A PHASE III RANDOMIZED TRIAL OF FOLFOXIRI + BEVACIZUMAB VERSUS FOLFIRI + BEVACIZUMAB AS FIRST-LINE TREATMENT FOR METASTATIC COLORECTAL CANCER - TRIBE
- Conditions
- colorectal cancerMedDRA version: 9.1Level: HLGTClassification code 10017990Term: Malignant and unspecified neoplasms gastrointestinal NEC
- Registration Number
- EUCTR2008-001537-10-IT
- Lead Sponsor
- G.O.N.O. - GRUPPO ONCOLOGICO NORD OVEST
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- Not specified
Histologically proven diagnosis of colorectal cancer
Not resectable metastatic colorectal cancer not previously treated with chemotherapy for metastatic disease
At least one measurable lesion according to RECIST criteria
Age 18-75 years
ECOG PS < 2 if age < 70 years, ECOG PS = 0 if age = 71-75 years
Life expectancy of at least 12 weeks
Neutrophils ³1.5 x 109/L, Platelets ³100 x 109/L, Hgb >9 g/dl
Total bilirubin £1.5 time the upper-normal limits (UNL) of the Institutional normal values and ASAT (SGOT) and/or ALAT (SGPT) £2.5 x UNL, or £5 x UNL in case of liver metastases, alkaline phosphatase £2.5 x UNL, £5 x UNL in case of liver metastases.
Creatinine clearance >50 mL/min or serum creatinine £1.5 x UNL
Urine dipstick of proteinuria <2+. Patients discovered to have ³2+ proteinuria on dipstick urinalysis at baseline, should undergo a 24-hour urine collection and must demonstrate £1 g of protein/24 hr.
Written informed consent.
Patients must be accessible for treatment and follow up. Patients registered on this trial must be treated and followed at the participating Center
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
Radiotherapy to any site within 4 weeks before the study.
Untreated brain metastases or spinal cord compression or primary brain tumours.
History or evidence upon physical examination of CNS disease unless adequately treated (e.g., seizure not controlled with standard medical therapy or history of stroke).
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 (≤6 months), myocardial infarction (≤ 6 months), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication.
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).
Treatment with any investigational drug within 30 days prior to enrolment.
Patients with known allergy to Chinese hamster ovary cell proteins, or any of the components of the study medications.
Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of basal and squamous cell carcinoma or cervical cancer in situ.
Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study treatment start, or anticipation of the need for major surgical procedure during the course of the study.
Lack of physical integrity of the upper gastrointestinal tract, malabsorption syndrome, or inability to take oral medication.
Pregnant or lactating women. Women of childbearing potential with either a positive or no pregnancy test at baseline. Postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential. Sexually active males and females (of childbearing potential) unwilling to practice contraception during the study.
Symptomatic peripheral neuropathy ³ grade 1 according the NCI Common Toxicity Criteria.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To compare the progression free survival of bevacizumab in combination with oxaliplatin, irinotecan and infusional 5FU/LV (?GONO? FOLFOXIRI regimen) to bevacizumab in combination with irinotecan and 5FU/LV (FOLFIRI regimen).;Secondary Objective: To evaluate the safety profile including long-term adverse events of bevacizumab in combination with FOLFOXIRI or FOLFIRI.<br>To compare the overall response rate, duration of response, secondary R0-surgery rates of metastases and overall survival between treatment arms.<br>To evaluate potential surrogate markers predictive of bevacizumab activity;Primary end point(s): progression-free survival
- Secondary Outcome Measures
Name Time Method