Back to resultsA Study of Avastin (Bevacizumab) in Combination Chemotherapy in Patients With Metastatic Cancer of the Colon or Rectum
Primary Purpose
Colorectal Cancer
Status
Completed
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
Bevacizumab [Avastin]
Capecitabine
Irinotecan
Sponsored by
About this trial
This is an interventional treatment trial for Colorectal Cancer
Eligibility Criteria
Inclusion Criteria:
- adult patients >=18 years of age;
- colon or rectal cancer, with metastases;
- >=1 measurable lesion.
Exclusion Criteria:
- previous systemic treatment for advanced disease;
- radiotherapy to any site within 4 weeks before study;
- daily aspirin (>325 mg/day), anticoagulants, or other medications known to predispose to gastrointestinal ulceration;
- co-existing malignancies or malignancies diagnosed within last 5 years (except basal cell cancer or cervical cancer in situ).
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Bevacizumab + Irinotecan + Capecitabine (1000 mg/m^2)
Bevacizumab + Capecitabine (1250 mg/m^2)
Bevacizumab + Capecitabine (650 mg/m^2)
Arm Description
Bevacizumab was administered as a 7.5 mg/kg intravenous infusion over 30 to 90 minutes on Day 1 of each 3 week cycle. Irinotecan was administered as a 240 mg/m^2 intravenous infusion over 60 minutes (Day 1) every 3 weeks. Capecitabine was administered orally at a dose of 1000 mg/m^2 twice daily (Day 2 to 15). Cycle length was 3 weeks consisting of 2 weeks of capecitabine treatment followed by 1 week without treatment up to 6 cycles. After 6 cycles, participants with objective response or SD were treated with bevacizumab alone until unacceptable toxicity, PD, or participant withdrawal.
Bevacizumab was administered as a 7.5 mg/kg intravenous infusion over 30 to 90 minutes on Day 1 of each 3 week cycle in combination with capecitabine administered orally at 1250 mg/m^2 twice daily (Day 1 to 14). Cycle length was 3 weeks with 2 weeks of capecitabine treatment followed by 1 week without treatment up to 6 cycles. After 6 cycles, participants with objective response or SD were treated with bevacizumab alone until unacceptable toxicity, PD, or participant withdrawal.
Bevacizumab was administered as a 7.5 mg/kg intravenous infusion over 30 to 90 minutes on Day 1 of each 3 Week cycle in combination with capecitabine administered orally at 650 mg/m^2 twice daily (Day 1 to 21). Cycle length was 3 weeks with 3 weeks of capecitabine treatment without interruptions. Participants received the same regimen until unacceptable toxicity, PD, or participant withdrawal.
Outcomes
Primary Outcome Measures
Percentage of Participants With Disease Progression or Death
Disease progression was defined according to National Cancer Institute (NCI) guidelines and best clinical practices.
Time to Progression (TTP)
TTP is defined as the time from date of randomization until objective tumor progression or death due to any cause. It includes deaths and thus can be correlated to overall survival.
Secondary Outcome Measures
Percentage of Participants Who Died
Overall survival is defined as the time from date of randomization until death from any cause
Overall Survival
Overall survival is defined as the time from date of randomization until death from any cause; Kaplan-Meier estimates were used for analysis.
Percentage of Participants With Treatment Failure
Treatment failure is defined as discontinuation of treatment for any reason, including disease progression, death, treatment toxicity, insufficient therapeutic response, failure to return, refusing treatment, being unwilling to cooperate and withdrawing consent.
Time to Treatment Failure
Time to treatment failure is defined as a composite endpoint measuring time from date of randomization to discontinuation of treatment for any reason, including disease progression, death, treatment toxicity, insufficient therapeutic response, failure to return, refusing treatment, being unwilling to cooperate and withdrawing consent. Analysis was performed using Kaplan-Meier estimates.
Percentage of Participants With Progression Excluding Deaths
The failure event was defined as tumor progression excluding deaths due to any reason.
Time to Progression Excluding Deaths
The failure event was defined as tumor progression excluding deaths due to any reason. Kaplan-Meier estimates were used for analysis.
Percentage of Participants With Progression Excluding Deaths Not Related to Underlying Cancer
The failure event was defined as tumor progression excluding only deaths not related to underlying cancer.
Time to Progression Excluding Deaths Not Related to Underlying Cancer
The failure event was defined as tumor progression excluding only deaths not related to underlying cancer. Kaplan-Meier estimates were used for analysis.
Percentage of Participants by Best Overall Response
Best overall response is defined as the best response recorded from the date of randomization until disease progression or recurrence. Complete response (CR): at least 2 determinations of CR at least 4 weeks apart before progression; Partial response (PR): at least 2 determinations of PR at least 4 weeks apart before progression; Stable disease (SD): at least one SD assessment; Progressive Disease (PD): Disease progression or death due to underlying cancer. CR: Complete disappearance of all target lesions; PR: At least 30% decrease in the sum of the longest diameter of all target lesions taking as reference the baseline sum of all target lesions; PD: At least 20% decrease in the sum of the longest diameter of all target lesions taking as reference the baseline sum of longest diameter of all target lesions or the appearance of one or more new lesions; SD: Neither sufficient shrinkage to qualify for CR or PR or increase in lesions;
Percentage of Participants With a Best Overall Response of CR or PR
CR: Complete disappearance of all target lesions; PR: At least 30% decrease in the sum of the longest diameter of all target lesions taking as reference the baseline sum of all target lesions;
Percentage of Participants With Stable Disease
Stable disease rate was the proportion of participants who achieved CR, PR, or SD.
Percentage of Participants With Progressive Disease Within 12 Weeks From Start of Treatment
Early progression was the proportion of participants with progressive disease within 12 weeks from the start of treatment.
Duration of Overall Response
Duration of overall response included participants who achieved a CR or PR.
Duration of Stable Disease (SD)
Duration of SD was calculated as the number of months the participants remained in CR, PR or SD. Kaplan-Meier estimates were used for analysis.
Duration of Overall Complete Response
Duration of complete response was calculated as the time in months from the date of randomization to the date of first documentation of CR. Kaplan-Meier estimates were used for analysis.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01131078
Brief Title
A Study of Avastin (Bevacizumab) in Combination Chemotherapy in Patients With Metastatic Cancer of the Colon or Rectum
Official Title
A Randomized, Open-label Study Comparing the Effect of 3 Chemotherapy Regimens Containing Avastin on Time to Disease Progression in Patients With Metastatic Colorectal Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
June 2015
Overall Recruitment Status
Completed
Study Start Date
June 2005 (undefined)
Primary Completion Date
November 2012 (Actual)
Study Completion Date
November 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
A study of Avastin (bevacizumab) in combination chemotherapy in patients with metastatic cancer of the colon or rectum. The anticipated time on study treatment is until disease progression.
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
Randomized
Enrollment
306 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Bevacizumab + Irinotecan + Capecitabine (1000 mg/m^2)
Arm Type
Experimental
Arm Description
Bevacizumab was administered as a 7.5 mg/kg intravenous infusion over 30 to 90 minutes on Day 1 of each 3 week cycle. Irinotecan was administered as a 240 mg/m^2 intravenous infusion over 60 minutes (Day 1) every 3 weeks. Capecitabine was administered orally at a dose of 1000 mg/m^2 twice daily (Day 2 to 15). Cycle length was 3 weeks consisting of 2 weeks of capecitabine treatment followed by 1 week without treatment up to 6 cycles. After 6 cycles, participants with objective response or SD were treated with bevacizumab alone until unacceptable toxicity, PD, or participant withdrawal.
Arm Title
Bevacizumab + Capecitabine (1250 mg/m^2)
Arm Type
Experimental
Arm Description
Bevacizumab was administered as a 7.5 mg/kg intravenous infusion over 30 to 90 minutes on Day 1 of each 3 week cycle in combination with capecitabine administered orally at 1250 mg/m^2 twice daily (Day 1 to 14). Cycle length was 3 weeks with 2 weeks of capecitabine treatment followed by 1 week without treatment up to 6 cycles. After 6 cycles, participants with objective response or SD were treated with bevacizumab alone until unacceptable toxicity, PD, or participant withdrawal.
Arm Title
Bevacizumab + Capecitabine (650 mg/m^2)
Arm Type
Experimental
Arm Description
Bevacizumab was administered as a 7.5 mg/kg intravenous infusion over 30 to 90 minutes on Day 1 of each 3 Week cycle in combination with capecitabine administered orally at 650 mg/m^2 twice daily (Day 1 to 21). Cycle length was 3 weeks with 3 weeks of capecitabine treatment without interruptions. Participants received the same regimen until unacceptable toxicity, PD, or participant withdrawal.
Intervention Type
Drug
Intervention Name(s)
Bevacizumab [Avastin]
Other Intervention Name(s)
Avastin
Intervention Description
Bevacizumab was administered as a 7.5 mg/kg intravenous infusion over 30 to 90 minutes on Day 1 of each 3 week cycle.
Intervention Type
Drug
Intervention Name(s)
Capecitabine
Intervention Description
Capecitabine was administered orally at a doses of 1000 or 1250, mg/m^2 twice daily (Day 2 to 15) or as 650 mg/m^2 twice daily on Days 1 to 21.
Intervention Type
Drug
Intervention Name(s)
Irinotecan
Intervention Description
Irinotecan was administered as a 240 mg/m^2 intravenous infusion over 60 minutes (Day 1) every 3 weeks.
Primary Outcome Measure Information:
Title
Percentage of Participants With Disease Progression or Death
Description
Disease progression was defined according to National Cancer Institute (NCI) guidelines and best clinical practices.
Time Frame
Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death
Title
Time to Progression (TTP)
Description
TTP is defined as the time from date of randomization until objective tumor progression or death due to any cause. It includes deaths and thus can be correlated to overall survival.
Time Frame
Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death
Secondary Outcome Measure Information:
Title
Percentage of Participants Who Died
Description
Overall survival is defined as the time from date of randomization until death from any cause
Time Frame
Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death
Title
Overall Survival
Description
Overall survival is defined as the time from date of randomization until death from any cause; Kaplan-Meier estimates were used for analysis.
Time Frame
Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death
Title
Percentage of Participants With Treatment Failure
Description
Treatment failure is defined as discontinuation of treatment for any reason, including disease progression, death, treatment toxicity, insufficient therapeutic response, failure to return, refusing treatment, being unwilling to cooperate and withdrawing consent.
Time Frame
Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death
Title
Time to Treatment Failure
Description
Time to treatment failure is defined as a composite endpoint measuring time from date of randomization to discontinuation of treatment for any reason, including disease progression, death, treatment toxicity, insufficient therapeutic response, failure to return, refusing treatment, being unwilling to cooperate and withdrawing consent. Analysis was performed using Kaplan-Meier estimates.
Time Frame
Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death
Title
Percentage of Participants With Progression Excluding Deaths
Description
The failure event was defined as tumor progression excluding deaths due to any reason.
Time Frame
Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death
Title
Time to Progression Excluding Deaths
Description
The failure event was defined as tumor progression excluding deaths due to any reason. Kaplan-Meier estimates were used for analysis.
Time Frame
Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death
Title
Percentage of Participants With Progression Excluding Deaths Not Related to Underlying Cancer
Description
The failure event was defined as tumor progression excluding only deaths not related to underlying cancer.
Time Frame
Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death
Title
Time to Progression Excluding Deaths Not Related to Underlying Cancer
Description
The failure event was defined as tumor progression excluding only deaths not related to underlying cancer. Kaplan-Meier estimates were used for analysis.
Time Frame
Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death
Title
Percentage of Participants by Best Overall Response
Description
Best overall response is defined as the best response recorded from the date of randomization until disease progression or recurrence. Complete response (CR): at least 2 determinations of CR at least 4 weeks apart before progression; Partial response (PR): at least 2 determinations of PR at least 4 weeks apart before progression; Stable disease (SD): at least one SD assessment; Progressive Disease (PD): Disease progression or death due to underlying cancer. CR: Complete disappearance of all target lesions; PR: At least 30% decrease in the sum of the longest diameter of all target lesions taking as reference the baseline sum of all target lesions; PD: At least 20% decrease in the sum of the longest diameter of all target lesions taking as reference the baseline sum of longest diameter of all target lesions or the appearance of one or more new lesions; SD: Neither sufficient shrinkage to qualify for CR or PR or increase in lesions;
Time Frame
Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death
Title
Percentage of Participants With a Best Overall Response of CR or PR
Description
CR: Complete disappearance of all target lesions; PR: At least 30% decrease in the sum of the longest diameter of all target lesions taking as reference the baseline sum of all target lesions;
Time Frame
Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death
Title
Percentage of Participants With Stable Disease
Description
Stable disease rate was the proportion of participants who achieved CR, PR, or SD.
Time Frame
Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death
Title
Percentage of Participants With Progressive Disease Within 12 Weeks From Start of Treatment
Description
Early progression was the proportion of participants with progressive disease within 12 weeks from the start of treatment.
Time Frame
Randomization, Weeks 3, 6 and 9, and 12
Title
Duration of Overall Response
Description
Duration of overall response included participants who achieved a CR or PR.
Time Frame
Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death
Title
Duration of Stable Disease (SD)
Description
Duration of SD was calculated as the number of months the participants remained in CR, PR or SD. Kaplan-Meier estimates were used for analysis.
Time Frame
Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death
Title
Duration of Overall Complete Response
Description
Duration of complete response was calculated as the time in months from the date of randomization to the date of first documentation of CR. Kaplan-Meier estimates were used for analysis.
Time Frame
Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years
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;
colon or rectal cancer, with metastases;
>=1 measurable lesion.
Exclusion Criteria:
previous systemic treatment for advanced disease;
radiotherapy to any site within 4 weeks before study;
daily aspirin (>325 mg/day), anticoagulants, or other medications known to predispose to gastrointestinal ulceration;
co-existing malignancies or malignancies diagnosed within last 5 years (except basal cell cancer or cervical cancer in situ).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Chair
Facility Information:
City
Paola
State/Province
Calabria
ZIP/Postal Code
87027
Country
Italy
City
Benevento
State/Province
Campania
ZIP/Postal Code
82100
Country
Italy
City
Napoli
State/Province
Campania
ZIP/Postal Code
80136
Country
Italy
City
Bologna
State/Province
Emilia-Romagna
ZIP/Postal Code
40138
Country
Italy
City
Carpi
State/Province
Emilia-Romagna
ZIP/Postal Code
41012
Country
Italy
City
Piacenza
State/Province
Emilia-Romagna
ZIP/Postal Code
29100
Country
Italy
City
Latisana
State/Province
Friuli-Venezia Giulia
ZIP/Postal Code
33053
Country
Italy
City
Udine
State/Province
Friuli-Venezia Giulia
ZIP/Postal Code
33100
Country
Italy
City
Latina
State/Province
Lazio
ZIP/Postal Code
04100
Country
Italy
City
Roma
State/Province
Lazio
ZIP/Postal Code
00168
Country
Italy
City
Roma
State/Province
Lazio
ZIP/Postal Code
00186
Country
Italy
City
Brescia
State/Province
Lombardia
ZIP/Postal Code
25123
Country
Italy
City
Busto Arsizio
State/Province
Lombardia
ZIP/Postal Code
21052
Country
Italy
City
Casalpusterlengo
State/Province
Lombardia
ZIP/Postal Code
20071
Country
Italy
City
Cremona
State/Province
Lombardia
ZIP/Postal Code
26100
Country
Italy
City
Gorgonzola
State/Province
Lombardia
ZIP/Postal Code
20064
Country
Italy
City
Lecco
State/Province
Lombardia
ZIP/Postal Code
23900
Country
Italy
City
Legnago
State/Province
Lombardia
ZIP/Postal Code
37045
Country
Italy
City
Mantova
State/Province
Lombardia
ZIP/Postal Code
46100
Country
Italy
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20121
Country
Italy
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20133
Country
Italy
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20142
Country
Italy
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20162
Country
Italy
City
Pavia
State/Province
Lombardia
ZIP/Postal Code
27100
Country
Italy
City
Saronno
State/Province
Lombardia
ZIP/Postal Code
21047
Country
Italy
City
Sondrio
State/Province
Lombardia
ZIP/Postal Code
23100
Country
Italy
City
Treviglio
State/Province
Lombardia
ZIP/Postal Code
24047
Country
Italy
City
Varese
State/Province
Lombardia
ZIP/Postal Code
21100
Country
Italy
City
Ancona
State/Province
Marche
ZIP/Postal Code
60121
Country
Italy
City
Novara
State/Province
Piemonte
ZIP/Postal Code
28100
Country
Italy
City
Torino
State/Province
Piemonte
ZIP/Postal Code
10153
Country
Italy
City
Cagliari
State/Province
Sardegna
ZIP/Postal Code
09100
Country
Italy
City
Catania
State/Province
Sicilia
ZIP/Postal Code
95100
Country
Italy
City
Palermo
State/Province
Sicilia
ZIP/Postal Code
90127
Country
Italy
City
Firenze
State/Province
Toscana
ZIP/Postal Code
50139
Country
Italy
City
Grosseto
State/Province
Toscana
ZIP/Postal Code
58100
Country
Italy
City
Pisa
State/Province
Toscana
ZIP/Postal Code
56100
Country
Italy
City
Prato
State/Province
Toscana
ZIP/Postal Code
59100
Country
Italy
City
Bolzano
State/Province
Trentino-Alto Adige
ZIP/Postal Code
39100
Country
Italy
City
Terni
State/Province
Umbria
ZIP/Postal Code
05100
Country
Italy
City
Camposampiero
State/Province
Veneto
ZIP/Postal Code
35012
Country
Italy
City
Este
State/Province
Veneto
ZIP/Postal Code
35042
Country
Italy
City
Montecchio Maggiore
State/Province
Veneto
ZIP/Postal Code
36075
Country
Italy
City
Negrar
State/Province
Veneto
ZIP/Postal Code
37024
Country
Italy
12. IPD Sharing Statement
Learn more about this trial
A Study of Avastin (Bevacizumab) in Combination Chemotherapy in Patients With Metastatic Cancer of the Colon or Rectum
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