Open-label, Multicenter, Phase II Study Of First-line Biweekly Irinotecan, Oxaliplatin And Infusional 5-FU/LV (FOLFOXIRI) In Combination With Bevacizumab In Patients With Metastatic Colorectal Cancer
Overview
- Phase
- Phase 2
- Intervention
- Bevacizumab
- Conditions
- Colorectal Cancer Metastatic
- Sponsor
- Gruppo Oncologico del Nord-Ovest
- Enrollment
- 57
- Primary Endpoint
- Progression-free survival (PFS)
- Status
- Completed
- Last Updated
- 11 years ago
Overview
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.
Investigators
Eligibility Criteria
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
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
Arms & Interventions
FOLFOXIRI plus 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
Intervention: Bevacizumab
FOLFOXIRI plus 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
Intervention: Irinotecan
FOLFOXIRI plus 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
Intervention: Oxaliplatin
FOLFOXIRI plus 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
Intervention: 5-fluorouracil/leucovorin
Outcomes
Primary Outcomes
Progression-free survival (PFS)
Time Frame: 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 Outcomes
- Response rate (RR)(2007-2010)
- Overall survival (OS)(2007-2010)
- Number of Participants with Adverse Events as a Measure of Safety and Tolerability(2007-2010)
- Evaluation of potential surrogate markers predictive of bevacizumab activity(2007-2010)