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

Study Overview
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Brief Summary
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National trial, multicenter, randomized, phase II assessing FOLFIRINOX + Panitumumab versus mFOLFOX6 + Panitumumab in metastatic colorectal cancer patients selected by RAS and B-RAF status from circulating DNA analysis. Evaluation of complete response rate on treatment combining FOLFIRINOX and panitumumab.

Detailed Description
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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)

Official Title
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Phase II Randomized Study Comparing FOLFIRINOX + Panitumumab Versus mFOLFOX6 + Panitumumab in Metastatic Colorectal Cancer Patients Selected by RAS and B-RAF Status From Circulating DNA Analysis

Conditions
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Metastatic Colorectal Cancer

Intervention / Treatment
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* Drug: Panitumumab, oxaliplatin, folinic acid, 5-fluoruracil
* Drug: Panitumumab, oxaliplatin, folinic acid, 5-fluoruracil, irinotecan


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: National trial, multicenter, randomized, phase II assessing FOLFIRINOX + Panitumumab versus mFOLFOX6 + Panitumumab in metastatic colorectal cancer patients selected by RAS and B-RAF status from circulating DNA analysis.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A=Experimental group<br>FOLFIRINOX + Panitumumab oxaliplatin 85 mg/m² IV infusion over 2 hours immediately followed by folinic acid 400 mg/m² given as a 2-hour intravenous (IV) infusion with the addition, after 30 minutes of irinotecan 150 mg/m² given as a 90-minute intravenous infusion through a Y-connector immediately followed by fluorouracil 400 mg/m² IV bolus then 5-fluoruracil (5-FU) 2400 mg/m² over 46 hours continuous infusion. | Drug: Panitumumab, oxaliplatin, folinic acid, 5-fluoruracil, irinotecan<br> <br> |
| Active Comparator: B=Control group<br>mFOLFOX6 + Panitumumab mFOLFOX6 every 2 weeks: oxaliplatin 85 mg/m² IV infusion over 2 hours immediately followed by folinic acid 400 mg/m² IV infusion over 2 hours followed by fluorouracil 400 mg/m² IV bolus then 5-FU 2400 mg/m² over 46 hours continuous infusion. | Drug: Panitumumab, oxaliplatin, folinic acid, 5-fluoruracil<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of complete response rate on treatment combining FOLFIRINOX and panitumumab. |  | 12 months after inclusion |