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

Study Overview
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Brief Summary
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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

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

Conditions
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Metastatic Colorectal Cancer

Intervention / Treatment
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* Drug: FOLFOXIRI plus bevacizumab


Participation Criteria
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Eligibility Criteria
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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.

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| BRAF mutant mCRC<br> | Drug: FOLFOXIRI plus bevacizumab<br>* BEVACIZUMAB 5 mg/Kg i.v. over 30', day 1 followed by IRINOTECAN 165 mg/sqm i.v. over 1-h, day 1 followed by OXALIPLATIN 85 mg/sqm i.v. over 2-h, day 1 concomitantly with l-LV 200 mg/sqm i.v. over 2-h, day 1 followed by 5-FLUOROURACIL 3200 mg/sqm i.v. 48-h continuous infusion, starting on day 1 Cycles repeated every 2 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival |  | About 24-30 months (From treatment initiation to evidence of progression or death from any cause) |