Clinical Trials /

IRinotecan and Oxaliplatin for Colon Cancer in Adjuvant Setting

NCT02967289

Description:

The trial is a phase III, multicenter, open-labeled randomized trial comparing the association 5-fluorouracil (5-FU), folinic acid, irinotecan and oxaliplatin (mFOLFIRINOX) versus oxaliplatin, folinic acid, 5-FU (mFOLFOX 6) chemotherapy protocols in patients with high-risk stage III colon cancer in the adjuvant setting.

Related Conditions:
  • Colon Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: IRinotecan and Oxaliplatin for Colon Cancer in Adjuvant Setting
  • Official Title: A Phase III, Randomised, International Trial Comparing mFOLFIRINOX Triplet Chemotherapy to mFOLFOX for High-risk Stage III Colon Cancer in Adjuvant Setting

Clinical Trial IDs

  • ORG STUDY ID: UC-0110/1609_PRODIGE52/UCGI29
  • NCT ID: NCT02967289

Conditions

  • Colon Cancer (High-risk Stage III: pT4N1 or pT1 to 4 N2)

Interventions

DrugSynonymsArms
IrinotecanCamptoArm A
Folfox Protocolacid folinic + oxaliplatine + 5-FUArm A

Purpose

The trial is a phase III, multicenter, open-labeled randomized trial comparing the association 5-fluorouracil (5-FU), folinic acid, irinotecan and oxaliplatin (mFOLFIRINOX) versus oxaliplatin, folinic acid, 5-FU (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
    

Trial Arms

NameTypeDescriptionInterventions
Arm AExperimentalmFOLFIRINOX Folfox Protocol + Irinotecan
  • Irinotecan
  • Folfox Protocol
Arm BActive ComparatormFOLFOX 6 Folfox Protocol
  • Folfox Protocol

Eligibility Criteria

        Inclusion Criteria:

          -  1. Patient ≥18 years and <71 years

          -  2. Patient with Eastern Cooperative Oncology Group (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 ≥100 x 10⁹/L

               -  Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤2.5 x ULN

               -  Alkaline phosphatase ≤2.5 x upper limit of normal (ULN)

               -  Total Bilirubin ≤1.5 x ULN

               -  Creatinine clearance ≥50 mL/min (Cockcroft and Gault formula)

               -  Kalemia, magnesemia, calcemia ≥1 lower limit of normal (LLN)

               -  Carcinoembryonic 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 ≥ 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
      
Maximum Eligible Age:71 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Disease Free Survival (DFS)
Time Frame:3 YEARS after inclusion
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Disease Free Survival
Time Frame:2 YEARS after inclusion
Safety Issue:
Description: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.
Measure:Overall Survival
Time Frame:5 YEARS after inclusion
Safety Issue:
Description:Overall Survival (OS) is defined as the time from the date of randomization to the date of documented death from any cause
Measure:Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Time Frame:2 YEARS after inclusion
Safety Issue:
Description: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.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:UNICANCER

Trial Keywords

  • colon
  • cancer
  • stage 3
  • high-risk
  • mFolfirinox
  • mFolfox6
  • adjuvant

Last Updated

October 25, 2019