National, multi-center, open-label,randomized, 2-arm phase III superiority trial, comparing neoadjuvant chemotherapy (CT) with mFolfirinox followed by preoperative chemoradiotherapy (CRT), versus preoperative CRT in patients with locally advanced rectal cancer.

Methodology This is a biomedical research, national, multicenter, open-label randomized, 2-arm phase III superiority trial, comparing neoadjuvant CT with mFolfirinox then preoperative CRT, versus immediate preoperative CRT, in patients with locally advanced rectal cancer Randomized Phase III study with stopping rules Stratification : center, gender, tumor location in the rectum (<6 cm from anal verge versus ≥6 cm), initial stage (cT3 vs cT4, and cN0 vs cN+)

Inclusion Criteria:

• Histologically proven rectal adenocarcinoma
• Stages cT3 with risk of local recurrence or cT4, M0 and for which a multidisciplinary meeting recommend preoperative CRT
• Resectable tumor, or considered as potentially resectable after CRT
• No distant metastases
• Patient eligible for surgery
• Patient aged from 18 to 75 years
• World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status 0/2.
• No heart failure or coronary heart disease symptoms (even controlled).
• No peripheral neuropathy > grade 1
• No prior radiotherapy of the pelvis for any reason and no previous CT
• No major comorbidity that may preclude the delivery of treatment and no active infection (HIV or chronic hepatitis B or C).
• Adequate contraception in fertile patients.
• Adequate hematologic function
• Adequate hepatic function
• Signed written informed consent

Exclusion Criteria:

• Metastatic disease
• Unresectable rectal cancer, including prostatic involvement or extension to pelvic floor muscles
• Contraindication to 5-FU, or to oxaliplatin or to irinotecan, including Gilbert disease or genotype UGT1A1
• Medical history of chronic diarrhea or inflammatory disease of the colon or rectum
• Medical history of angina pectoris or myocardial infarction
• Progressive active infection or any other severe medical condition that could jeopardize treatment administration
• Other concomitant cancer, or medical history of cancer other than treated in situ cervical carcinoma or basocellular carcinoma or spinocellular carcinoma
• Patient included in another clinical trial testing an investigational agent.
• Pregnant or breast-feeding woman.
• Persons deprived of liberty or under guardianship or incapable of giving consent
• Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol or follow-up schedule.

Unicancer will share de-identified individual data that underlie the results reported. A decision concerning the sharing of other study documents, including protocol and statistical analysis plan will be examined upon request.

The data shared will be limit to that required for independent mandated verification of the published results, the applicant will need authorization from Unicancer for personal access, and data will only be transferred after signing of a data access agreement.

Unicancer will consider access to study data upon written detailed request sent to Unicancer, from 6 months until 5 years after publication of summary data.