Back to resultsA Study of Avastin (Bevacizumab) With XELOX or FOLFOX in Patients With Metastatic Colorectal Cancer and Disease Progression Under First-line FOLFIRI and Avastin
Primary Purpose
Colorectal Cancer
Status
Completed
Phase
Phase 2
Locations
Belgium
Study Type
Interventional
Intervention
fluorouracil (5FU)
leucovorin
bevacizumab [Avastin]
capecitabine [Xeloda]
oxaliplatin
Sponsored by
About this trial
This is an interventional treatment trial for Colorectal Cancer
Eligibility Criteria
Inclusion Criteria:
- adult patients >/=18 years of age
- metastatic colorectal cancer
- at least 1 measurable lesion according to RECIST v. 1.1
- patients with disease progression with prior FOLFIRI + Avastin therapy who are not candidates for primary metastasectomy
- disease progression </= 8 weeks after last dose of Avastin
- ECOG </=2
- No more than 8 weeks between 1st-line treatment with FOLFIRI + Avastin and 2nd-line treatment with XELOX or FOLFOX + Avastin
Exclusion Criteria:
- disease progression > 8 weeks after last Avastin administration
- clinically significant cardiovascular disease
- CNS disease except for treated brain metastasis
- history of other malignancies within 2 years prior to start of study treatment (with the exception of curatively treated basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix)
- major surgery, open biopsy, or significant traumatic injury within 28 days prior to start of study treatment
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Avastin (bevacizumab) + standard of care
Arm Description
Outcomes
Primary Outcome Measures
Progression-Free Survival (PFS) From the Start of Treatment Beyond Progression
PFS from the start of treatment beyond progression was defined as the interval between the start of beyond-progression therapy and the date at which disease progression was documented. Progression of disease was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1 and abdominal/pelvic computerized tomography (CT) or magnetic resonance imaging (MRI) scanning as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. The same method of assessment and the same technique were to be used to evaluate each lesion throughout the entire study. If more than one method was used, data from the most accurate method according to RECIST were recorded. Median PFS was estimated using the Kaplan-Meier method.
Secondary Outcome Measures
PFS From the Start of First-Line Therapy
PFS from the start of first-line therapy was defined as the interval between the start of first-line therapy and the date at which second disease progression (after the start of beyond progression therapy) was documented. Progression of disease was evaluated using RECIST version 1.1 and abdominal/pelvic CT or MRI scanning. The same method of assessment and the same technique were to be used to evaluate each lesion throughout the entire study. If more than one method was used, data from the most accurate method according to RECIST were recorded. Median PFS was estimated using the Kaplan-Meier method.
Percentage of Participants With an Overall Response of Complete Response (CR) or Partial Response (PR)
Percentage of participants with an overall response of CR or PR according to RECIST criteria.
CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must have decreased to normal (short axis less than [<]10 millimeters [mm]). No new lesions. PR was defined as greater than or equal to (≥)30 percent (%) decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions.
Geometric Mean Values of Pro-Angiogenic Cytokine Concentrations at Baseline and Prior to Progression
Pro-angiogenic cytokine concentrations of placental growth factor (PlGF), basic fibroblast growth factor (bFGF), and hepatocyte growth factor (HGF) in participant sera were measured and reported in units of picograms/milliliter (pg/mL). The geometric mean was calculated as exp10 (mean of log10 transformed concentration) and the standard deviation (SD) is SD of log10 transformed concentration.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01077739
Brief Title
A Study of Avastin (Bevacizumab) With XELOX or FOLFOX in Patients With Metastatic Colorectal Cancer and Disease Progression Under First-line FOLFIRI and Avastin
Official Title
A Single-arm Open-label Phase II Study: Treatment Beyond Progression by Adding Bevacizumab to XELOX or FOLFOX Chemotherapy in Patients With Metastatic Colorectal Cancer and Disease Progression Under First-line FOLFIRI + Bevacizumab Combination
Study Type
Interventional
2. Study Status
Record Verification Date
December 2014
Overall Recruitment Status
Completed
Study Start Date
July 2009 (undefined)
Primary Completion Date
January 2012 (Actual)
Study Completion Date
January 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
4. Oversight
5. Study Description
Brief Summary
This open-label single arm study will evaluate the efficacy and safety of Avastin added to XELOX or FOLFOX in patients with metastatic colorectal cancer and disease progression on 1st line therapy with FOLFIRI plus Avastin. Patients will receive either Avastin (7.5mg/kg iv infusion every 3 weeks) and standard XELOX (Xeloda [capecitabine] plus oxaliplatin) chemotherapy or Avastin (5 mg/kg iv infusion every 2 weeks) and standard FOLFOX (5-FU and leucovorin plus oxaliplatin) chemotherapy. The anticipated time on study treatment is until disease progression, and the target sample size is 100 individuals.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
75 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Avastin (bevacizumab) + standard of care
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
fluorouracil (5FU)
Intervention Description
standard FOLFOX regimen
Intervention Type
Drug
Intervention Name(s)
leucovorin
Intervention Description
standard FOLFOX regimen
Intervention Type
Drug
Intervention Name(s)
bevacizumab [Avastin]
Intervention Description
7.5 mg/kg iv infusion every 3 weeks OR 5 mg/kg iv infusion every 2 weeks
Intervention Type
Drug
Intervention Name(s)
capecitabine [Xeloda]
Intervention Description
standard XELOX regimen
Intervention Type
Drug
Intervention Name(s)
oxaliplatin
Intervention Description
standard XELOX or FOLFOX regimen
Primary Outcome Measure Information:
Title
Progression-Free Survival (PFS) From the Start of Treatment Beyond Progression
Description
PFS from the start of treatment beyond progression was defined as the interval between the start of beyond-progression therapy and the date at which disease progression was documented. Progression of disease was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1 and abdominal/pelvic computerized tomography (CT) or magnetic resonance imaging (MRI) scanning as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. The same method of assessment and the same technique were to be used to evaluate each lesion throughout the entire study. If more than one method was used, data from the most accurate method according to RECIST were recorded. Median PFS was estimated using the Kaplan-Meier method.
Time Frame
Baseline, every 9 weeks until disease progression, at end of treatment or withdrawal, for up to 24 months
Secondary Outcome Measure Information:
Title
PFS From the Start of First-Line Therapy
Description
PFS from the start of first-line therapy was defined as the interval between the start of first-line therapy and the date at which second disease progression (after the start of beyond progression therapy) was documented. Progression of disease was evaluated using RECIST version 1.1 and abdominal/pelvic CT or MRI scanning. The same method of assessment and the same technique were to be used to evaluate each lesion throughout the entire study. If more than one method was used, data from the most accurate method according to RECIST were recorded. Median PFS was estimated using the Kaplan-Meier method.
Time Frame
Baseline, every 9 weeks until disease progression, at end of treatment or withdrawal, for up to 24 months
Title
Percentage of Participants With an Overall Response of Complete Response (CR) or Partial Response (PR)
Description
Percentage of participants with an overall response of CR or PR according to RECIST criteria.
CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must have decreased to normal (short axis less than [<]10 millimeters [mm]). No new lesions. PR was defined as greater than or equal to (≥)30 percent (%) decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions.
Time Frame
Baseline, every 9 weeks until disease progression, at end of treatment or withdrawal, for up to 24 months
Title
Geometric Mean Values of Pro-Angiogenic Cytokine Concentrations at Baseline and Prior to Progression
Description
Pro-angiogenic cytokine concentrations of placental growth factor (PlGF), basic fibroblast growth factor (bFGF), and hepatocyte growth factor (HGF) in participant sera were measured and reported in units of picograms/milliliter (pg/mL). The geometric mean was calculated as exp10 (mean of log10 transformed concentration) and the standard deviation (SD) is SD of log10 transformed concentration.
Time Frame
Baseline, every 9 weeks until disease progression, at final visit or at withdrawal, for up to 24 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
adult patients >/=18 years of age
metastatic colorectal cancer
at least 1 measurable lesion according to RECIST v. 1.1
patients with disease progression with prior FOLFIRI + Avastin therapy who are not candidates for primary metastasectomy
disease progression </= 8 weeks after last dose of Avastin
ECOG </=2
No more than 8 weeks between 1st-line treatment with FOLFIRI + Avastin and 2nd-line treatment with XELOX or FOLFOX + Avastin
Exclusion Criteria:
disease progression > 8 weeks after last Avastin administration
clinically significant cardiovascular disease
CNS disease except for treated brain metastasis
history of other malignancies within 2 years prior to start of study treatment (with the exception of curatively treated basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix)
major surgery, open biopsy, or significant traumatic injury within 28 days prior to start of study treatment
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
City
Aalst
ZIP/Postal Code
9300
Country
Belgium
City
Arlon
ZIP/Postal Code
6700
Country
Belgium
City
Assebroek
ZIP/Postal Code
8310
Country
Belgium
City
AYE
ZIP/Postal Code
6900
Country
Belgium
City
Bonheiden
ZIP/Postal Code
2820
Country
Belgium
City
Brasschaat
ZIP/Postal Code
2930
Country
Belgium
City
Brugge
ZIP/Postal Code
8000
Country
Belgium
City
Bruxelles
ZIP/Postal Code
1020
Country
Belgium
City
Bruxelles
ZIP/Postal Code
1180
Country
Belgium
City
Bruxelles
ZIP/Postal Code
1200
Country
Belgium
City
Charleroi
ZIP/Postal Code
6000
Country
Belgium
City
Dendermonde
ZIP/Postal Code
9200
Country
Belgium
City
Edegem
ZIP/Postal Code
2650
Country
Belgium
City
Genk
ZIP/Postal Code
3600
Country
Belgium
City
Gent
ZIP/Postal Code
9000
Country
Belgium
City
Hasselt
ZIP/Postal Code
3500
Country
Belgium
City
Kortrijk
ZIP/Postal Code
8500
Country
Belgium
City
Mechelen
ZIP/Postal Code
2800
Country
Belgium
City
Merksem
ZIP/Postal Code
2170
Country
Belgium
City
Mont-godinne
ZIP/Postal Code
5530
Country
Belgium
City
Montigny-le-Tilleul
ZIP/Postal Code
6110
Country
Belgium
City
Namur
ZIP/Postal Code
5000
Country
Belgium
City
Oostende
ZIP/Postal Code
8400
Country
Belgium
City
Sint-Niklaas
ZIP/Postal Code
9100
Country
Belgium
City
Tournai
ZIP/Postal Code
7500
Country
Belgium
City
Turnhout
ZIP/Postal Code
2300
Country
Belgium
City
Verviers
ZIP/Postal Code
4800
Country
Belgium
City
Wilrijk
ZIP/Postal Code
2610
Country
Belgium
12. IPD Sharing Statement
Learn more about this trial
A Study of Avastin (Bevacizumab) With XELOX or FOLFOX in Patients With Metastatic Colorectal Cancer and Disease Progression Under First-line FOLFIRI and Avastin
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