Chemoradiation and Consolidation Chemotherapy With or Without Oxaliplatin for Distal Rectal Cancer and Watch and Wait

Background: Neoadjuvant chemoradiation (nCRT) has been considered the preferred initial treatment strategy for distal rectal cancer. Advantages of this approach include improved local control after radical surgery but also the opportunity for organ preserving strategies (Watch and Wait - WW). Consolidation chemotherapy (cCT) regimens using fluoropyrimidine-based with or without oxaliplatin following nCRT have demonstrated to increase complete response and organ preservation rates among these patients. However, the benefit of adding oxaliplatin to cCt compared to fluoropyrimidine alone regimens in terms of primary tumor response remains unclear. Since oxaliplatin-treatment may be associated with considerable toxicity, it becomes imperative to understand the benefit of its incorporation into standard cCT regimens in terms of primary tumor response. The aim of the present trial is to compare the outcomes of 2 different cCT regimens following nCRT (fluoropyrimidine-alone versus fluoropyrimidine+oxaliplatin) for patients with distal rectal cancer. Methods: In this multi-centre study, patients with magnetic resonance-defined distal rectal tumors will be randomized on a 1:1 ratio to receive long-course chemoradiation (54Gy) followed by cCT with fluoropyrimidine alone versus fluoropyrimidine+oxaliplatin. Magnetic resonance (MR) will be analyzed centrally prior to patient inclusion and randomization. mrT2-3N0-1 tumor located no more than 1cm above the anorectal ring determined by sagittal views on MR will be eligible for the study. Tumor response will be assessed after 12 weeks from radiotherapy (RT) completion. Patients with clinical complete response (clinical, endoscopic and radiological) will be enrolled in an organ-preservation program (WW). The primary endpoint of this trial is decision to organ-preservation surveillance (WW) at 18 weeks from RT completion. Discussion: Long-course nCRT with cCT is associated with improved complete response rates and may be a very attractive alternative to increase the chances for organ-preservation strategies. Fluoropyrimidine-based cCT with or without oxaliplatin has never been investigated in the setting of a randomized trial to compare clinical response rates and the possibility of organ-preservation. The outcomes of this study may significantly impact clinical practice of patients with distal rectal cancer interested in organ-preservation.

NCT Number	NCT05000697
Lead Sponsor	Hospital Alemão Oswaldo Cruz
Conditions	Rectal Cancer, Consolidation
Enrollment	216 participants
Start Date	2021-07-14
Primary Completion	2027-04 (estimated)
Study Completion	2027-04 (estimated)
Updated on ClinicalTrials.gov	2024-11-27