NCT05610163

Testing the Addition of an Anti-Cancer Drug, Irinotecan, to the Standard Chemotherapy Treatment (FOLFOX) After Long-Course Radiation Therapy for Advanced-Stage Rectal Cancers to Improve the Rate of Complete Response and Long-Term Rates of Organ Preservation

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

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 783 (actual)
• Sponsor: Alliance for Clinical Trials in Oncology · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase II trial compares the effect of irinotecan versus oxaliplatin after long-course chemoradiation in patients with stage II-III rectal cancer. Combination chemotherapy drugs, such as FOLFIRINOX (fluorouracil, irinotecan, leucovorin, and oxaliplatin), FOLFOX (leucovorin, fluorouracil, oxaliplatin, and irinotecan ), and CAPOX (capecitabin and oxaliplatin) work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. FOLFOX or CAPOX are used after chemoradiation as usual treatment for rectal cancer. Giving FOLFIRINOX after chemoradiation may increase the response rate and lead to higher rates of clinical complete response (with a chance of avoiding surgery) compared to FOLFOX or CAPOX after chemoradiation in patients with locally advanced rectal cancer.

Detailed description

PRIMARY OBJECTIVE: I. To evaluate and compare the clinical complete response (cCR) rates in patients with locally advanced rectal cancer treated with neoadjuvant long-course neoadjuvant radiotherapy (LCRT) followed by neoadjuvant modified fluorouracil, irinotecan, leucovorin, and oxaliplatin (mFOLFIRINOX) versus neoadjuvant LCRT followed by neoadjuvant modified leucovorin , fluorouracil, and oxaliplatin (mFOLFOX6). SECONDARY OBJECTIVES: I. To evaluate and compare organ-preservation-time (OPT) between two treatment arms. II. To evaluate and compare the disease-free survival (DFS) time between the two treatment arms. III. To evaluate and compare time to distant metastasis between two treatment arms. IV. To evaluate and compare overall survival (OS) between two treatment arms. V. To evaluate and compare toxicity profiles of total neoadjuvant therapy (TNT) between two treatment arms. EXPLORATORY OBJECTIVE: I. Evaluation of circulating tumor deoxyribonucleic acid (ctDNA) kinetics during neoadjuvant therapy \& surveillance and to correlate with radiographic, pathologic, and clinical outcomes. OUTLINE: Patients are randomized to 1 of 2 arms. GROUP I: Patients receive long-course chemoradiation therapy on study and then receive either: FOLFOX regimen consisting of leucovorin intravenously (IV), fluorouracil IV, and oxaliplatin IV or CAPOX consisting of capecitabine orally (PO), and oxaliplatin IV on study. Patients undergo computed tomography (CT) scan, magnetic resonance imaging (MRI), and biospecimen collection throughout the trial. Patients also undergo sigmoidoscopy throughout the trial and biopsy during screening. GROUP II: Patients receive long-course chemoradiation therapy on study and then receive FOLFIRINOX regimen consisting of leucovorin IV, fluorouracil IV, irinotecan IV, and oxaliplatin IV on study. Patients undergo CT scan, MRI scan, and blood specimen collection throughout the trial. Patients undergo sigmoidoscopy throughout the trial and biopsy during screening.

Conditions

• Locally Advanced Rectal Carcinoma
• Stage II Rectal Cancer AJCC v8
• Stage III Rectal Cancer AJCC v8

Interventions

Type	Name	Description
DRUG	Capecitabine	Given PO
DRUG	5-fluorouracil	Given IV
DRUG	Leucovorin calcium	Given IV
DRUG	Irinotecan	Given IV
DRUG	Oxaliplatin	Given IV
RADIATION	Long Course Chemoradiotherapy	Receive LCRT
PROCEDURE	Computed Tomography	undergo CT
PROCEDURE	Magnetic Resonance Imaging	undergo MRI
PROCEDURE	Sigmoidoscopy	undergo sigmoidoscopy
PROCEDURE	biopsy	undergo biopsy

Timeline

• Start date: 2022-12-08
• Primary completion: 2026-09-30
• Completion: 2033-09-30
• First posted: 2022-11-09
• Last updated: 2025-09-08

Locations

685 sites across 2 countries: United States, Puerto Rico