Randomized Phase III Study Comparing Preoperative Chemoradiotherapy Alone Versus Neoadjuvant Chemotherapy With Folfirinox Regimen Followed by Preoperative Chemoradiotherapy for Patients With Resectable Locally Advanced Rectal Cancer
Overview
- Phase
- Phase 3
- Intervention
- Radiotherapy 50 Gy
- Conditions
- Cancer of the Rectum
- Sponsor
- UNICANCER
- Enrollment
- 461
- Locations
- 35
- Primary Endpoint
- disease-free survival
- Status
- Completed
- Last Updated
- 10 months ago
Overview
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+)
Investigators
Eligibility Criteria
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/
- •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
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
Arms & Interventions
Arm A : Radiotherapy + capecitabine
Chemoradiotherapy 5 weeks (50 Grays (Gy), 2 Gy/session ; 25 fractions) + capecitabine 800 mg/m² twice daily 5 days/7, excluding weekends), then 6-8 weeks after chemoradiation, surgery with total mesorectal excision (TME), followed by adjuvant chemotherapy for 6 months, either mFolfox6 or capecitabine, depending on the center's choice.
Intervention: Radiotherapy 50 Gy
Arm A : Radiotherapy + capecitabine
Chemoradiotherapy 5 weeks (50 Grays (Gy), 2 Gy/session ; 25 fractions) + capecitabine 800 mg/m² twice daily 5 days/7, excluding weekends), then 6-8 weeks after chemoradiation, surgery with total mesorectal excision (TME), followed by adjuvant chemotherapy for 6 months, either mFolfox6 or capecitabine, depending on the center's choice.
Intervention: Capecitabine
Arm A : Radiotherapy + capecitabine
Chemoradiotherapy 5 weeks (50 Grays (Gy), 2 Gy/session ; 25 fractions) + capecitabine 800 mg/m² twice daily 5 days/7, excluding weekends), then 6-8 weeks after chemoradiation, surgery with total mesorectal excision (TME), followed by adjuvant chemotherapy for 6 months, either mFolfox6 or capecitabine, depending on the center's choice.
Intervention: TME surgery
Arm A : Radiotherapy + capecitabine
Chemoradiotherapy 5 weeks (50 Grays (Gy), 2 Gy/session ; 25 fractions) + capecitabine 800 mg/m² twice daily 5 days/7, excluding weekends), then 6-8 weeks after chemoradiation, surgery with total mesorectal excision (TME), followed by adjuvant chemotherapy for 6 months, either mFolfox6 or capecitabine, depending on the center's choice.
Intervention: mFolfox6 or capecitabine
Arm B : Chemotherapy then radiochemotherapy
Drug: Chemotherapy mFolfirinox Investigational arm: Neoadjuvant CT mFolfirinox, 6 cycles (ca. 3 months; each cycle = 2 weeks): 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-fluorouracil (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 followed by 5 weeks of chemoradiotherapy 50 Gy (2 Gy/session, 5 sessions per week) + capecitabine 800 mg/m² twice daily 5 days/7), then surgery with TME 6-8 weeks after chemoradiation, followed by 3 months of adjuvant chemotherapy, either mFolfox6 or capecitabine depending on the center's choice.
Intervention: mFolfirinox
Arm B : Chemotherapy then radiochemotherapy
Drug: Chemotherapy mFolfirinox Investigational arm: Neoadjuvant CT mFolfirinox, 6 cycles (ca. 3 months; each cycle = 2 weeks): 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-fluorouracil (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 followed by 5 weeks of chemoradiotherapy 50 Gy (2 Gy/session, 5 sessions per week) + capecitabine 800 mg/m² twice daily 5 days/7), then surgery with TME 6-8 weeks after chemoradiation, followed by 3 months of adjuvant chemotherapy, either mFolfox6 or capecitabine depending on the center's choice.
Intervention: Radiotherapy 50 Gy
Arm B : Chemotherapy then radiochemotherapy
Drug: Chemotherapy mFolfirinox Investigational arm: Neoadjuvant CT mFolfirinox, 6 cycles (ca. 3 months; each cycle = 2 weeks): 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-fluorouracil (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 followed by 5 weeks of chemoradiotherapy 50 Gy (2 Gy/session, 5 sessions per week) + capecitabine 800 mg/m² twice daily 5 days/7), then surgery with TME 6-8 weeks after chemoradiation, followed by 3 months of adjuvant chemotherapy, either mFolfox6 or capecitabine depending on the center's choice.
Intervention: Capecitabine
Arm B : Chemotherapy then radiochemotherapy
Drug: Chemotherapy mFolfirinox Investigational arm: Neoadjuvant CT mFolfirinox, 6 cycles (ca. 3 months; each cycle = 2 weeks): 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-fluorouracil (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 followed by 5 weeks of chemoradiotherapy 50 Gy (2 Gy/session, 5 sessions per week) + capecitabine 800 mg/m² twice daily 5 days/7), then surgery with TME 6-8 weeks after chemoradiation, followed by 3 months of adjuvant chemotherapy, either mFolfox6 or capecitabine depending on the center's choice.
Intervention: TME surgery
Arm B : Chemotherapy then radiochemotherapy
Drug: Chemotherapy mFolfirinox Investigational arm: Neoadjuvant CT mFolfirinox, 6 cycles (ca. 3 months; each cycle = 2 weeks): 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-fluorouracil (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 followed by 5 weeks of chemoradiotherapy 50 Gy (2 Gy/session, 5 sessions per week) + capecitabine 800 mg/m² twice daily 5 days/7), then surgery with TME 6-8 weeks after chemoradiation, followed by 3 months of adjuvant chemotherapy, either mFolfox6 or capecitabine depending on the center's choice.
Intervention: mFolfox6 or capecitabine
Outcomes
Primary Outcomes
disease-free survival
Time Frame: 3 years
To compare the 3-year disease-free survival between the investigational arm and the control arm.
Secondary Outcomes
- Overall survival(7 years)