Investigators hope that a phase 2 clinical trial underway at Roswell Park Comprehensive Cancer Center and other centers across the nation will help determine whether adding irinotecan to neoadjuvant standard-of-care chemotherapy and radiation can improve the rate of complete clinical response in rectal cancer patients, enabling some of them to avoid surgery. Sponsored by the Alliance for Clinical Trials in Oncology, “The Janus Rectal Cancer Trial: A Randomized Phase II Trial Testing the Efficacy of Triplet Versus Doublet Chemotherapy to Achieve Clinical Complete Response in Patients with Locally Advanced Rectal Cancer” (NCT05610163) aims to enroll 312 patients with locally advanced disease.

Deepak Vadehra, DO, Assistant Professor of Oncology in the Department of Medicine and site principal investigator of the study at Roswell Park, explains that total neoadjuvant therapy, often called “TNT,” is the current standard of care for many patients with rectal cancer.

“TNT usually consists of two components: radiation — which typically is given with chemotherapy to sensitize the tumor, to help the radiation work better — and systemic chemotherapy with oxaliplatin,” he says. “Prior studies have shown that adding irinotecan to oxaliplatin-based chemotherapy can potentially increase the response rate.”

The randomized, open-label study has two arms. Prior to surgery, patients in both groups will undergo long-course chemoradiation therapy to promote higher sphincter preservation and lower surgical morbidity. The first group will then receive either FOLFOX (leucovorin IV, fluorouracil IV and oxaliplatin IV) or CAPOX (capecitabine PO and oxaliplatin IV). Those in the second, experimental group will receive FOLFIRINOX (leucovorin IV, fluorouracil IV, oxaliplatin IV and irinotecan IV).

“The main purpose of the JANUS trial is to investigate whether adding irinotecan to TNT increases complete clinical response,” says Dr. Vadehra. “Patients who achieve complete clinical response can be considered for nonoperative management.”

Secondarily, the study will compare the two groups’ rates of disease-free survival, organ preservation time, time to distant metastasis, overall survival and incidence of adverse events.

“We are proud to be able to offer the JANUS trial to newly diagnosed rectal cancer patients, to help advance the treatment of rectal cancer,” says Dr. Vadehra.