A Study of Avastin (Bevacizumab) Added to Interferon Alfa... | NCT00738530

NCT00738530

ID	Type	Description	Link
2004-000282-35	EudraCT Number

Status Module

Description Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Bevacizumab + IFN-Alfa-2A	Experimental	Bevacizumab infusions will be administered every 2 weeks at a dose of 10 milligram per kilogram (mg/kg) for 52 weeks or until disease progression or unacceptable toxicity. Interferon alfa-2a (IFN-Alfa-2A) will be administered 3 times per week as a subcutaneous injection at a dose of 9 million international units (MIU) for 52 weeks or until disease progression or major toxicity.	Drug: Bevacizumab [Avastin] Drug: Interferon alfa 2a [Roferon]
Placebo + IFN-Alfa-2A	Placebo Comparator	Placebo matched with Bevacizumab infusions will be administered every 2 weeks for 52 weeks or until disease progression or unacceptable toxicity. IFN-Alfa-2A will be administered 3 times per week as a subcutaneous injection at a dose of 9 MIU for 52 weeks or until disease progression or major toxicity.	Drug: Interferon alfa 2a [Roferon] Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Bevacizumab [Avastin]	Drug	10 mg/kg IV every 2 weeks	Bevacizumab + IFN-Alfa-2A

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percentage of Participants Who Died		Baseline up to 4.25 years
Overall Survival (OS) Duration	Duration of survival was defined as the time between the date of randomization and date of death due to any cause. Participants still alive at the time of analysis were censored at the date they were last known to be alive. Kaplan-Meier estimates were used for analysis.	Baseline until death (up to 4.25 years)

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Participants With Disease Progression or Death	Progressive disease was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of one or more new lesions and/or the unequivocal progression of existing non-target lesions.	Baseline until disease progression or death, whichever occurred first (assessed at baseline, Weeks 8, 16, 24, 32, 44, 56, 68 thereafter every 12 weeks up to week 104 and then every 6 months up to 4.25 years)

Eligibility Module

Contacts/Locations Module

Name	Affiliation	Role
Clinical Trials	Hoffmann-La Roche	Study Director

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
37146227	Derived	Aldin A, Besiroglu B, Adams A, Monsef I, Piechotta V, Tomlinson E, Hornbach C, Dressen N, Goldkuhle M, Maisch P, Dahm P, Heidenreich A, Skoetz N. First-line therapy for adults with advanced renal cell carcinoma: a systematic review and network meta-analysis. Cochrane Database Syst Rev. 2023 May 4;5(5):CD013798. doi: 10.1002/14651858.CD013798.pub2.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Bevacizumab + IFN-Alfa-2A	Bevacizumab infusions were administered every 2 weeks at a dose of 10 milligram per kilogram (mg/kg) for 52 weeks or until disease progression or unacceptable toxicity. Interferon alfa-2a (IFN-Alfa-2A) was administered 3 times per week as a subcutaneous injection at a dose of 9 million international units (MIU) for 52 weeks or until disease progression or major toxicity.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Arm/Group Information

ID	Title	Description
BG000	Bevacizumab + IFN-Alfa-2A	Bevacizumab infusions were administered every two weeks at a dose of 10 mg/kg for 52 weeks or until disease progression or unacceptable toxicity. IFN-Alfa-2A was administered 3 times per week as a subcutaneous injection at a dose of 9 MIU for 52 weeks or until disease progression or major toxicity.
BG001	Placebo + IFN-Alfa-2A	Placebo matched with Bevacizumab infusions were administered every two weeks for 52 weeks or until disease progression or unacceptable toxicity. IFN-Alfa-2A was administered 3 times per week as a subcutaneous injection at a dose of 9 MIU for 52 weeks or until disease progression or major toxicity.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	OG00067.3 OG00169.6

Primary

Overall Survival (OS) Duration

Duration of survival was defined as the time between the date of randomization and date of death due to any cause. Participants still alive at the time of analysis were censored at the date they were last known to be alive. Kaplan-Meier estimates were used for analysis.

ITT population included all participants randomized into the study.

Posted

Median

95% Confidence Interval

months

Baseline until death (up to 4.25 years)

ID	Title	Description
OG000	Bevacizumab + IFN-Alfa-2A	Bevacizumab infusions were administered every two weeks at a dose of 10 mg/kg for 52 weeks or until disease progression or unacceptable toxicity. IFN-Alfa-2A was administered 3 times per week as a subcutaneous injection at a dose of 9 MIU for 52 weeks or until disease progression or major toxicity.
OG001	Placebo + IFN-Alfa-2A	Placebo matched with Bevacizumab infusions were administered every two weeks for 52 weeks or until disease progression or unacceptable toxicity. IFN-Alfa-2A was administered 3 times per week as a subcutaneous injection at a dose of 9 MIU for 52 weeks or until disease progression or major toxicity.

Units	Counts

Secondary

Percentage of Participants With Disease Progression or Death

Progressive disease was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of one or more new lesions and/or the unequivocal progression of existing non-target lesions.

ITT population included all participants randomized into the study.

Posted

Number

percentage of participants

Baseline until disease progression or death, whichever occurred first (assessed at baseline, Weeks 8, 16, 24, 32, 44, 56, 68 thereafter every 12 weeks up to week 104 and then every 6 months up to 4.25 years)

ID	Title	Description
OG000	Bevacizumab + IFN-Alfa-2A	Bevacizumab infusions were administered every two weeks at a dose of 10 mg/kg for 52 weeks or until disease progression or unacceptable toxicity. IFN-Alfa-2A was administered 3 times per week as a subcutaneous injection at a dose of 9 MIU for 52 weeks or until disease progression or major toxicity.
OG001	Placebo + IFN-Alfa-2A	Placebo matched with Bevacizumab infusions were administered every two weeks for 52 weeks or until disease progression or unacceptable toxicity. IFN-Alfa-2A was administered 3 times per week as a subcutaneous injection at a dose of 9 MIU for 52 weeks or until disease progression or major toxicity.

Secondary

Progression Free Survival (PFS) According to Modified Response Evaluation Criteria in Solid Tumors (mRECIST)

Progression-free survival was defined as the time between the date of randomization and the first date of documented progression or date of death due to any cause, whichever occurred first. Tumor assessment was performed using modified RECIST. Progressive disease was defined as at least a 20 percentage(%) increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of one or more new lesions and/or the unequivocal progression of existing non-target lesions. Participants without an event were censored at the date of last follow-up for progression or date of last available tumor measurement if no follow-up assessment for progression was performed. Participants who were randomized but not exposed to study drug and had no further follow-up were censored on the day of randomization.

ITT population included all participants randomized into the study.

Posted

Median

95% Confidence Interval

months

ID	Title	Description
OG000	Bevacizumab + IFN-Alfa-2A	Bevacizumab infusions were administered every two weeks at a dose of 10 mg/kg for 52 weeks or until disease progression or unacceptable toxicity. IFN-Alfa-2A was administered 3 times per week as a subcutaneous injection at a dose of 9 MIU for 52 weeks or until disease progression or major toxicity.

Secondary

Time to Progression (TTP) According to Modified Response Evaluation Criteria in Solid Tumors (mRECIST)

Time to progression was defined as the time between date of randomization and date of documented progression. Tumor assessment was performed using mRECIST. Progressive disease was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of one or more new lesions and/or the unequivocal progression of existing non-target lesions. Participants without an event (including participants who died before progressive disease) were censored at the date of last follow-up for progression or date of last available tumor measurement if no follow-up assessment for progression was performed. Participants who were randomized but not exposed to study drug and had no further follow-up were censored on the day of randomization.

ITT population included all participants randomized into the study.

Posted

Median

95% Confidence Interval

months

ID	Title	Description
OG000	Bevacizumab + IFN-Alfa-2A	Bevacizumab infusions were administered every two weeks at a dose of 10 mg/kg for 52 weeks or until disease progression or unacceptable toxicity. IFN-Alfa-2A was administered 3 times per week as a subcutaneous injection at a dose of 9 MIU for 52 weeks or until disease progression or major toxicity.

Secondary

Percentage of Participants With Treatment Failure

Treatment failure is defined as insufficient therapeutic response (including disease progression), death, withdrawal of treatment due to adverse events or laboratory abnormality, or withdrawal of informed consent. Tumor assessment was performed using mRECIST. Progressive disease was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of one or more new lesions and/or the unequivocal progression of existing non-target lesions.

ITT population included all participants randomized into the study.

Posted

Number

percentage of participants

ID	Title	Description
OG000	Bevacizumab + IFN-Alfa-2A	Bevacizumab infusions were administered every two weeks at a dose of 10 mg/kg for 52 weeks or until disease progression or unacceptable toxicity. IFN-Alfa-2A was administered 3 times per week as a subcutaneous injection at a dose of 9 MIU for 52 weeks or until disease progression or major toxicity.
OG001	Placebo + IFN-Alfa-2A	Placebo matched with Bevacizumab infusions were administered every two weeks for 52 weeks or until disease progression or unacceptable toxicity. IFN-Alfa-2A was administered 3 times per week as a subcutaneous injection at a dose of 9 MIU for 52 weeks or until disease progression or major toxicity.

Secondary

Time to Treatment Failure (TTF) According to Modified Response Evaluation Criteria in Solid Tumors (mRECIST)

Time to treatment failure was defined as the time between the date of randomization and the date of insufficient therapeutic response (including disease progression), death, withdrawal of treatment due to adverse events or laboratory abnormality, or withdrawal of informed consent. Tumor assessment was performed using mRECIST. Progressive disease was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of one or more new lesions and/or the unequivocal progression of existing non-target lesions. Participants without an event were censored at the date of last tumor assessment or last treatment administration, whichever occurred last. Participants who were randomized but not exposed to study drug and had no further follow-up were censored on the day of randomization.

ITT population included all participants randomized into the study.

Posted

Median

95% Confidence Interval

months

ID	Title	Description
OG000	Bevacizumab + IFN-Alfa-2A	Bevacizumab infusions were administered every two weeks at a dose of 10 mg/kg for 52 weeks or until disease progression or unacceptable toxicity. IFN-Alfa-2A was administered 3 times per week as a subcutaneous injection at a dose of 9 MIU for 52 weeks or until disease progression or major toxicity.

Secondary

Percentage of Participants With Objective Response According to mRECIST

Objective response referred to participants with complete response (CR) or partial response (PR). CR: disappearance of all target lesions, non-target lesions, and normalization of tumor marker level. PR: greater than or equal to (>=) 30% decrease in sum of the longest diameter (LD) of all target lesions taking as reference the screening sum LD. To be assigned a status of PR or CR, changes in tumor measurements had to be confirmed by repeat assessments that should have been performed no less than 4 weeks after the criteria for response were first met. Longer intervals as determined by the study protocol were also appropriate.

ITT population included all participants randomized into the study. Number of participants analyzed (N) = participants with measurable disease at baseline.

Posted

Number

percentage of participants

ID	Title	Description
OG000	Bevacizumab + IFN-Alfa-2A	Bevacizumab infusions were administered every two weeks at a dose of 10 mg/kg for 52 weeks or until disease progression or unacceptable toxicity. IFN-Alfa-2A was administered 3 times per week as a subcutaneous injection at a dose of 9 MIU for 52 weeks or until disease progression or major toxicity.
OG001	Placebo + IFN-Alfa-2A

Secondary

Percentage of Participants With Best Overall Response According to Modified Response Evaluation Criteria in Solid Tumors (mRECIST)

Best response recorded from the start of treatment until disease progression. Based on assessment of CR, PR, stable disease (SD), or progressive disease (PD), according to mRECIST. CR: disappearance of all target lesions, non-target lesions, and normalization of tumor marker level. PR: >=30% decrease under baseline of the sum of the LD of all target lesions. CR and PR persist on repeat imaging study at least 4 weeks after initial documentation. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Reference is the smallest sum LD. PD was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of one or more new lesions and/or the unequivocal progression of existing non-target lesions.

ITT population included all participants randomized into the study. Number of participants analyzed (N) = participants with measurable disease at baseline.

Posted

Number

percentage of participants

ID	Title	Description
OG000	Bevacizumab + IFN-Alfa-2A	Bevacizumab infusions were administered every two weeks at a dose of 10 mg/kg for 52 weeks or until disease progression or unacceptable toxicity. IFN-Alfa-2A was administered 3 times per week as a subcutaneous injection at a dose of 9 MIU for 52 weeks or until disease progression or major toxicity.

Secondary

Change From Baseline in Karnofsky Performance Status

Karnofsky performance score is used to quantify participant's general well-being and activities of daily life and participants were classified based on their functional impairment. Karnofsky performance score is 11 level score which ranges between 0 (death) to 100 (no evidence of disease). Higher score means higher ability to perform daily tasks.

Safety population: all participants randomized and exposed to study drug (8 randomized participants did not receive study treatment and were not included, 2 in bevacizumab and 6 in placebo group). 12 participants randomized to placebo received bevacizumab, were included in bevacizumab arm. n=number of evaluable participants at specified time point.

Posted

Median

Full Range

score on a scale

Baseline, Week 7, 15, 23, 31, 43

ID	Title	Description
OG000	Bevacizumab + IFN-Alfa-2A	Bevacizumab infusions were administered every two weeks at a dose of 10 mg/kg for 52 weeks or until disease progression or unacceptable toxicity. IFN-Alfa-2A was administered 3 times per week as a subcutaneous injection at a dose of 9 MIU for 52 weeks or until disease progression or major toxicity.
OG001	Placebo + IFN-Alfa-2A	Placebo matched with Bevacizumab infusions were administered every two weeks for 52 weeks or until disease progression or unacceptable toxicity. IFN-Alfa-2A was administered 3 times per week as a subcutaneous injection at a dose of 9 MIU for 52 weeks or until disease progression or major toxicity.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Bevacizumab + IFN-Alfa-2A	Bevacizumab infusions were administered every two weeks at a dose of 10 mg/kg for 52 weeks or until disease progression or unacceptable toxicity. IFN-Alfa-2A was administered 3 times per week as a subcutaneous injection at a dose of 9 MIU for 52 weeks or until disease progression or major toxicity.			103	337	319	337
EG001	Placebo + IFN-Alfa-2A	Placebo matched with Bevacizumab infusions were administered every two weeks for 52 weeks or until disease progression or unacceptable toxicity. IFN-Alfa-2A was administered 3 times per week as a subcutaneous injection at a dose of 9 MIU for 52 weeks or until disease progression or major toxicity.			51	304	279	304

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Pneumonia	Infections and infestations	MedDRA version 11.1	Non-systematic Assessment	EG0008 affected337 at risk EG0010 affected304 at risk
Gastroenteritis	Infections and infestations	MedDRA version 11.1	Non-systematic Assessment	EG0003 affected337 at risk EG0011 affected304 at risk
Urinary tract infection	Infections and infestations	MedDRA version 11.1	Non-systematic Assessment	EG0002 affected337 at risk EG0011 affected304 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA version 11.1	Non-systematic Assessment	EG0000 affected337 at risk EG0012 affected304 at risk
Infection anal abscess	Infections and infestations	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Bronchopneumonia	Infections and infestations	MedDRA version 11.1	Non-systematic Assessment	EG0000 affected337 at risk EG0011 affected304 at risk
Gastroenteritis salmonella	Infections and infestations	MedDRA version 11.1	Non-systematic Assessment	EG0000 affected337 at risk EG0011 affected304 at risk
Hepatitis C	Infections and infestations	MedDRA version 11.1	Non-systematic Assessment	EG0000 affected337 at risk EG0011 affected304 at risk
Infection	Infections and infestations	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Labyrinthitis	Infections and infestations	MedDRA version 11.1	Non-systematic Assessment	EG0000 affected337 at risk EG0011 affected304 at risk
Localised infection	Infections and infestations	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Postoperative abscess	Infections and infestations	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Rectal abscess	Infections and infestations	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Renal abscess	Infections and infestations	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Sepsis	Infections and infestations	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Sinusitis	Infections and infestations	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Staphylococcal sepsis	Infections and infestations	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Urosepsis	Infections and infestations	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Viral infection	Infections and infestations	MedDRA version 11.1	Non-systematic Assessment	EG0000 affected337 at risk EG0011 affected304 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA version 11.1	Non-systematic Assessment	EG0003 affected337 at risk EG0012 affected304 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA version 11.1	Non-systematic Assessment	EG0002 affected337 at risk EG0011 affected304 at risk
Constipation	Gastrointestinal disorders	MedDRA version 11.1	Non-systematic Assessment	EG0002 affected337 at risk EG0010 affected304 at risk
Small intestinal haemorrhage	Gastrointestinal disorders	MedDRA version 11.1	Non-systematic Assessment	EG0002 affected337 at risk EG0010 affected304 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0011 affected304 at risk
Vomiting	Gastrointestinal disorders	MedDRA version 11.1	Non-systematic Assessment	EG0002 affected337 at risk EG0010 affected304 at risk
Ascites	Gastrointestinal disorders	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Colitis	Gastrointestinal disorders	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Duodenal perforation	Gastrointestinal disorders	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Gastric perforation	Gastrointestinal disorders	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Gastric ulcer haemorrhage	Gastrointestinal disorders	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Gingival bleeding	Gastrointestinal disorders	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Inguinal hernia	Gastrointestinal disorders	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Intestinal perforation	Gastrointestinal disorders	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Large intestine perforation	Gastrointestinal disorders	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Nausea	Gastrointestinal disorders	MedDRA version 11.1	Non-systematic Assessment	EG0000 affected337 at risk EG0011 affected304 at risk
Subileus	Gastrointestinal disorders	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Fatigue	General disorders	MedDRA version 11.1	Non-systematic Assessment	EG0007 affected337 at risk EG0010 affected304 at risk
Pyrexia	General disorders	MedDRA version 11.1	Non-systematic Assessment	EG0005 affected337 at risk EG0010 affected304 at risk
Asthenia	General disorders	MedDRA version 11.1	Non-systematic Assessment	EG0002 affected337 at risk EG0012 affected304 at risk
General physical health	General disorders	MedDRA version 11.1	Non-systematic Assessment	EG0002 affected337 at risk EG0010 affected304 at risk
Deterioration pain	General disorders	MedDRA version 11.1	Non-systematic Assessment	EG0000 affected337 at risk EG0012 affected304 at risk
Adverse drug reaction	General disorders	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Chills	General disorders	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Death	General disorders	MedDRA version 11.1	Non-systematic Assessment	EG0000 affected337 at risk EG0011 affected304 at risk
Injection site reaction	General disorders	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Malaise	General disorders	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Necrosis	General disorders	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Headache	Nervous system disorders	MedDRA version 11.1	Non-systematic Assessment	EG0002 affected337 at risk EG0011 affected304 at risk
Epilepsy	Nervous system disorders	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0011 affected304 at risk
Syncope	Nervous system disorders	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0011 affected304 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA version 11.1	Non-systematic Assessment	EG0002 affected337 at risk EG0010 affected304 at risk
Cerebral ischaemia	Nervous system disorders	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Encephalopathy	Nervous system disorders	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Gliosis	Nervous system disorders	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Haemorrhage intracranial	Nervous system disorders	MedDRA version 11.1	Non-systematic Assessment	EG0000 affected337 at risk EG0011 affected304 at risk
Hyperaesthesia	Nervous system disorders	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Lethargy	Nervous system disorders	MedDRA version 11.1	Non-systematic Assessment	EG0000 affected337 at risk EG0011 affected304 at risk
Leukoencephalopathy	Nervous system disorders	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Movement disorder	Nervous system disorders	MedDRA version 11.1	Non-systematic Assessment	EG0000 affected337 at risk EG0011 affected304 at risk
Nervous system disorder	Nervous system disorders	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Paraesthesia	Nervous system disorders	MedDRA version 11.1	Non-systematic Assessment	EG0000 affected337 at risk EG0011 affected304 at risk
Psychomotor hyperactivity	Nervous system disorders	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Somnolence	Nervous system disorders	MedDRA version 11.1	Non-systematic Assessment	EG0000 affected337 at risk EG0011 affected304 at risk
Spinal cord compression	Nervous system disorders	MedDRA version 11.1	Non-systematic Assessment	EG0000 affected337 at risk EG0011 affected304 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA version 11.1	Non-systematic Assessment	EG0005 affected337 at risk EG0011 affected304 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA version 11.1	Non-systematic Assessment	EG0003 affected337 at risk EG0010 affected304 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA version 11.1	Non-systematic Assessment	EG0003 affected337 at risk EG0010 affected304 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA version 11.1	Non-systematic Assessment	EG0002 affected337 at risk EG0010 affected304 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0011 affected304 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA version 11.1	Non-systematic Assessment	EG0000 affected337 at risk EG0011 affected304 at risk
Pulmonary congestion	Respiratory, thoracic and mediastinal disorders	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Confusional state	Psychiatric disorders	MedDRA version 11.1	Non-systematic Assessment	EG0003 affected337 at risk EG0013 affected304 at risk
Depression	Psychiatric disorders	MedDRA version 11.1	Non-systematic Assessment	EG0004 affected337 at risk EG0012 affected304 at risk
Anxiety	Psychiatric disorders	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Mood altered	Psychiatric disorders	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA version 11.1	Non-systematic Assessment	EG0004 affected337 at risk EG0015 affected304 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA version 11.1	Non-systematic Assessment	EG0002 affected337 at risk EG0010 affected304 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA version 11.1	Non-systematic Assessment	EG0003 affected337 at risk EG0011 affected304 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA version 11.1	Non-systematic Assessment	EG0002 affected337 at risk EG0011 affected304 at risk
Cachexia	Metabolism and nutrition disorders	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA version 11.1	Non-systematic Assessment	EG0000 affected337 at risk EG0011 affected304 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA version 11.1	Non-systematic Assessment	EG0000 affected337 at risk EG0011 affected304 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA version 11.1	Non-systematic Assessment	EG0000 affected337 at risk EG0011 affected304 at risk
Hypertension	Vascular disorders	MedDRA version 11.1	Non-systematic Assessment	EG0003 affected337 at risk EG0010 affected304 at risk
Hypotension	Vascular disorders	MedDRA version 11.1	Non-systematic Assessment	EG0000 affected337 at risk EG0012 affected304 at risk
Aneurysm ruptured	Vascular disorders	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Aortic aneurysm	Vascular disorders	MedDRA version 11.1	Non-systematic Assessment	EG0000 affected337 at risk EG0011 affected304 at risk
Deep vein thrombosis	Vascular disorders	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Hypertensive crisis	Vascular disorders	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Venous thrombosis	Vascular disorders	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Pathological fracture	Musculoskeletal and connective tissue disorders	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0012 affected304 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA version 11.1	Non-systematic Assessment	EG0002 affected337 at risk EG0010 affected304 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Chondrocalcinosis	Musculoskeletal and connective tissue disorders	MedDRA version 11.1	Non-systematic Assessment	EG0000 affected337 at risk EG0011 affected304 at risk
Pyrophosphate muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Soft tissue necrosis	Musculoskeletal and connective tissue disorders	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Haematuria	Renal and urinary disorders	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Hydronephrosis	Renal and urinary disorders	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Nephritic syndrome	Renal and urinary disorders	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Proteinuria	Renal and urinary disorders	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Renal failure	Renal and urinary disorders	MedDRA version 11.1	Non-systematic Assessment	EG0000 affected337 at risk EG0011 affected304 at risk
Renal failure acute	Renal and urinary disorders	MedDRA version 11.1	Non-systematic Assessment	EG0000 affected337 at risk EG0011 affected304 at risk
Renal impairment	Renal and urinary disorders	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Renal tubular necrosis	Renal and urinary disorders	MedDRA version 11.1	Non-systematic Assessment	EG0000 affected337 at risk EG0011 affected304 at risk
Metastatic pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0011 affected304 at risk
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 11.1	Non-systematic Assessment	EG0000 affected337 at risk EG0012 affected304 at risk
Benign penile neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Rectal cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Squamous cell carcinoma of skin	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA version 11.1	Non-systematic Assessment	EG0000 affected337 at risk EG0011 affected304 at risk
Medical device complication	Injury, poisoning and procedural complications	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Overdose	Injury, poisoning and procedural complications	MedDRA version 11.1	Non-systematic Assessment	EG0000 affected337 at risk EG0011 affected304 at risk
Postoperative wound	Injury, poisoning and procedural complications	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Complication traumatic haematoma	Injury, poisoning and procedural complications	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Upper limb fracture	Injury, poisoning and procedural complications	MedDRA version 11.1	Non-systematic Assessment	EG0000 affected337 at risk EG0011 affected304 at risk
Atrial fibrillation	Cardiac disorders	MedDRA version 11.1	Non-systematic Assessment	EG0003 affected337 at risk EG0011 affected304 at risk
Myocardial infarction	Cardiac disorders	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA version 11.1	Non-systematic Assessment	EG0002 affected337 at risk EG0010 affected304 at risk
Eczema	Skin and subcutaneous tissue disorders	MedDRA version 11.1	Non-systematic Assessment	EG0000 affected337 at risk EG0011 affected304 at risk
Skin graft failure	Skin and subcutaneous tissue disorders	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Hepatic failure	Hepatobiliary disorders	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Jaundice	Hepatobiliary disorders	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Adrenal insufficiency	Endocrine disorders	MedDRA version 11.1	Non-systematic Assessment	EG0000 affected337 at risk EG0011 affected304 at risk
Hypercalcaemia of malignancy	Endocrine disorders	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk
Hydrocele	Congenital, familial and genetic disorders	MedDRA version 11.1	Non-systematic Assessment	EG0000 affected337 at risk EG0011 affected304 at risk
Retinal vein thrombosis	Eye disorders	MedDRA version 11.1	Non-systematic Assessment	EG0000 affected337 at risk EG0011 affected304 at risk
Benign prostatic hyperplasia	Reproductive system and breast disorders	MedDRA version 11.1	Non-systematic Assessment	EG0000 affected337 at risk EG0011 affected304 at risk
Intestinal ischaemia	Gastrointestinal disorders	MedDRA version 11.1	Non-systematic Assessment	EG0001 affected337 at risk EG0010 affected304 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Pyrexia	General disorders	MedDRA version 11.1	Non-systematic Assessment	EG000149 affected337 at risk EG001130 affected304 at risk
Asthenia	General disorders	MedDRA version 11.1	Non-systematic Assessment	EG000108 affected337 at risk EG00183 affected304 at risk
Fatigue	General disorders	MedDRA version 11.1	Non-systematic Assessment	EG000107 affected337 at risk EG00183 affected304 at risk
Influenza like illness	General disorders	MedDRA version 11.1	Non-systematic Assessment	EG00084 affected337 at risk EG00178 affected304 at risk
Chills	General disorders	MedDRA version 11.1	Non-systematic Assessment	EG00053 affected337 at risk EG00154 affected304 at risk
Mucosal inflammation	General disorders	MedDRA version 11.1	Non-systematic Assessment	EG00018 affected337 at risk EG00111 affected304 at risk
Nausea	Gastrointestinal disorders	MedDRA version 11.1	Non-systematic Assessment	EG00097 affected337 at risk EG00178 affected304 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA version 11.1	Non-systematic Assessment	EG00070 affected337 at risk EG00148 affected304 at risk
Vomiting	Gastrointestinal disorders	MedDRA version 11.1	Non-systematic Assessment	EG00047 affected337 at risk EG00142 affected304 at risk
Constipation	Gastrointestinal disorders	MedDRA version 11.1	Non-systematic Assessment	EG00039 affected337 at risk EG00125 affected304 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA version 11.1	Non-systematic Assessment	EG00028 affected337 at risk EG00125 affected304 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA version 11.1	Non-systematic Assessment	EG00023 affected337 at risk EG00113 affected304 at risk
Stomatitis	Gastrointestinal disorders	MedDRA version 11.1	Non-systematic Assessment	EG00017 affected337 at risk EG0015 affected304 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA version 11.1	Non-systematic Assessment	EG00063 affected337 at risk EG00141 affected304 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA version 11.1	Non-systematic Assessment	EG00033 affected337 at risk EG00128 affected304 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA version 11.1	Non-systematic Assessment	EG00038 affected337 at risk EG00119 affected304 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA version 11.1	Non-systematic Assessment	EG00026 affected337 at risk EG00121 affected304 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA version 11.1	Non-systematic Assessment	EG00023 affected337 at risk EG00115 affected304 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA version 11.1	Non-systematic Assessment	EG00025 affected337 at risk EG00113 affected304 at risk
Anorexia	Metabolism and nutrition disorders	MedDRA version 11.1	Non-systematic Assessment	EG000122 affected337 at risk EG00193 affected304 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA version 11.1	Non-systematic Assessment	EG00090 affected337 at risk EG00111 affected304 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA version 11.1	Non-systematic Assessment	EG00045 affected337 at risk EG00138 affected304 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA version 11.1	Non-systematic Assessment	EG00034 affected337 at risk EG00139 affected304 at risk
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA version 11.1	Non-systematic Assessment	EG00017 affected337 at risk EG0010 affected304 at risk
Headache	Nervous system disorders	MedDRA version 11.1	Non-systematic Assessment	EG00082 affected337 at risk EG00150 affected304 at risk
Dizziness	Nervous system disorders	MedDRA version 11.1	Non-systematic Assessment	EG00027 affected337 at risk EG00127 affected304 at risk
Dysgeusia	Nervous system disorders	MedDRA version 11.1	Non-systematic Assessment	EG00021 affected337 at risk EG00113 affected304 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA version 11.1	Non-systematic Assessment	EG00032 affected337 at risk EG00123 affected304 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA version 11.1	Non-systematic Assessment	EG00030 affected337 at risk EG00120 affected304 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA version 11.1	Non-systematic Assessment	EG00024 affected337 at risk EG00119 affected304 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA version 11.1	Non-systematic Assessment	EG00017 affected337 at risk EG00121 affected304 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA version 11.1	Non-systematic Assessment	EG00033 affected337 at risk EG00139 affected304 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA version 11.1	Non-systematic Assessment	EG00023 affected337 at risk EG00121 affected304 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA version 11.1	Non-systematic Assessment	EG00021 affected337 at risk EG00113 affected304 at risk
Hypertension	Vascular disorders	MedDRA version 11.1	Non-systematic Assessment	EG00095 affected337 at risk EG00127 affected304 at risk
Depression	Psychiatric disorders	MedDRA version 11.1	Non-systematic Assessment	EG00038 affected337 at risk EG00130 affected304 at risk
Insomnia	Psychiatric disorders	MedDRA version 11.1	Non-systematic Assessment	EG00021 affected337 at risk EG00120 affected304 at risk
Anxiety	Psychiatric disorders	MedDRA version 11.1	Non-systematic Assessment	EG0009 affected337 at risk EG00118 affected304 at risk
Weight decreased	Investigations	MedDRA version 11.1	Non-systematic Assessment	EG00068 affected337 at risk EG00144 affected304 at risk
Proteinuria	Renal and urinary disorders	MedDRA version 11.1	Non-systematic Assessment	EG00068 affected337 at risk EG0019 affected304 at risk

Ancestor Terms

ID	Term
D000230	Adenocarcinoma
D002277	Carcinoma
D009375	Neoplasms, Glandular and Epithelial
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D007680	Kidney Neoplasms
D014571	Urologic Neoplasms
D014565	Urogenital Neoplasms
D009371	Neoplasms by Site
D052776	Female Urogenital Diseases
D005261	Female Urogenital Diseases and Pregnancy Complications
D000091642	Urogenital Diseases
D007674	Kidney Diseases
D014570	Urologic Diseases
D052801	Male Urogenital Diseases

Ancestor Terms

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
D016898	Interferon-alpha
D007370	Interferon Type I
D007372	Interferons
D016207	Cytokines
D036341	Intercellular Signaling Peptides and Proteins
D010455	Peptides
D001685	Biological Factors

Placebo matched with Bevacizumab infusions were administered every two weeks for 52 weeks or until disease progression or unacceptable toxicity. IFN-Alfa-2A was administered 3 times per week as a subcutaneous injection at a dose of 9 MIU for 52 weeks or until disease progression or major toxicity.

Facility	Status	City	State	ZIP	Country	Contacts
		Adelaide		5011	Australia