Patient case: 68-year-old male with colon cancer; genetic feature: MLH1 methylation suppression (microsatellite instability)

Clinical trial: IRinotecan and Oxaliplatin for Colon Cancer in Adjuvant Setting

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

Eligibility: 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

Relevance to patient case: not relevant