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

NCT ID: NCT01163396

Last Updated: 2015-03-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 57 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-07-31
• Study Completion Date: 2010-04-30

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.

Conditions

Colorectal Cancer Metastatic

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Bevacizumab

Intervention Type: DRUG

Irinotecan

Intervention Type: DRUG

Oxaliplatin

Intervention Type: DRUG

5-fluorouracil/leucovorin

Intervention Type: DRUG

Interventions

Bevacizumab

Intervention Type: DRUG

Irinotecan

Intervention Type: DRUG

Oxaliplatin

Intervention Type: DRUG

5-fluorouracil/leucovorin

Intervention Type: DRUG

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
• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gruppo Oncologico del Nord-Ovest

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alfredo Falcone, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pisa

References

Cremolini C, Casagrande M, Loupakis F, Aprile G, Bergamo F, Masi G, Moretto R R, Pietrantonio F, Marmorino F, Zucchelli G, Tomasello G, Tonini G, Allegrini G, Granetto C, Ferrari L, Urbani L, Cillo U, Pilati P, Sensi E, Pellegrinelli A, Milione M, Fontanini G, Falcone A. Efficacy of FOLFOXIRI plus bevacizumab in liver-limited metastatic colorectal cancer: A pooled analysis of clinical studies by Gruppo Oncologico del Nord Ovest. Eur J Cancer. 2017 Mar;73:74-84. doi: 10.1016/j.ejca.2016.10.028. Epub 2016 Dec 13.

Reference Type: DERIVED

PMID: 27986363 (View on PubMed)

Masi G, Loupakis F, Salvatore L, Fornaro L, Cremolini C, Cupini S, Ciarlo A, Del Monte F, Cortesi E, Amoroso D, Granetto C, Fontanini G, Sensi E, Lupi C, Andreuccetti M, Falcone A. Bevacizumab with FOLFOXIRI (irinotecan, oxaliplatin, fluorouracil, and folinate) as first-line treatment for metastatic colorectal cancer: a phase 2 trial. Lancet Oncol. 2010 Sep;11(9):845-52. doi: 10.1016/S1470-2045(10)70175-3. Epub 2010 Aug 9.

Reference Type: DERIVED

PMID: 20702138 (View on PubMed)

Other Identifiers

ASL606LIOM01

Identifier Type: -

Identifier Source: org_study_id