First-line FOLFOXIRI In Combination With Bevacizumab For Metastatic Colorectal Cancer
Phase 2
Completed
- Conditions
- Colorectal Cancer Metastatic
- Interventions
- Registration Number
- NCT01163396
- Lead Sponsor
- Gruppo Oncologico del Nord-Ovest
- Brief Summary
This is a single-arm, open-label, multicentre phase II study evaluating the safety and efficacy of the combination of the G.O.N.O. FOLFOXIRI regimen with bevacizumab as first-line treatment of metastatic colorectal cancer.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 57
Inclusion Criteria
- Histologically confirmed colorectal adenocarcinoma
- Unresectable and measurable metastatic disease (RECIST criteria)
- Male or female, aged > 18 years and ≤ 75 years
- ECOG Performance Status (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 109/L; platelets ≥ 100 x 109/L, Hb ≥ 9 g/dL
- INR ≤ 1.5 and aPTT ≤ 1.5 x ULN within 7 days prior to starting study treatment
- 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
- Urine dipstick for proteinuria < 2+. If urine dipstick is ≥ 2+, 24- hour urine must demonstrate ≤ 1 g of protein in 24 hours
- 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 radiotherapy and 4 weeks from surgery
Exclusion Criteria
- Prior palliative chemotherapy
- Prior treatment with bevacizumab
- Bowel obstruction (or subobstruction)
- History of inflammatory enteropathy or extensive intestinal resection (> hemicolectomy or extensive small intestine resection with chronic diarrhea)
- Symptomatic peripheral neuropathy > 2 grade NCIC-CTG criteria
- Presence or history of CNS metastasis
- Active uncontrolled infections
- Active disseminated intravascular coagulation
- Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to treatment, or anticipation of the need for major surgery during the course of the study
- Central Venous Access Device (CVAD) for chemotherapy administration inserted within 2 days prior to study treatment start
- Past or current history of malignancies other than colorectal carcinoma, except for curatively treated basal and squamous cell carcinoma of the skin cancer or in situ carcinoma of the cervix
- Clinically significant 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
- Uncontrolled hypertension
- 24-hour urine protein > 1 g if dipstick > 2+
- History of thromboembolic or hemorrhagic events within 6 months prior to treatment
- Evidence of bleeding diathesis or coagulopathy
- Serious, non healing wound/ulcer or serious bone fracture
- No therapeutic anticoagulation or antiplatelet agents or NSAID with anti-platelet activity (aspirin ≤ 325 mg/day allowed)
- Pregnancy or lactation
- Fertile women (< 2 years after last menstruation) and men of childbearing potential not willing to use effective means of contraception
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description FOLFOXIRI plus bevacizumab Bevacizumab BEVACIZUMAB 5 mg/Kg i.v. followed by IRINOTECAN 165 mg/sqm i.v. over 1 hr followed by OXALIPLATIN 85 mg/sqm i.v. over 2 hr concomitantly with l-LV 200 mg/sqm over 2 hrs followed by 5FU 3.200 mg/sqm c.i. over 48 hrs starting on day 1. Cycles repeated every 2 weeks FOLFOXIRI plus bevacizumab Oxaliplatin BEVACIZUMAB 5 mg/Kg i.v. followed by IRINOTECAN 165 mg/sqm i.v. over 1 hr followed by OXALIPLATIN 85 mg/sqm i.v. over 2 hr concomitantly with l-LV 200 mg/sqm over 2 hrs followed by 5FU 3.200 mg/sqm c.i. over 48 hrs starting on day 1. Cycles repeated every 2 weeks FOLFOXIRI plus bevacizumab Irinotecan BEVACIZUMAB 5 mg/Kg i.v. followed by IRINOTECAN 165 mg/sqm i.v. over 1 hr followed by OXALIPLATIN 85 mg/sqm i.v. over 2 hr concomitantly with l-LV 200 mg/sqm over 2 hrs followed by 5FU 3.200 mg/sqm c.i. over 48 hrs starting on day 1. Cycles repeated every 2 weeks FOLFOXIRI plus bevacizumab 5-fluorouracil/leucovorin BEVACIZUMAB 5 mg/Kg i.v. followed by IRINOTECAN 165 mg/sqm i.v. over 1 hr followed by OXALIPLATIN 85 mg/sqm i.v. over 2 hr concomitantly with l-LV 200 mg/sqm over 2 hrs followed by 5FU 3.200 mg/sqm c.i. over 48 hrs starting on day 1. Cycles repeated every 2 weeks
- Primary Outcome Measures
Name Time Method Progression-free survival (PFS) PFS rate at 10 months from study entry PFS was calculated from the day of treatment start to the first observation of disease progression or death from any cause.
- Secondary Outcome Measures
Name Time Method Response rate (RR) 2007-2010 Response evaluation was performed every 8 weeks from the day of treatment start until disease progression for each enrolled patient for the full lenght of the study. Response evaluation was performed according to RECIST criteria. Responses were subsequently confirmed by a central review.
Overall survival (OS) 2007-2010 OS was calculated from the day of treatment start until death from any cause for each enrolled patient for the full lenght of the study, censoring patients who had not died at the last date known to be alive.
Number of Participants with Adverse Events as a Measure of Safety and Tolerability 2007-2010 During the full lenght of first-line treatment, number of enrolled patients reporting adverse events was recorded. Adverse events were evaluated according to National Cancer Institute Common Toxicity Criteria (version 3.0).
Evaluation of potential surrogate markers predictive of bevacizumab activity 2007-2010 During first-line therapy and at disease progression.