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+)
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
461
Investigational arm: Neoadjuvant chemotherapy mFolfirinox, 4 cycles: oxaliplatin: 85 mg/m² in 2 hours at D1 irinotecan: 180 mg/m² in 90 min at D1 folinic acid: 400 mg/m² simultaneously in 2 hours at D1 during the irinotecan infusion 5-FU: 2400 mg/m² continuous infusion during 48 hours (1200 mg/m² at D1 and D2), every 14 days during 2 months (4 cycles), then CRT (50 Gy (2 Gy/session, 25 fractions) + capecitabine 800 mg/m² twice a day 5 days/7), then surgery with TME 6-8 weeks after chemoradiation, and 4 months of adjuvant CT depending on the center's choice.
5 radiations per week of 2 Gy for 5 weeks
1600 mg/m² (800 mg/m² twice daily) for 5 weeks
disease-free survival
To compare the 3-year disease-free survival between the investigational arm and the control arm.
Time frame: 3 years
Overall survival
Overall survival will be defined as the time from randomisation to the time of occurrence of the first death regardless to its cause. Patients alive at the time of analysis will be censored at the date of the last follow up.
Time frame: 7 years
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oxaliplatine 85 mg/m² (day 1 of cycle; perfusion in 2h), folinic acid 400 mg/m² (day 1 of cycle perfusion in 2h), 5-FU (bolus 400 mg/m² in 10 min and 2400 mg/m² perfusion continuous 46h). Arm A - 12 cycles ; Arm B - 6 cycles OR Capecitabine 2500 mg/m²/day (Each cycle consists of 1250 mg/m² twice daily for D1-14 then pause therapeutic from D15-21). Arm A - 8 cycles; Arm B 4 cycles.
Centre hospitalier Universitaire d'Amiens
Amiens, France
ICO - Site Paul Papin
Angers, France
Centre hospitalier d'Auxerre
Auxerre, France
Centre Hospitalier de Beauvais
Beauvais, France
Institut de Cancérologie de Franche Comté
Besançon, France
Centre Hospitalier de Blois
Blois, France
Hopital Avicenne
Bobigny, France
Clinique Tivoli
Bordeaux, France
Hopital Saint Andre
Bordeaux, France
Institut Bergonie
Bordeaux, France
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