First-line FOLFOXIRI In Combination With Bevacizumab For Metastatic Colorectal Cancer

• Status: Completed
• Trial end date: 2010-04-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Gruppo Oncologico del Nord-Ovest
• Treatments: Bevacizumab; Fluorouracil; Irinotecan; Leucovorin; Oxaliplatin

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

• 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