and has been completed, according to Hall.

Disclosures: Hall reported having stock and other ownership interests in Sonoptima; he holds consulting or advisory roles with Aktis Oncology and Sonoptima. He received institutional research funding as well as travel, accommodations, and expenses from Elekta. He has a patent pending for a wearable device for radiation treatment planning.