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

NCT01163396 | Completed Phase 2 DMC

• 1 other identifier: ASL606LIOM01
• Study Type: interventional
• Target: 57
• Locations: 0 countries
• Sites: N/A

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• 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

Study Arms (1)

FOLFOXIRI plus bevacizumab

EXPERIMENTAL

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: Bevacizumab; Drug: Irinotecan; Drug: Oxaliplatin; Drug: 5-fluorouracil/leucovorin

Interventions

Bevacizumab DRUG

FOLFOXIRI plus bevacizumab

Irinotecan DRUG

FOLFOXIRI plus bevacizumab

Oxaliplatin DRUG

FOLFOXIRI plus bevacizumab

5-fluorouracil/leucovorin DRUG

FOLFOXIRI plus bevacizumab

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• hour urine protein \> 1 g if dipstick \> 2+
• History of thromboembolic or hemorrhagic events within 6 months prior to treatment

Sponsors & Collaborators

• Gruppo Oncologico del Nord-Ovest: lead

Related Publications (2)

• 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.

  PMID: 27986363 DERIVED

• 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.

  PMID: 20702138 DERIVED

MeSH Terms

Interventions

Bevacizumab; Irinotecan; Oxaliplatin; Fluorouracil; Leucovorin

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Camptothecin; Alkaloids; Heterocyclic Compounds; Coordination Complexes; Organic Chemicals; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes

Study Officials

• Alfredo Falcone, MD

  University of Pisa

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 9, 2010
• First Posted: July 15, 2010
• Study Start: July 1, 2007
• Primary Completion: April 1, 2009
• Study Completion: April 1, 2010
• Last Updated: March 11, 2015

Record last verified: 2015-03