Efficacy of Neoadjuvant Folfirinox Regimen in Patients With Resectable Locally Advanced Rectal Cancer (Néofirinox)

• ClinicalTrials.gov Identifier: NCT01804790
• Recruitment Status: Active, not recruiting
• First Posted: March 5, 2013
• Last Update Posted: August 31, 2023
• Sponsor: UNICANCER
• Information provided by (Responsible Party): UNICANCER

Tracking Information

• First Submitted Date: March 1, 2013
• First Posted Date: March 5, 2013
• Last Update Posted Date: August 31, 2023
• Actual Study Start Date: January 2012
• Actual Primary Completion Date: September 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 4, 2013)

disease-free survival [ Time Frame: 3 years ]

To compare the 3-year disease-free survival between the investigational arm and the control arm.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 4, 2013)

Overall survival [ Time Frame: 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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Efficacy of Neoadjuvant Folfirinox Regimen in Patients With Resectable Locally Advanced Rectal Cancer
• Official Title: 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
• 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+)
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Cancer of the Rectum

Intervention

• Drug: mFolfirinox
  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.
• Radiation: Radiotherapy 50 Gy
  5 radiations per week of 2 Gy for 5 weeks
• Drug: Capecitabine
  1600 mg/m² (800 mg/m² twice daily) for 5 weeks
• Procedure: TME surgery
• Drug: mFolfox6 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.

Study Arms

• Active Comparator: 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.
  Interventions:

  • Radiation: Radiotherapy 50 Gy
  • Drug: Capecitabine
  • Procedure: TME surgery
  • Drug: mFolfox6 or capecitabine
• Experimental: 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.

  Interventions:

  • Drug: mFolfirinox
  • Radiation: Radiotherapy 50 Gy
  • Drug: Capecitabine
  • Procedure: TME surgery
  • Drug: mFolfox6 or capecitabine

• Publications *: Conroy T, Bosset JF, Etienne PL, Rio E, Francois E, Mesgouez-Nebout N, Vendrely V, Artignan X, Bouche O, Gargot D, Boige V, Bonichon-Lamichhane N, Louvet C, Morand C, de la Fouchardiere C, Lamfichekh N, Juzyna B, Jouffroy-Zeller C, Rullier E, Marchal F, Gourgou S, Castan F, Borg C; Unicancer Gastrointestinal Group and Partenariat de Recherche en Oncologie Digestive (PRODIGE) Group. Neoadjuvant chemotherapy with FOLFIRINOX and preoperative chemoradiotherapy for patients with locally advanced rectal cancer (UNICANCER-PRODIGE 23): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2021 May;22(5):702-715. doi: 10.1016/S1470-2045(21)00079-6. Epub 2021 Apr 13.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: September 26, 2019): 461
• Original Estimated Enrollment (submitted: March 4, 2013): 460
• Estimated Study Completion Date: May 2025
• Actual Primary Completion Date: September 2019 (Final data collection date for primary outcome measure)

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 0/2.
• 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France

Administrative Information

• NCT Number: NCT01804790
• Other Study ID Numbers: PRODIGE 23 - UCGI 23; 2011-004406-25 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: 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.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Time Frame: 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.
• Access Criteria: 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.

• Current Responsible Party: UNICANCER
• Original Responsible Party: Same as current
• Current Study Sponsor: UNICANCER
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Thierry CONROY, PROF; centre Alexis Vautrin les Nancy

• PRS Account: UNICANCER
• Verification Date: August 2023