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
About this trial
This is an interventional treatment trial for Colorectal Cancer Metastatic
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
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
NCT ID
NCT01163396
First Posted
July 9, 2010
Last Updated
March 10, 2015
Sponsor
Gruppo Oncologico del Nord-Ovest
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
Learn more about this trial
First-line FOLFOXIRI In Combination With Bevacizumab For Metastatic Colorectal Cancer
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