First-line FOLFOXIRI Plus Bevacizumab in BRAF Mutant Metastatic Colorectal Cancer

FOLFOXIRI Plus Bevacizumab as First-line Treatment for BRAF V600E Mutant Metastatic Colorectal Cancer: a Prospective Evaluation

The purpose of this study is to prospectively verify if FOLFOXIRI plus bevacizumab as first-line treatment could be considered a promising approach to improve the outcome of BRAF mutant metastatic colorectal cancer patients

Inclusion Criteria:

• Histologically confirmed colorectal adenocarcinoma;
• Availability of formalin-fixed paraffin embedded tumor block from primary and/or metastasis;
• BRAF V600E mutant status of primary colorectal cancer and/or related metastasis;
• Unresectable and measurable metastatic disease according to RECIST criteria;
• Male or female, aged > 18 years and < 75 years;
• ECOG PS < 2 if aged < 71 years;
• ECOG PS = 0 if aged 71-75 years;
• Life expectancy of more than 3 months;
• Adequate haematological function: ANC ≥ 1.5 x 10^9/L; platelets ≥ 100 x 10^9/L, Hb ≥ 9 g/dL;
• Adequate liver function: serum bilirubin ≤ 1.5 x ULN; alkaline phosphatase and transaminases ≤ 2.5 x ULN (in case of liver metastases ≤ 5 x ULN);
• Serum creatinine ≤ 1.5 x ULN;
• Previous adjuvant chemotherapy is allowed if more than 12 months have elapsed between the end of adjuvant therapy and first relapse;
• At least 6 weeks from prior extended radiotherapy and 4 weeks from surgery;
• Written informed consent to experimental treatment and molecular analyses.

Exclusion Criteria:

• Presence or history of CNS metastasis;
• Serious, non-healing wound, ulcer, or bone fracture;
• Evidence of bleeding diathesis or coagulopathy;
• Uncontrolled hypertension;
• Clinically significant (i.e. active) cardiovascular disease for example cerebrovascular accidents (CVA) (≤6 months before treatment start), myocardial infarction (≤ 6 months before treatment start), unstable angina, NYHA ≥ grade 2 chronic heart failure (CHF), uncontrolled arrhythmia;
• Current or recent (within 10 days prior to study treatment start) ongoing treatment with anticoagulants for therapeutic purposes;
• Chronic, daily treatment with high-dose aspirin (>325 mg/day);
• Symptomatic peripheral neuropathy ≥ 2 grade NCIC-CTG criteria;
• Active uncontrolled infections;
• Treatment with any investigational drug within 30 days prior to enrolment;
• Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of curatively treated basal and squamous cell carcinoma of the skin or in situ cancer of the cervix;
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study treatment start;
• Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome;
• Fertile women (< 2 years after last menstruation) and men of childbearing potential not willing to use effective means of contraception.