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

Primary Purpose

Colorectal Cancer Metastatic

Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Bevacizumab
Irinotecan
Oxaliplatin
5-fluorouracil/leucovorin
Sponsored by
Gruppo Oncologico del Nord-Ovest
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Colorectal Cancer Metastatic

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    FOLFOXIRI plus bevacizumab

    Arm Description

    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

    Outcomes

    Primary Outcome Measures

    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.

    Secondary Outcome Measures

    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.
    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.
    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).
    Evaluation of potential surrogate markers predictive of bevacizumab activity
    During first-line therapy and at disease progression.

    Full Information

    First Posted
    July 9, 2010
    Last Updated
    March 10, 2015
    Sponsor
    Gruppo Oncologico del Nord-Ovest
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    1. Study Identification

    Unique Protocol Identification Number
    NCT01163396
    Brief Title
    First-line FOLFOXIRI In Combination With Bevacizumab For Metastatic Colorectal Cancer
    Acronym
    FOIB
    Official Title
    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
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    March 2015
    Overall Recruitment Status
    Completed
    Study Start Date
    July 2007 (undefined)
    Primary Completion Date
    April 2009 (Actual)
    Study Completion Date
    April 2010 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Gruppo Oncologico del Nord-Ovest

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Colorectal Cancer Metastatic

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    57 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    FOLFOXIRI plus bevacizumab
    Arm Type
    Experimental
    Arm Description
    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 Type
    Drug
    Intervention Name(s)
    Bevacizumab
    Intervention Type
    Drug
    Intervention Name(s)
    Irinotecan
    Intervention Type
    Drug
    Intervention Name(s)
    Oxaliplatin
    Intervention Type
    Drug
    Intervention Name(s)
    5-fluorouracil/leucovorin
    Primary Outcome Measure Information:
    Title
    Progression-free survival (PFS)
    Description
    PFS was calculated from the day of treatment start to the first observation of disease progression or death from any cause.
    Time Frame
    PFS rate at 10 months from study entry
    Secondary Outcome Measure Information:
    Title
    Response rate (RR)
    Description
    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.
    Time Frame
    2007-2010
    Title
    Overall survival (OS)
    Description
    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.
    Time Frame
    2007-2010
    Title
    Number of Participants with Adverse Events as a Measure of Safety and Tolerability
    Description
    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).
    Time Frame
    2007-2010
    Title
    Evaluation of potential surrogate markers predictive of bevacizumab activity
    Description
    During first-line therapy and at disease progression.
    Time Frame
    2007-2010

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    75 Years
    Accepts Healthy Volunteers
    No
    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
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Alfredo Falcone, MD
    Organizational Affiliation
    University of Pisa
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    27986363
    Citation
    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.
    Results Reference
    derived
    PubMed Identifier
    20702138
    Citation
    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.
    Results Reference
    derived

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

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