Comparison FOLFIRINOX Panitumumab vs mFOLFOX6 Panitumumab in RAS/B-RAF Wild-type Metastatic Colorectal Cancer Patients

PRIMARY OBJECTIVE: Evaluation of complete response rate on treatment combining FOLFIRINOX and panitumumab

SECONDARY OBJECTIVE(S):

• Overall Survival
• Progression free survival
• Secondary resection
• Early tumor shrinkage (ETS)
• Depth of response (DpR)
• Safety profile (NCI-CTCAE v4.03 classification)
• Diagnostic performance of ccfDNA analysis compared to the tumor-tissue analysis (current gold standard)

Inclusion criteria

• Age between 18 and 75 years
• ECOG PS between 0 and 1
• Histologically confirmed adenocarcinoma of the colon or rectum
• Untreated synchronous or metachronous metastatic disease deemed unresectable with curative intent
• K-Ras (codons 12, 13, 59, 61, 117, 146), N-Ras (codons 12, 13, 59, 61) and B-Raf (codon 600) wild-type tumor status according to plasma analysis of circulating cell free DNA by Intplex technology
• Measurable disease according to RECIST version 1.1
• Adequate hematologic, hepatic and renal functions:

• Absolute neutrophil count (ANC) ≥2 x 109/L
• Haemoglobin ≥9 g/dL
• Platelets (PTL) ≥100 x 109/L
• AST/ALT ≤5 x ULN
• Alkaline phosphatase ≤2.5 x ULN
• Bilirubin ≤1.5 x ULN
• Creatinine clearance ≥50 mL/min (Cockcroft and Gault formula)
• Life expectancy of at least 3 months
• Adequate contraception if applicable
• Patient affiliated to a social security regimen
• Patient information and signed written consent form
• Uracilemia < 16 ng/ml

Exclusion criteria

• History of other malignancy within the previous 5 years (except for appropriately treated in-situ cervix carcinoma and non-melanoma skin carcinoma)
• Adjuvant treatment with oxaliplatin
• Previous treatment for metastatic disease
• Patients who received any chemo- and/or radiotherapy within 15 days from the date of blood sampling for the RAS and BRAF test
• Brain metastases
• Patients with a history of severe or life-threatening hypersensitivity to the active substances or to any of the excipients delivered in this study
• Patient with history of pulmonary fibrosis or interstitial pneumonitis
• Previous organ transplantation, HIV or other immunodeficiency syndromes
• Concomitant medications/comorbidities that may prevent the patient from receiving study treatment as uncontrolled intercurrent illness (for instance: active infection, active inflammatory disorders, inflammatory bowel disease, intestinal obstruction, symptomatic congestive heart failure, uncontrolled hypertension…)
• Persistent peripheral neuropathy >grade1 (NCI CT v4.03)
• Ionic disorders as:

• Kalemia ≤1 x LLN
• Magnesemia <0.5mmol/L
• Calcemia <2mmol/L
• Patient with known dihydropyrimidine dehydrogenase deficiency
• QT/QTc>450msec for men and >470msec for women
• Patient with contraindication for trial drugs (investigators have to refer to SmPC drugs, see Appendix 7)
• Concomitant intake of St. John's wort
• Other concomitant cancer
• Participation in another therapeutic trial
• Pregnant woman or lactating woman
• Patients with psychological, familial, sociological or geographical condition hampering compliance with the study protocol and follow-up schedule
• Legal incapacity or limited legal capacity