Clinical trial NCT01437618: First-line FOLFOXIRI Plus Bevacizumab in BRAF Mutant Metastatic Colorectal Cancer
Official title: FOLFOXIRI Plus Bevacizumab as First-line Treatment for BRAF V600E Mutant Metastatic Colorectal Cancer: a Prospective Evaluation
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Metastatic Colorectal Cancer
Lead sponsor: Azienda Ospedaliero, Universitaria Pisana
Sponsor class: OTHER
First posted: 2011-09-21
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: BRAF mutant mCRC

Brief summary: 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


Eligibility criteria: 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.

Primary outcomes:
measure: Progression-Free Survival
timeFrame: About 24-30 months (From treatment initiation to evidence of progression or death from any cause)
Secondary outcomes:
Other outcomes:
Locations:
city: Pisa
country: Italy
facility: Azienda Ospedaliero-Universitaria Pisana
Study officials:
References:
citation: Loupakis F, Cremolini C, Salvatore L, Masi G, Sensi E, Schirripa M, Michelucci A, Pfanner E, Brunetti I, Lupi C, Antoniotti C, Bergamo F, Lonardi S, Zagonel V, Simi P, Fontanini G, Falcone A. FOLFOXIRI plus bevacizumab as first-line treatment in BRAF mutant metastatic colorectal cancer. Eur J Cancer. 2014 Jan;50(1):57-63. doi: 10.1016/j.ejca.2013.08.024. Epub 2013 Oct 15.