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

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

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.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer Metastatic
• Intervention / Treatment: Drug: Oxaliplatin; Drug: Bevacizumab; Drug: Irinotecan; Drug: 5-fluorouracil/leucovorin

• Study Type: Interventional
• Enrollment (Actual): 57
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 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	Drug: Oxaliplatin; Drug: Bevacizumab; Drug: Irinotecan; Drug: 5-fluorouracil/leucovorin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	PFS was calculated from the day of treatment start to the first observation of disease progression or death from any cause.	PFS rate at 10 months from study entry

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rate (RR)	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.	2007-2010
Overall survival (OS)	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.	2007-2010
Number of Participants with Adverse Events as a Measure of Safety and Tolerability	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).	2007-2010
Evaluation of potential surrogate markers predictive of bevacizumab activity	During first-line therapy and at disease progression.	2007-2010

Collaborators and Investigators

• Sponsor: Gruppo Oncologico del Nord-Ovest

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: July 1, 2007
• Primary Completion (ACTUAL): April 1, 2009
• Study Completion (ACTUAL): April 1, 2010

Study Registration Dates

• First Submitted: July 9, 2010
• First Submitted That Met QC Criteria: July 14, 2010
• First Posted (ESTIMATE): July 15, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): March 11, 2015
• Last Update Submitted That Met QC Criteria: March 10, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Micronutrients; Vitamins; Topoisomerase I Inhibitors; Antidotes; Vitamin B Complex; Fluorouracil; Oxaliplatin; Bevacizumab; Leucovorin; Irinotecan
• Other Study ID Numbers: ASL606LIOM01