A Study of Avastin (Bevacizumab) in Combination Chemother... | NCT01131078

Label	Type	Description	Intervention Names
Bevacizumab + Irinotecan + Capecitabine (1000 mg/m^2)	Experimental	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.	Drug: Bevacizumab [Avastin] Drug: Capecitabine Drug: Irinotecan
Bevacizumab + Capecitabine (1250 mg/m^2)	Experimental	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.	Drug: Bevacizumab [Avastin] Drug: Capecitabine
Bevacizumab + Capecitabine (650 mg/m^2)	Experimental	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.

Name	Type	Description	Arm Group Labels	Other Names
Bevacizumab [Avastin]	Drug	Bevacizumab was administered as a 7.5 mg/kg intravenous infusion over 30 to 90 minutes on Day 1 of each 3 week cycle.	Bevacizumab + Capecitabine (1250 mg/m^2)

Measure	Description	Time Frame
Percentage of Participants With Disease Progression or Death	Disease progression was defined according to National Cancer Institute (NCI) guidelines and best clinical practices.	Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death
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.	Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death

Measure	Description	Time Frame
Percentage of Participants Who Died	Overall survival is defined as the time from date of randomization until death from any cause	Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death
Overall Survival

Name	Affiliation	Role
Clinical Trials	Hoffmann-La Roche	Study Chair

ID	Title	Description
FG000	Bevacizumab + Irinotecan + Capecitabine (1000 mg/m^2)	Bevacizumab was administered as a 7.5 milligrams per kilogram (mg/kg) intravenous infusion over 30 to 90 minutes on Day 1 of each 3 week cycle. Irinotecan was administered as a 240 milligrams per meter squared (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 stable disease (SD) were treated with bevacizumab alone until unacceptable toxicity, progressive disease (PD), or participant withdrawal.

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percentage of Participants With Disease Progression or Death

Disease progression was defined according to National Cancer Institute (NCI) guidelines and best clinical practices.

ITT Population;

Posted

Number

percentage of participants

Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death

ID	Title	Description
OG000	Bevacizumab + Irinotecan + Capecitabine (1000 mg/m^2)	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.
OG001	Bevacizumab + Capecitabine (1250 mg/m^2)	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.
OG002	Bevacizumab + Capecitabine (650 mg/m^2)	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 continuous capecitabine treatment. Participants received the same regimen until unacceptable toxicity, PD, or participant withdrawal.

Units	Counts
Participants	OG000101 OG001102 OG002103

Title

Denominators

Categories

Title	Measurements
	OG00086.14 OG00190.20 OG00288.35

Secondary

Percentage of Participants Who Died

Overall survival is defined as the time from date of randomization until death from any cause

ITT Population

Posted

Number

percentage of participants

Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death

ID	Title	Description
OG000	Bevacizumab + Irinotecan + Capecitabine (1000 mg/m^2)	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.
OG001	Bevacizumab + Capecitabine (1250 mg/m^2)	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.

Secondary

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.

ITT Population; Only participants with an event (death) were included in the analysis.

Posted

Median

95% Confidence Interval

months

Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death

ID	Title	Description
OG000	Bevacizumab + Irinotecan + Capecitabine (1000 mg/m^2)	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.
OG001	Bevacizumab + Capecitabine (1250 mg/m^2)	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.

Secondary

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.

ITT Population

Posted

Number

percentage of participants

Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death

ID	Title	Description
OG000	Bevacizumab + Irinotecan + Capecitabine (1000 mg/m^2)	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.
OG001	Bevacizumab + Capecitabine (1250 mg/m^2)	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.

Secondary

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.

ITT Population; only participants with a treatment failure event were included in the analysis.

Posted

Median

95% Confidence Interval

months

Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death

ID	Title	Description
OG000	Bevacizumab + Irinotecan + Capecitabine (1000 mg/m^2)	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.
OG001	Bevacizumab + Capecitabine (1250 mg/m^2)	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.

Secondary

Percentage of Participants With Progression Excluding Deaths

The failure event was defined as tumor progression excluding deaths due to any reason.

ITT Population

Posted

Number

percentage of participants

Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death

ID	Title	Description
OG000	Bevacizumab + Irinotecan + Capecitabine (1000 mg/m^2)	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.
OG001	Bevacizumab + Capecitabine (1250 mg/m^2)	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.

Secondary

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.

ITT Population; Only participants with a time to progression event (excluding deaths) were included in the analysis.

Posted

Median

95% Confidence Interval

months

Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death

ID	Title	Description
OG000	Bevacizumab + Irinotecan + Capecitabine (1000 mg/m^2)	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.
OG001	Bevacizumab + Capecitabine (1250 mg/m^2)	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.

Secondary

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.

ITT Population

Posted

Number

percentage of participants

Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death

ID	Title	Description
OG000	Bevacizumab + Irinotecan + Capecitabine (1000 mg/m^2)	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.
OG001	Bevacizumab + Capecitabine (1250 mg/m^2)	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..

Secondary

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.

ITT Population; only participants with a time to progression event (excluding deaths not related to underlying cancer) were included in the analysis.

Posted

Median

95% Confidence Interval

months

Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death

ID	Title	Description
OG000	Bevacizumab + Irinotecan + Capecitabine (1000 mg/m^2)	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.
OG001	Bevacizumab + Capecitabine (1250 mg/m^2)	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.

Primary

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.

ITT Population; only those participants with an event of disease progression or death were included in the analysis

Posted

Median

95% Confidence Interval

months

Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death

ID	Title	Description
OG000	Bevacizumab + Irinotecan + Capecitabine (1000 mg/m^2)	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.
OG001	Bevacizumab + Capecitabine (1250 mg/m^2)	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.

Secondary

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;

ITT Population; All participants with evaluable data were included in the analysis

Posted

Number

percentage of participants

Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death

ID	Title	Description
OG000	Bevacizumab + Irinotecan + Capecitabine (1000 mg/m^2)	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.

Secondary

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;

ITT Population; All participants with evaluable data were included in the analysis

Posted

Number

95% Confidence Interval

percentage of participants

Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death

ID	Title	Description
OG000	Bevacizumab + Irinotecan + Capecitabine (1000 mg/m^2)	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.
OG001	Bevacizumab + Capecitabine (1250 mg/m^2)	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.

Secondary

Percentage of Participants With Stable Disease

Stable disease rate was the proportion of participants who achieved CR, PR, or SD.

ITT Population; All participants with evaluable data were included in the analysis

Posted

Number

95% Confidence Interval

percentage of participants

Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death

ID	Title	Description
OG000	Bevacizumab + Irinotecan + Capecitabine (1000 mg/m^2)	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.
OG001	Bevacizumab + Capecitabine (1250 mg/m^2)	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.

Secondary

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.

ITT Population; All participants with evaluable data were included in the analysis.

Posted

Number

95% Confidence Interval

percentage of participants

Randomization, Weeks 3, 6 and 9, and 12

ID	Title	Description
OG000	Bevacizumab + Irinotecan + Capecitabine (1000 mg/m^2)	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.
OG001	Bevacizumab + Capecitabine (1250 mg/m^2)	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.

Secondary

Duration of Overall Response

Duration of overall response included participants who achieved a CR or PR.

ITT Population; only participants with a best overall response of CR or PR were included in the analysis.

Posted

Median

95% Confidence Interval

months

Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death

ID	Title	Description
OG000	Bevacizumab + Irinotecan + Capecitabine (1000 mg/m^2)	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.
OG001	Bevacizumab + Capecitabine (1250 mg/m^2)	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.

Secondary

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.

ITT Population; Only participants with a best overall response of CR, PR, or SD were included in the analysis.

Posted

Median

95% Confidence Interval

months

Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death

ID	Title	Description
OG000	Bevacizumab + Irinotecan + Capecitabine (1000 mg/m^2)	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.
OG001	Bevacizumab + Capecitabine (1250 mg/m^2)	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.

Secondary

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.

ITT Population; Only participants with a best overall response were included in the analysis.

Posted

Median

95% Confidence Interval

months

Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years

ID	Title	Description
OG000	Bevacizumab + Irinotecan + Capecitabine (1000 mg/m^2)	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.
OG001	Bevacizumab + Capecitabine (1250 mg/m^2)	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.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA (8.1)	Non-systematic Assessment	EG0003 affected100 at risk EG0010 affected99 at risk EG0020 affected102 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0010 affected99 at risk EG0020 affected102 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA (8.1)	Non-systematic Assessment	EG0007 affected100 at risk EG0011 affected99 at risk EG0021 affected102 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA (8.1)	Non-systematic Assessment	EG0006 affected100 at risk EG0010 affected99 at risk EG0022 affected102 at risk
Vomiting	Gastrointestinal disorders	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0011 affected99 at risk EG0020 affected102 at risk
Disseminated intravascular coagulation	Blood and lymphatic system disorders	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0010 affected99 at risk EG0020 affected102 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA (8.1)	Non-systematic Assessment	EG0002 affected100 at risk EG0010 affected99 at risk EG0020 affected102 at risk
Pancytopenia	Blood and lymphatic system disorders	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0010 affected99 at risk EG0020 affected102 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0011 affected99 at risk EG0020 affected102 at risk
Arrhythmia	Cardiac disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0010 affected99 at risk EG0021 affected102 at risk
Cardiac failure	Cardiac disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0010 affected99 at risk EG0021 affected102 at risk
Myocardial infarction	Cardiac disorders	MedDRA (8.1)	Non-systematic Assessment	EG0002 affected100 at risk EG0010 affected99 at risk EG0020 affected102 at risk
Myocardial ischemia	Cardiac disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0011 affected99 at risk EG0020 affected102 at risk
Supraventricular tachycardia	Cardiac disorders	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0010 affected99 at risk EG0020 affected102 at risk
Abdominal haematoma	Gastrointestinal disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0011 affected99 at risk EG0020 affected102 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0012 affected99 at risk EG0022 affected102 at risk
Gastrointestinal disorder	Gastrointestinal disorders	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0010 affected99 at risk EG0020 affected102 at risk
Intestinal haemorrhage	Gastrointestinal disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0010 affected99 at risk EG0021 affected102 at risk
Intestinal prolapse	Gastrointestinal disorders	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0010 affected99 at risk EG0020 affected102 at risk
Nausea	Gastrointestinal disorders	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0010 affected99 at risk EG0020 affected102 at risk
Pancreatitis	Gastrointestinal disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0010 affected99 at risk EG0021 affected102 at risk
Rectal haemorrhage	Gastrointestinal disorders	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0010 affected99 at risk EG0020 affected102 at risk
Subileus	Gastrointestinal disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0011 affected99 at risk EG0020 affected102 at risk
Swollen tongue	Gastrointestinal disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0011 affected99 at risk EG0020 affected102 at risk
Chest pain	General disorders	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0010 affected99 at risk EG0020 affected102 at risk
Disease progression	General disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0011 affected99 at risk EG0022 affected102 at risk
General physical health deterioration	General disorders	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0011 affected99 at risk EG0020 affected102 at risk
Mucosal inflammation	General disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0011 affected99 at risk EG0020 affected102 at risk
Pyrexia	General disorders	MedDRA (8.1)	Non-systematic Assessment	EG0003 affected100 at risk EG0011 affected99 at risk EG0021 affected102 at risk
Sudden death	General disorders	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0010 affected99 at risk EG0020 affected102 at risk
Jaundice cholestatic	Hepatobiliary disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0010 affected99 at risk EG0021 affected102 at risk
Central line infection	Infections and infestations	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0011 affected99 at risk EG0020 affected102 at risk
Infection	Infections and infestations	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0010 affected99 at risk EG0021 affected102 at risk
Septic shock	Infections and infestations	MedDRA (8.1)	Non-systematic Assessment	EG0002 affected100 at risk EG0010 affected99 at risk EG0020 affected102 at risk
Tuberculosis	Infections and infestations	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0011 affected99 at risk EG0020 affected102 at risk
Device migration	Injury, poisoning and procedural complications	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0010 affected99 at risk EG0020 affected102 at risk
Wound dehiscence	Injury, poisoning and procedural complications	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0010 affected99 at risk EG0020 affected102 at risk
Anorexia	Metabolism and nutrition disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0010 affected99 at risk EG0021 affected102 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0010 affected99 at risk EG0020 affected102 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0010 affected99 at risk EG0020 affected102 at risk
Lung squamous cell carcinoma stage unspecified	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0010 affected99 at risk EG0020 affected102 at risk
Cerebral ischaemia	Nervous system disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0011 affected99 at risk EG0020 affected102 at risk
Dizziness	Nervous system disorders	MedDRA (8.1)	Non-systematic Assessment	EG0002 affected100 at risk EG0010 affected99 at risk EG0020 affected102 at risk
Spinal cord compression	Nervous system disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0011 affected99 at risk EG0020 affected102 at risk
Syncope	Nervous system disorders	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0011 affected99 at risk EG0020 affected102 at risk
Calculus urinary	Renal and urinary disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0011 affected99 at risk EG0020 affected102 at risk
Hydronephrosis	Renal and urinary disorders	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0010 affected99 at risk EG0020 affected102 at risk
Nephrotic syndrome	Renal and urinary disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0010 affected99 at risk EG0021 affected102 at risk
Renal failure	Renal and urinary disorders	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0010 affected99 at risk EG0021 affected102 at risk
Renal vein thrombosis	Renal and urinary disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0010 affected99 at risk EG0021 affected102 at risk
Pharyngeal oedema	Respiratory, thoracic and mediastinal disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0011 affected99 at risk EG0020 affected102 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0011 affected99 at risk EG0020 affected102 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0010 affected99 at risk EG0021 affected102 at risk
Pulmonary artery thrombosis	Respiratory, thoracic and mediastinal disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0011 affected99 at risk EG0020 affected102 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA (8.1)	Non-systematic Assessment	EG0002 affected100 at risk EG0012 affected99 at risk EG0020 affected102 at risk
Pulmonary microemboll	Respiratory, thoracic and mediastinal disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0010 affected99 at risk EG0021 affected102 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0010 affected99 at risk EG0021 affected102 at risk
Toe amputation	Surgical and medical procedures	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0011 affected99 at risk EG0020 affected102 at risk
Deep vein thrombosis	Vascular disorders	MedDRA (8.1)	Non-systematic Assessment	EG0002 affected100 at risk EG0013 affected99 at risk EG0020 affected102 at risk
Embolism	Vascular disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0010 affected99 at risk EG0021 affected102 at risk
Hypertension	Vascular disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0010 affected99 at risk EG0021 affected102 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA (8.1)	Non-systematic Assessment	EG00018 affected100 at risk EG0017 affected99 at risk EG0026 affected102 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA (8.1)	Non-systematic Assessment	EG0007 affected100 at risk EG0012 affected99 at risk EG0022 affected102 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA (8.1)	Non-systematic Assessment	EG00033 affected100 at risk EG0015 affected99 at risk EG0026 affected102 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA (8.1)	Non-systematic Assessment	EG0005 affected100 at risk EG0011 affected99 at risk EG0022 affected102 at risk
Conjunctivitis	Eye disorders	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0016 affected99 at risk EG0022 affected102 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA (8.1)	Non-systematic Assessment	EG00021 affected100 at risk EG00111 affected99 at risk EG00221 affected102 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA (8.1)	Non-systematic Assessment	EG00013 affected100 at risk EG0018 affected99 at risk EG0028 affected102 at risk
Constipation	Gastrointestinal disorders	MedDRA (8.1)	Non-systematic Assessment	EG00012 affected100 at risk EG00110 affected99 at risk EG0028 affected102 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA (8.1)	Non-systematic Assessment	EG00056 affected100 at risk EG00134 affected99 at risk EG00228 affected102 at risk
Nausea	Gastrointestinal disorders	MedDRA (8.1)	Non-systematic Assessment	EG00035 affected100 at risk EG00116 affected99 at risk EG00226 affected102 at risk
Stomatitis	Gastrointestinal disorders	MedDRA (8.1)	Non-systematic Assessment	EG0006 affected100 at risk EG00110 affected99 at risk EG0022 affected102 at risk
Vomiting	Gastrointestinal disorders	MedDRA (8.1)	Non-systematic Assessment	EG00023 affected100 at risk EG00113 affected99 at risk EG0026 affected102 at risk
Asthenia	General disorders	MedDRA (8.1)	Non-systematic Assessment	EG00016 affected100 at risk EG00117 affected99 at risk EG00220 affected102 at risk
Fatigue	General disorders	MedDRA (8.1)	Non-systematic Assessment	EG00014 affected100 at risk EG00112 affected99 at risk EG00216 affected102 at risk
Mucosal inflammation	General disorders	MedDRA (8.1)	Non-systematic Assessment	EG00013 affected100 at risk EG0019 affected99 at risk EG0027 affected102 at risk
Pyrexia	General disorders	MedDRA (8.1)	Non-systematic Assessment	EG00030 affected100 at risk EG00117 affected99 at risk EG00215 affected102 at risk
Hyperbilirubinaemia	Hepatobiliary disorders	MedDRA (8.1)	Non-systematic Assessment	EG00010 affected100 at risk EG00122 affected99 at risk EG00226 affected102 at risk
Alanine aminotransferase increased	Investigations	MedDRA (8.1)	Non-systematic Assessment	EG0007 affected100 at risk EG0019 affected99 at risk EG00212 affected102 at risk
Aspartate aminotransferase increased	Investigations	MedDRA (8.1)	Non-systematic Assessment	EG0006 affected100 at risk EG0018 affected99 at risk EG00211 affected102 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA (8.1)	Non-systematic Assessment	EG0006 affected100 at risk EG0014 affected99 at risk EG0024 affected102 at risk
Anorexia	Metabolism and nutrition disorders	MedDRA (8.1)	Non-systematic Assessment	EG0009 affected100 at risk EG0015 affected99 at risk EG0025 affected102 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (8.1)	Non-systematic Assessment	EG0005 affected100 at risk EG0014 affected99 at risk EG0024 affected102 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (8.1)	Non-systematic Assessment	EG0005 affected100 at risk EG0012 affected99 at risk EG0024 affected102 at risk
Headache	Nervous system disorders	MedDRA (8.1)	Non-systematic Assessment	EG0004 affected100 at risk EG0017 affected99 at risk EG0025 affected102 at risk
Cholinergic syndrome	Nervous system disorders	MedDRA (8.1)	Non-systematic Assessment	EG0005 affected100 at risk EG0010 affected99 at risk EG0020 affected102 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (8.1)	Non-systematic Assessment	EG0005 affected100 at risk EG0013 affected99 at risk EG0026 affected102 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (8.1)	Non-systematic Assessment	EG0004 affected100 at risk EG0015 affected99 at risk EG0026 affected102 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA (8.1)	Non-systematic Assessment	EG00014 affected100 at risk EG0016 affected99 at risk EG0027 affected102 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA (8.1)	Non-systematic Assessment	EG00022 affected100 at risk EG0012 affected99 at risk EG0023 affected102 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA (8.1)	Non-systematic Assessment	EG0005 affected100 at risk EG0010 affected99 at risk EG0021 affected102 at risk
Palmar-plantar erythrodysaesthesia syndrome	Skin and subcutaneous tissue disorders	MedDRA (8.1)	Non-systematic Assessment	EG00016 affected100 at risk EG00140 affected99 at risk EG00239 affected102 at risk
Hypertension	Vascular disorders	MedDRA (8.1)	Non-systematic Assessment	EG00028 affected100 at risk EG00129 affected99 at risk EG00219 affected102 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA (8.1)	Non-systematic Assessment	EG0003 affected100 at risk EG0011 affected99 at risk EG0020 affected102 at risk
Granulocytopenia	Blood and lymphatic system disorders	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0010 affected99 at risk EG0020 affected102 at risk
Leukocytosis	Blood and lymphatic system disorders	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0011 affected99 at risk EG0021 affected102 at risk
Pancytopenia	Blood and lymphatic system disorders	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0010 affected99 at risk EG0020 affected102 at risk
Arrhythmia	Cardiac disorders	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0010 affected99 at risk EG0020 affected102 at risk
Atrial tachycardia	Cardiac disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0010 affected99 at risk EG0021 affected102 at risk
Bradycardia	Cardiac disorders	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0010 affected99 at risk EG0020 affected102 at risk
Cyanosis	Cardiac disorders	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0010 affected99 at risk EG0020 affected102 at risk
Extrasystoles	Cardiac disorders	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0010 affected99 at risk EG0020 affected102 at risk
Palpitations	Cardiac disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0012 affected99 at risk EG0021 affected102 at risk
Sinus tachycardia	Cardiac disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0011 affected99 at risk EG0020 affected102 at risk
Tachycardia	Cardiac disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0012 affected99 at risk EG0021 affected102 at risk
Ventricular extrasystoles	Cardiac disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0011 affected99 at risk EG0020 affected102 at risk
Ear pain	Ear and labyrinth disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0011 affected99 at risk EG0021 affected102 at risk
Vertigo	Ear and labyrinth disorders	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0012 affected99 at risk EG0023 affected102 at risk
Hypothyroidism	Endocrine disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0011 affected99 at risk EG0020 affected102 at risk
Conjunctival haemorrhage	Eye disorders	MedDRA (8.1)	Non-systematic Assessment	EG0002 affected100 at risk EG0010 affected99 at risk EG0020 affected102 at risk
Diplopia	Eye disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0011 affected99 at risk EG0020 affected102 at risk
Eye inflammation	Eye disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0010 affected99 at risk EG0021 affected102 at risk
Glaucoma	Eye disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0010 affected99 at risk EG0021 affected102 at risk
Ocular discomfort	Eye disorders	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0010 affected99 at risk EG0020 affected102 at risk
Ocular icterus	Eye disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0011 affected99 at risk EG0020 affected102 at risk
Vision blurred	Eye disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0011 affected99 at risk EG0020 affected102 at risk
Abdominal discomfort	Gastrointestinal disorders	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0010 affected99 at risk EG0021 affected102 at risk
Anal discomfort	Gastrointestinal disorders	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0010 affected99 at risk EG0021 affected102 at risk
Ano-rectal ulcer	Gastrointestinal disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0011 affected99 at risk EG0020 affected102 at risk
Ascites	Gastrointestinal disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0011 affected99 at risk EG0021 affected102 at risk
Cheilitis	Gastrointestinal disorders	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0010 affected99 at risk EG0020 affected102 at risk
Dry mouth	Gastrointestinal disorders	MedDRA (8.1)	Non-systematic Assessment	EG0002 affected100 at risk EG0010 affected99 at risk EG0020 affected102 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA (8.1)	Non-systematic Assessment	EG0004 affected100 at risk EG0013 affected99 at risk EG0024 affected102 at risk
Enteritis	Gastrointestinal disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0010 affected99 at risk EG0021 affected102 at risk
Flatulence	Gastrointestinal disorders	MedDRA (8.1)	Non-systematic Assessment	EG0002 affected100 at risk EG0010 affected99 at risk EG0020 affected102 at risk
Gastritis	Gastrointestinal disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0011 affected99 at risk EG0020 affected102 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0011 affected99 at risk EG0020 affected102 at risk
Gingival bleeding	Gastrointestinal disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0012 affected99 at risk EG0020 affected102 at risk
Gingivitis	Gastrointestinal disorders	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0010 affected99 at risk EG0021 affected102 at risk
Haematochezia	Gastrointestinal disorders	MedDRA (8.1)	Non-systematic Assessment	EG0003 affected100 at risk EG0011 affected99 at risk EG0021 affected102 at risk
Haemorrhoids	Gastrointestinal disorders	MedDRA (8.1)	Non-systematic Assessment	EG0003 affected100 at risk EG0012 affected99 at risk EG0022 affected102 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0010 affected99 at risk EG0020 affected102 at risk
Mesenteric vein thrombosis	Gastrointestinal disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0010 affected99 at risk EG0021 affected102 at risk
Mouth haemorrhage	Gastrointestinal disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0010 affected99 at risk EG0021 affected102 at risk
Mouth ulceration	Gastrointestinal disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0013 affected99 at risk EG0020 affected102 at risk
Oral discomfort	Gastrointestinal disorders	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0010 affected99 at risk EG0020 affected102 at risk
Oedema peripheral	Gastrointestinal disorders	MedDRA (8.1)	Non-systematic Assessment	EG0002 affected100 at risk EG0011 affected99 at risk EG0021 affected102 at risk
Periodontitis	Gastrointestinal disorders	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0010 affected99 at risk EG0020 affected102 at risk
Polyp colorectal	Gastrointestinal disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0011 affected99 at risk EG0020 affected102 at risk
Proctalgia	Gastrointestinal disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0011 affected99 at risk EG0022 affected102 at risk
Proctitis	Gastrointestinal disorders	MedDRA (8.1)	Non-systematic Assessment	EG0002 affected100 at risk EG0011 affected99 at risk EG0021 affected102 at risk
Rectal haemorrhage	Gastrointestinal disorders	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0012 affected99 at risk EG0022 affected102 at risk
Toothache	Gastrointestinal disorders	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0010 affected99 at risk EG0022 affected102 at risk
Catheter site related reaction	General disorders	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0010 affected99 at risk EG0020 affected102 at risk
Chest discomfort	General disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0011 affected99 at risk EG0021 affected102 at risk
Chest pain	General disorders	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0013 affected99 at risk EG0024 affected102 at risk
Facial pain	General disorders	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0010 affected99 at risk EG0020 affected102 at risk
General physical health deterioration	General disorders	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0011 affected99 at risk EG0022 affected102 at risk
Influenza-like illness	General disorders	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0013 affected99 at risk EG0021 affected102 at risk
Local swelling	General disorders	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0010 affected99 at risk EG0020 affected102 at risk
Malaise	General disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0011 affected99 at risk EG0021 affected102 at risk
Oedema peripheral	General disorders	MedDRA (8.1)	Non-systematic Assessment	EG0002 affected100 at risk EG0011 affected99 at risk EG0021 affected102 at risk
Pain	General disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0012 affected99 at risk EG0021 affected102 at risk
Hepatic failure	Hepatobiliary disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0010 affected99 at risk EG0021 affected102 at risk
Hepatic pain	Hepatobiliary disorders	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0010 affected99 at risk EG0020 affected102 at risk
Hepatotoxicity	Hepatobiliary disorders	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0010 affected99 at risk EG0021 affected102 at risk
Jaundice	Hepatobiliary disorders	MedDRA (8.1)	Non-systematic Assessment	EG0003 affected100 at risk EG0010 affected99 at risk EG0022 affected102 at risk
Abdominal wall infection	Infections and infestations	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0011 affected99 at risk EG0020 affected102 at risk
Bacteriuria	Infections and infestations	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0011 affected99 at risk EG0020 affected102 at risk
Bronchitis	Infections and infestations	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0012 affected99 at risk EG0022 affected102 at risk
Cellulitis	Infections and infestations	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0011 affected99 at risk EG0020 affected102 at risk
Cystitis	Infections and infestations	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0014 affected99 at risk EG0021 affected102 at risk
Dental caries	Infections and infestations	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0010 affected99 at risk EG0021 affected102 at risk
Ear infection	Infections and infestations	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0010 affected99 at risk EG0021 affected102 at risk
Erysipelas	Infections and infestations	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0010 affected99 at risk EG0021 affected102 at risk
Folliculitis	Infections and infestations	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0010 affected99 at risk EG0020 affected102 at risk
Gastroenteritis viral	Infections and infestations	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0011 affected99 at risk EG0020 affected102 at risk
Herpes zoster	Infections and infestations	MedDRA (8.1)	Non-systematic Assessment	EG0002 affected100 at risk EG0010 affected99 at risk EG0021 affected102 at risk
Influenza	Infections and infestations	MedDRA (8.1)	Non-systematic Assessment	EG0003 affected100 at risk EG0014 affected99 at risk EG0025 affected102 at risk
Nail infection	Infections and infestations	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0011 affected99 at risk EG0020 affected102 at risk
Paronychia	Infections and infestations	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0010 affected99 at risk EG0021 affected102 at risk
Perianal abscess	Infections and infestations	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0011 affected99 at risk EG0020 affected102 at risk
Pharyngitis	Infections and infestations	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0010 affected99 at risk EG0021 affected102 at risk
Relapsing fever	Infections and infestations	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0010 affected99 at risk EG0021 affected102 at risk
Rhinitis	Infections and infestations	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0011 affected99 at risk EG0020 affected102 at risk
Subcutaneous abscess	Infections and infestations	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0011 affected99 at risk EG0020 affected102 at risk
Tooth abscess	Infections and infestations	MedDRA (8.1)	Non-systematic Assessment	EG0003 affected100 at risk EG0011 affected99 at risk EG0022 affected102 at risk
Urinary tract infection	Infections and infestations	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0010 affected99 at risk EG0023 affected102 at risk
Vaginal infection	Infections and infestations	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0010 affected99 at risk EG0020 affected102 at risk
Intestinal stoma complication	Injury, poisoning and procedural complications	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0011 affected99 at risk EG0021 affected102 at risk
Radius fracture	Injury, poisoning and procedural complications	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0011 affected99 at risk EG0020 affected102 at risk
Wound	Injury, poisoning and procedural complications	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0010 affected99 at risk EG0020 affected102 at risk
Wound dehiscence	Injury, poisoning and procedural complications	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0011 affected99 at risk EG0020 affected102 at risk
Blood alkaline phosphatase	Investigations	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0010 affected99 at risk EG0020 affected102 at risk
Blood bilirubin	Investigations	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0010 affected99 at risk EG0021 affected102 at risk
Blood calcium decreased	Investigations	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0010 affected99 at risk EG0020 affected102 at risk
Blood calcium increased	Investigations	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0010 affected99 at risk EG0020 affected102 at risk
Blood creatine increased	Investigations	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0011 affected99 at risk EG0020 affected102 at risk
Blood creatinine increased	Investigations	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0014 affected99 at risk EG0022 affected102 at risk
Blood glucose increased	Investigations	MedDRA (8.1)	Non-systematic Assessment	EG0002 affected100 at risk EG0011 affected99 at risk EG0021 affected102 at risk
Blood lactate dehydrogenase increased	Investigations	MedDRA (8.1)	Non-systematic Assessment	EG0002 affected100 at risk EG0012 affected99 at risk EG0021 affected102 at risk
Blood sodium increased	Investigations	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0010 affected99 at risk EG0020 affected102 at risk
Coagulation test abnormal	Investigations	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0010 affected99 at risk EG0020 affected102 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0011 affected99 at risk EG0021 affected102 at risk
Haematocrit decreased	Investigations	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0010 affected99 at risk EG0020 affected102 at risk
Hepatic enzyme increased	Investigations	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0010 affected99 at risk EG0021 affected102 at risk
Platelet count increased	Investigations	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0010 affected99 at risk EG0021 affected102 at risk
Prothrombin time shortened	Investigations	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0010 affected99 at risk EG0020 affected102 at risk
Transaminases increased	Investigations	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0013 affected99 at risk EG0020 affected102 at risk
Weight decreased	Investigations	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0010 affected99 at risk EG0022 affected102 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0010 affected99 at risk EG0020 affected102 at risk
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0011 affected99 at risk EG0021 affected102 at risk
Gout	Metabolism and nutrition disorders	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0010 affected99 at risk EG0020 affected102 at risk
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0011 affected99 at risk EG0021 affected102 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA (8.1)	Non-systematic Assessment	EG0002 affected100 at risk EG0011 affected99 at risk EG0020 affected102 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA (8.1)	Non-systematic Assessment	EG0002 affected100 at risk EG0010 affected99 at risk EG0021 affected102 at risk
Hypertriglyceridaemia	Metabolism and nutrition disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0011 affected99 at risk EG0021 affected102 at risk
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA (8.1)	Non-systematic Assessment	EG0002 affected100 at risk EG0011 affected99 at risk EG0023 affected102 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0010 affected99 at risk EG0022 affected102 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0010 affected99 at risk EG0021 affected102 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (8.1)	Non-systematic Assessment	EG0003 affected100 at risk EG0011 affected99 at risk EG0022 affected102 at risk
Arthritis	Musculoskeletal and connective tissue disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0010 affected99 at risk EG0021 affected102 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA (8.1)	Non-systematic Assessment	EG0003 affected100 at risk EG0010 affected99 at risk EG0021 affected102 at risk
Buttock pain	Musculoskeletal and connective tissue disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0010 affected99 at risk EG0021 affected102 at risk
Chest wall pain	Musculoskeletal and connective tissue disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0012 affected99 at risk EG0021 affected102 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0010 affected99 at risk EG0022 affected102 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0011 affected99 at risk EG0020 affected102 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0012 affected99 at risk EG0021 affected102 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0012 affected99 at risk EG0023 affected102 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (8.1)	Non-systematic Assessment	EG0002 affected100 at risk EG0012 affected99 at risk EG0025 affected102 at risk
Periarthritis	Musculoskeletal and connective tissue disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0011 affected99 at risk EG0020 affected102 at risk
Sacral pain	Musculoskeletal and connective tissue disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0011 affected99 at risk EG0020 affected102 at risk
Shoulder pain	Musculoskeletal and connective tissue disorders	MedDRA (8.1)	Non-systematic Assessment	EG0003 affected100 at risk EG0012 affected99 at risk EG0022 affected102 at risk
Tendonitis	Musculoskeletal and connective tissue disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0011 affected99 at risk EG0020 affected102 at risk
Carpal tunnel syndrome	Nervous system disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0011 affected99 at risk EG0020 affected102 at risk
Coordination abnormal	Nervous system disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0011 affected99 at risk EG0020 affected102 at risk
Dizziness	Nervous system disorders	MedDRA (8.1)	Non-systematic Assessment	EG0003 affected100 at risk EG0010 affected99 at risk EG0021 affected102 at risk
Dysaesthesia	Nervous system disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0011 affected99 at risk EG0020 affected102 at risk
Dysguesia	Nervous system disorders	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0010 affected99 at risk EG0021 affected102 at risk
Migraine without aura	Nervous system disorders	MedDRA (8.1)	Non-systematic Assessment	EG0002 affected100 at risk EG0010 affected99 at risk EG0020 affected102 at risk
Neuropathy	Nervous system disorders	MedDRA (8.1)	Non-systematic Assessment	EG0003 affected100 at risk EG0010 affected99 at risk EG0021 affected102 at risk
Paraesthesia	Nervous system disorders	MedDRA (8.1)	Non-systematic Assessment	EG0004 affected100 at risk EG0013 affected99 at risk EG0025 affected102 at risk
Sciatica	Nervous system disorders	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0013 affected99 at risk EG0022 affected102 at risk
Somnolence	Nervous system disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0011 affected99 at risk EG0020 affected102 at risk
Syncope	Nervous system disorders	MedDRA (8.1)	Non-systematic Assessment	EG0002 affected100 at risk EG0010 affected99 at risk EG0020 affected102 at risk
Anxiety	Psychiatric disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0013 affected99 at risk EG0021 affected102 at risk
Confusional state	Psychiatric disorders	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0010 affected99 at risk EG0021 affected102 at risk
Depression	Psychiatric disorders	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0011 affected99 at risk EG0023 affected102 at risk
Insomnia	Psychiatric disorders	MedDRA (8.1)	Non-systematic Assessment	EG0002 affected100 at risk EG0012 affected99 at risk EG0021 affected102 at risk
Mood altered	Psychiatric disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0011 affected99 at risk EG0021 affected102 at risk
Panic attack	Psychiatric disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0010 affected99 at risk EG0021 affected102 at risk
Restlessness	Psychiatric disorders	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0010 affected99 at risk EG0020 affected102 at risk
Bladder spasm	Renal and urinary disorders	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0010 affected99 at risk EG0020 affected102 at risk
Dysuria	Renal and urinary disorders	MedDRA (8.1)	Non-systematic Assessment	EG0002 affected100 at risk EG0010 affected99 at risk EG0020 affected102 at risk
Nocturia	Renal and urinary disorders	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0010 affected99 at risk EG0021 affected102 at risk
Pollakiuria	Renal and urinary disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0010 affected99 at risk EG0021 affected102 at risk
Proteinuria	Renal and urinary disorders	MedDRA (8.1)	Non-systematic Assessment	EG0004 affected100 at risk EG0014 affected99 at risk EG0024 affected102 at risk
Renal colic	Renal and urinary disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0010 affected99 at risk EG0021 affected102 at risk
Renal failure acute	Renal and urinary disorders	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0010 affected99 at risk EG0020 affected102 at risk
Ureteric obstruction	Renal and urinary disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0011 affected99 at risk EG0020 affected102 at risk
Ureteric stenosis	Renal and urinary disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0011 affected99 at risk EG0020 affected102 at risk
Female genital-digestive tract fistula	Reproductive system and breast disorders	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0010 affected99 at risk EG0020 affected102 at risk
Pelvic pain	Reproductive system and breast disorders	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0010 affected99 at risk EG0020 affected102 at risk
Penis disorder	Reproductive system and breast disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0013 affected99 at risk EG0021 affected102 at risk
Vaginal haemorrhage	Reproductive system and breast disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0010 affected99 at risk EG0022 affected102 at risk
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0010 affected99 at risk EG0022 affected102 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0011 affected99 at risk EG0020 affected102 at risk
Pharyngolaryngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA (8.1)	Non-systematic Assessment	EG0004 affected100 at risk EG0013 affected99 at risk EG0021 affected102 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0011 affected99 at risk EG0020 affected102 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0011 affected99 at risk EG0020 affected102 at risk
Rhinorrhoea	Reproductive system and breast disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0011 affected99 at risk EG0020 affected102 at risk
Sleep apnoea syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0011 affected99 at risk EG0020 affected102 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0012 affected99 at risk EG0020 affected102 at risk
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0010 affected99 at risk EG0021 affected102 at risk
Nail disorder	Skin and subcutaneous tissue disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0010 affected99 at risk EG0021 affected102 at risk
Nail dystrophy	Skin and subcutaneous tissue disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0010 affected99 at risk EG0021 affected102 at risk
Onycholysis	Skin and subcutaneous tissue disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0012 affected99 at risk EG0020 affected102 at risk
Photosensitivity reaction	Skin and subcutaneous tissue disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0010 affected99 at risk EG0021 affected102 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0011 affected99 at risk EG0022 affected102 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA (8.1)	Non-systematic Assessment	EG0003 affected100 at risk EG0011 affected99 at risk EG0023 affected102 at risk
Rash papular	Skin and subcutaneous tissue disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0010 affected99 at risk EG0021 affected102 at risk
Skin exfoliation	Skin and subcutaneous tissue disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0010 affected99 at risk EG0021 affected102 at risk
Skin fissures	Skin and subcutaneous tissue disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0012 affected99 at risk EG0020 affected102 at risk
Urticaria	Skin and subcutaneous tissue disorders	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0011 affected99 at risk EG0020 affected102 at risk
Cataract operation	Surgical and medical procedures	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0011 affected99 at risk EG0020 affected102 at risk
Inguinal hernia repair	Surgical and medical procedures	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0010 affected99 at risk EG0021 affected102 at risk
Stent placement	Surgical and medical procedures	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0010 affected99 at risk EG0020 affected102 at risk
Tooth extraction	Surgical and medical procedures	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0011 affected99 at risk EG0020 affected102 at risk
Axillary vein thrombosis	Vascular disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0010 affected99 at risk EG0021 affected102 at risk
Deep vein thrombosis	Vascular disorders	MedDRA (8.1)	Non-systematic Assessment	EG0003 affected100 at risk EG0011 affected99 at risk EG0021 affected102 at risk
Haemorrhage	Vascular disorders	MedDRA (8.1)	Non-systematic Assessment	EG0000 affected100 at risk EG0010 affected99 at risk EG0021 affected102 at risk
Hypotension	Vascular disorders	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0011 affected99 at risk EG0020 affected102 at risk
Phlebitis	Vascular disorders	MedDRA (8.1)	Non-systematic Assessment	EG0001 affected100 at risk EG0010 affected99 at risk EG0020 affected102 at risk
Thrombosis	Vascular disorders	MedDRA (8.1)	Non-systematic Assessment	EG0002 affected100 at risk EG0010 affected99 at risk EG0021 affected102 at risk

Facility	Status	City	State	ZIP	Country	Contacts
		Paola	Calabria	87027	Italy

ID	Term
D007414	Intestinal Neoplasms
D005770	Gastrointestinal Neoplasms
D004067	Digestive System Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D004066	Digestive System Diseases
D005767	Gastrointestinal Diseases
D003108	Colonic Diseases
D007410	Intestinal Diseases
D012002	Rectal Diseases

ID	Term
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins
D003841	Deoxycytidine
D003562	Cytidine
D011741	Pyrimidine Nucleosides
D011743	Pyrimidines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D005472	Fluorouracil
D014498	Uracil
D011744	Pyrimidinones
D003853	Deoxyribonucleosides
D009705	Nucleosides
D009706	Nucleic Acids, Nucleotides, and Nucleosides
D002166	Camptothecin
D000470	Alkaloids

ID	Title	Description
BG000	Bevacizumab + Irinotecan + Capecitabine (1000 mg/m^2)	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.
BG001	Bevacizumab + Capecitabine (1250 mg/m^2)	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.
BG002	Bevacizumab + Capecitabine (650 mg/m^2)	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.
BG003	Total	Total of all reporting groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Bevacizumab + Irinotecan + Capecitabine (1000 mg/m^2)	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.	38	100	95	100
EG001	Bevacizumab + Capecitabine (1250 mg/m^2)	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.	21	99	88	99
EG002	Bevacizumab + Capecitabine (650 mg/m^2)	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.	20	102	85	102

ID	Term
D000068258	Bevacizumab
D000069287	Capecitabine
D000077146	Irinotecan