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IRinotecan and Oxaliplatin for Colon Cancer in Adjuvant Setting (IROCAS)

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ClinicalTrials.gov Identifier: NCT02967289
Recruitment Status : Recruiting
First Posted : November 18, 2016
Last Update Posted : January 11, 2019
Sponsor:
Collaborator:
Canadian Cancer Trials Group
Information provided by (Responsible Party):
UNICANCER

Tracking Information
First Submitted Date  ICMJE November 9, 2016
First Posted Date  ICMJE November 18, 2016
Last Update Posted Date January 11, 2019
Actual Study Start Date  ICMJE March 27, 2017
Estimated Primary Completion Date June 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 15, 2016)
Disease Free Survival (DFS) [ Time Frame: 3 YEARS after inclusion ]
DFS : defined as the time from the date of randomization up to the date of:
  • first local, regional or distant relapse;
  • second colorectal cancer;
  • death from any cause included treatment-related death.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02967289 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 15, 2016)
  • Disease Free Survival [ Time Frame: 2 YEARS after inclusion ]
    DFS : defined as the time from the date of randomization up to the date of:
    • first local, regional or distant relapse;
    • second colorectal cancer;
    • death from any cause included treatment-related death.
  • Overall Survival [ Time Frame: 5 YEARS after inclusion ]
    Overall Survival (OS) is defined as the time from the date of randomization to the date of documented death from any cause
  • Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: 2 YEARS after inclusion ]
    Safety of the study treatment will be assessed on occurrence of Adverse Events (AEs), intake of concomitant treatments, per-treatment arising changes in physical examination, vital signs (blood pressure, pulse rate and body temperature), ECG, and clinical laboratory tests (biochemistry, haematology). Safety parameters will be graded based on NCI CTCAE v4.03 classification. The following parameters will be particularly followed: The incidence of haematological toxicities (grade 3-4, in particular neutropenia and febrile neutropenia); The incidence of GI toxicities, in particular diarrhea; The incidence of peripheral neuropathy.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE IRinotecan and Oxaliplatin for Colon Cancer in Adjuvant Setting
Official Title  ICMJE A Phase III, Randomised, International Trial Comparing mFOLFIRINOX Triplet Chemotherapy to mFOLFOX for High-risk Stage III Colon Cancer in Adjuvant Setting
Brief Summary The trial is a phase III, multicenter, open-labeled randomized trial comparing the association 5-fluorouracil, folinic acid, irinotecan and oxaliplatin (mFOLFIRINOX) versus oxaliplatin, folinic acid, 5FU (mFOLFOX 6) chemotherapy protocols in patients with high-risk stage III colon cancer in the adjuvant setting.
Detailed Description

After inclusion and non-inclusion criteria have been fulfilled and the patient consent has been obtained, the patient will be included and randomized in the trial.The maximum delay allowed between the signature of the consent form by the patient and the randomization in the study is 28 days.

The randomization procedure using minimization method will allocate the treatments mFOLFIRINOX or mFOLFOX 6 with a 1:1 ratio, and will be stratified by the following criteria:

  • Perforation or urgent surgery versus no perforation and no urgent surgery.
  • T1-T3N2 vs T4aN1 versus T4bN1 versus T4N2.
  • Right colon (right of splenic flexure) vs left colon.
  • Country (France vs Canada). Patient eligible and who have signed the informed consent will be randomized in one of the two treatments arms and will receive every 14 days their treatment for a duration of 12 cycles.

Arm A: mFOLFIRINOX Arm B: mFOLFOX 6

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Colon Cancer (High-risk Stage III: pT4N1 or pT1 to 4 N2)
Intervention  ICMJE
  • Drug: Irinotecan
    every 14 days, 12 cycles, 24 weeks, new cycle beginning on day 15: irinotecan (Campto®) 180 mg/m² on D1, IV infusion over 90 minutes to begin 30 min after folinic acid infusion is started
    Other Name: Campto
  • Drug: Folfox Protocol
    every 14 days, 12 cycles, 24 weeks, new cycle beginning on day 15: oxaliplatin (Eloxatin®) 85 mg/m² on D1, IV infusion over 2 hours, followed by folinic acid 400 mg/m² (racemic mixture) (or 200 mg/m² if L-folinic acid) IV infusion over 2 hours 5-FU 2400 mg/m²/h IV continuous infusion over 46 hours starting at the end of folinic acid infusion
    Other Name: acid folinic + oxaliplatine + 5FU
Study Arms  ICMJE
  • Experimental: Arm A
    mFOLFIRINOX Folfox Protocol + Irinotecan
    Interventions:
    • Drug: Irinotecan
    • Drug: Folfox Protocol
  • Active Comparator: Arm B
    mFOLFOX 6 Folfox Protocol
    Intervention: Drug: Folfox Protocol
Publications * Bennouna J, André T, Campion L, Hiret S, Miglianico L, Mineur L, Touchefeu Y, Artru P, Asmis T, Bouché O, Borde F, Kavan P, Lam YH, Rajpar LS, Emile JF, Jouffroy C, Gill S, Taïeb J. Rationale and Design of the IROCAS Study: Multicenter, International, Randomized Phase 3 Trial Comparing Adjuvant Modified (m) FOLFIRINOX to mFOLFOX6 in Patients With High-Risk Stage III (pT4 and/or N2) Colon Cancer-A UNICANCER GI-PRODIGE Trial. Clin Colorectal Cancer. 2019 Mar;18(1):e69-e73. doi: 10.1016/j.clcc.2018.09.011. Epub 2018 Oct 19.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 15, 2016)
640
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2026
Estimated Primary Completion Date June 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 1. Patient ≥18 years and <71 years
  • 2. Patient with ECOG ≤1
  • 3. Pathologically confirmed high-risk stage III colon adenocarcinoma, restricted to pT4N1 or pT1-4N2 tumor
  • 4. Curative R0 surgical resection within 42 days before randomization
  • 5. Patients who have undergone surgery for colon cancer, defined as a tumor location >12 cm from the anal verge by endoscopy and/or above the peritoneal reflection at surgery (high rectum), without gross or microscopic evidence of residual disease after surgery with curative intent
  • 6. Start of study drug treatment has to be performed less than 56 days after surgery
  • 7. No prior chemotherapy
  • 8. No prior abdominal or pelvic irradiation
  • 9. Patient with adequate organ function: Absolute neutrophil count (ANC) ≥2 x 10⁹/L Haemoglobin ≥9 g/dL Platelets (PTL) ≥100 x 10⁹/L AST/ALT ≤2.5 x ULN Alkaline phosphatase ≤2.5 x ULN Total Bilirubin ≤1.5 x ULN (Upper Limit of Normal) Creatinine clearance ≥50 mL/min (Cockcroft and Gault formula) Kalemia, magnesemia, calcemia ≥1 LLN (Lower Limit of Normal) Carcinoembryogenic antigen (CEA) ≤10 ng/mL after surgery (during screening period)
  • 10. Adequate contraception if applicable.
  • 11. Patient able and willing to comply with study procedures as per protocol
  • 12. Patient able to understand and willing to sign and date the written voluntary informed consent form at screening visit prior to any protocol-specific procedures
  • 13. Public or private health insurance coverage
  • 14. Life expectancy of > or = at 5 years

Exclusion Criteria:

  • 1. Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to study treatment start. Incompletely healed wounds or anticipation of the need for major surgical procedure during the course of the study
  • 2. Metastatic disease
  • 3. Presence of inflammatory bowel disease and/or ileus
  • 4. Known hypersensitivity reaction to any of the components of study treatments
  • 5. Pregnancy (absence to be confirmed by β-hCG test) or breast-feeding period
  • 6. Clinically relevant coronary artery disease or history of myocardial infarction in the last 12 months, or high risk of uncontrolled arrhythmia (for men: QT/QTc ≥450 msec, for women: QT/QTc ≥470 msec)
  • 7. Previous malignancy in the last 5 years except curative treated basal cell carcinoma of the skin and/or in situ carcinoma of the cervix
  • 8. Medical, geographical, sociological, psychological or legal conditions that would not permit the patient to complete the study or sign informed consent
  • 9. History or current evidence on physical examination of central nervous system disease or peripheral neuropathy grade ≥1 Common Toxicity Criteria for Adverse Events (CTCAE) v4.03
  • 10. Any significant disease which, in the investigator's opinion, would exclude the patient from the study
  • 11. Known DPD deficiency or UGT1A1 homozygous 7/7
  • 12. Patients already included in another therapeutic trial involving an experimental drug
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 71 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Beata JUZYNA 0033.1.71.93.63.66 b-juzyna@unicancer.fr
Contact: Veronica PEZZELLZ v-pezzella@unicancer.fr
Listed Location Countries  ICMJE Canada,   France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02967289
Other Study ID Numbers  ICMJE UC-0110/1609_PRODIGE52/UCGI29
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  ICMJE Not Provided
Responsible Party UNICANCER
Study Sponsor  ICMJE UNICANCER
Collaborators  ICMJE Canadian Cancer Trials Group
Investigators  ICMJE
Study Chair: Jaafar BENNOUNA, Professor ICO René Gauducheau, Nantes - Angers
Study Chair: Julien TAIEB, Professor Hôpital Européen Georges-Pompidou, PARIS
Study Chair: Thierry ANDRE, Professor AP-HP Hôpital Saint-Antoine, PARIS
PRS Account UNICANCER
Verification Date October 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP