Cancer of the Rectum
Conditions
Keywords
rectum, cancer, locally advanced
Brief summary
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.
Detailed description
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+)
Interventions
DRUGmFolfirinox
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.
RADIATIONRadiotherapy 50 Gy
5 radiations per week of 2 Gy for 5 weeks
DRUGCapecitabine
1600 mg/m² (800 mg/m² twice daily) for 5 weeks
PROCEDURETME surgery
DRUGmFolfox6 or capecitabine
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.
Sponsors
UNICANCER
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| disease-free survival | 3 years | To compare the 3-year disease-free survival between the investigational arm and the control arm. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival | 7 years | 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. |
Countries
France
Outcome results
None listed