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

Metastatic Colorectal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01437618
• Other study ID #: BRAF-0809-TRIBV
• Status: Completed
• Phase: N/A
• First received: July 12, 2011
• Last updated: September 20, 2011
• Start date: June 2009
• Est. completion date: May 2011

Study information

• Verified date: September 2011
• Source: Azienda Ospedaliero, Universitaria Pisana
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: The Italian Medicines Agency
• Study type: Observational

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: May 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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.

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Cancer

Intervention

Drug:
• FOLFOXIRI plus bevacizumab
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

Locations

Country	Name	City	State
Italy	Azienda Ospedaliero-Universitaria Pisana	Pisa

Sponsors (1)

Lead Sponsor	Collaborator
Azienda Ospedaliero, Universitaria Pisana

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-Free Survival		About 24-30 months (From treatment initiation to evidence of progression or death from any cause)	No