Carboplatin and Paclitaxel With or Without Bevacizumab in Treating Patients With Stage III or Stage IV Ovarian Epithelial, Primary Peritoneal, or Fallopian Tube Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.

ClinicalTrials.gov Identifier: NCT00262847

Recruitment Status : Completed

First Posted : December 7, 2005

Results First Posted : September 18, 2013

Last Update Posted : July 23, 2019

View this study on the modernized ClinicalTrials.gov

Sponsor:

Collaborator:

NRG Oncology

Information provided by (Responsible Party):

National Cancer Institute (NCI)

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
Conditions	Fallopian Tube Clear Cell Adenocarcinoma Fallopian Tube Endometrioid Adenocarcinoma Fallopian Tube Mucinous Adenocarcinoma Fallopian Tube Serous Adenocarcinoma Fallopian Tube Transitional Cell Carcinoma Malignant Ovarian Mixed Epithelial Tumor Ovarian Brenner Tumor Ovarian Clear Cell Adenocarcinoma Ovarian Endometrioid Adenocarcinoma Ovarian Mucinous Adenocarcinoma Ovarian Serous Adenocarcinoma Ovarian Transitional Cell Carcinoma Primary Peritoneal Serous Adenocarcinoma Stage IIIA Fallopian Tube Cancer Stage IIIA Ovarian Cancer Stage IIIA Primary Peritoneal Cancer Stage IIIB Fallopian Tube Cancer Stage IIIB Ovarian Cancer Stage IIIB Primary Peritoneal Cancer Stage IIIC Fallopian Tube Cancer Stage IIIC Ovarian Cancer Stage IIIC Primary Peritoneal Cancer Stage IV Fallopian Tube Cancer Stage IV Ovarian Cancer Stage IV Primary Peritoneal Cancer Undifferentiated Fallopian Tube Carcinoma Undifferentiated Ovarian Carcinoma
Interventions	Biological: Bevacizumab Drug: Carboplatin Other: Laboratory Biomarker Analysis Drug: Paclitaxel Other: Placebo Other: Quality-of-Life Assessment
Enrollment	1873

Participant Flow

Recruitment Details	Between October 2005 and June 2009, 1873 women were enrolled from 336 institutions in the United States, Canada, South Korea, and Japan.
Pre-assignment Details


Arm/Group Title	Arm I (Placebo, Paclitaxel, Carboplatin)	Arm II (Placebo, Paclitaxel, Carboplatin, Bevacizumab)	Arm III (Paclitaxel, Carboplatin, Bevacizumab)
Arm/Group Description	Control therapy: ...	Bevacizumab-initiation therapy: ...	Bevacizumab-throughout therapy: ...
Arm/Group Description	Control therapy: Cycles 1-6 received paclitaxel, 175 mg/m2 plus carboplatin AUC 6 plus placebo (starting in cycle 2) every 3 weeks. Cycles 7-22 received placebo every 3 weeks.	Bevacizumab-initiation therapy: Cycles 1-6 received paclitaxel, 175 mg/m2 plus carboplatin AUC 6 plus bevacizumab, 15 mg/kg (starting in cycle 2) every 3 weeks. Cycles 7-22 received placebo every 3 weeks.	Bevacizumab-throughout therapy: Cycles 1-6 received paclitaxel, 175 mg/m2 plus carboplatin AUC 6 plus bevacizumab, 15 mg/kg (starting in cycle 2) every 3 weeks. Cycles 7-22 received bevacizumab, 15 mg/kg every 3 weeks.
Period Title: Overall Study
Started	625 ^[1]	625 ^[1]	623 ^[1]
Completed	107	112	227
Not Completed	518	513	396
Reason Not Completed
Disease Progression	309	274	195
Patient Refusal	41	52	47
Adverse Event	74	88	108
Death	8	8	11
Concomitant disease	3	2	4
Other Reasons	79	88	27
Did not receive study treatment	4	1	4
[1] Total enrolled and included in efficacy analysis

Baseline Characteristics

Arm/Group Title		Arm I (Placebo, Paclitaxel, Carboplatin)	Arm II (Placebo, Paclitaxel, Carboplatin, Bevacizumab)	Arm III (Paclitaxel, Carboplatin, Bevacizumab)	Total
Arm/Group Description		Control therapy: ...	Bevacizumab-initiation therapy: ...	Bevacizumab-throughout therapy: ...	Total of all reporting groups
Arm/Group Description		Control therapy: Cycles 1-6 received paclitaxel, 175 mg/m2 plus carboplatin AUC 6 plus placebo (starting in cycle 2) every 3 weeks. Cycles 7-22 received placebo every 3 weeks.	Bevacizumab-initiation therapy: Cycles 1-6 received paclitaxel, 175 mg/m2 plus carboplatin AUC 6 plus bevacizumab, 15 mg/kg (starting in cycle 2) every 3 weeks. Cycles 7-22 received placebo every 3 weeks.	Bevacizumab-throughout therapy: Cycles 1-6 received paclitaxel, 175 mg/m2 plus carboplatin AUC 6 plus bevacizumab, 15 mg/kg (starting in cycle 2) every 3 weeks. Cycles 7-22 received bevacizumab, 15 mg/kg every 3 weeks.	Total of all reporting groups
Overall Number of Baseline Participants		625	625	623	1873
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	625 participants	625 participants	623 participants	1873 participants
		59.3 (10.9)	60.1 (10.3)	59.7 (10.6)	59.7 (10.6)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	625 participants	625 participants	623 participants	1873 participants
	Female	625 100.0%	625 100.0%	623 100.0%	1873 100.0%
	Male	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Race/Ethnicity, Customized Measure Type: Number Unit of measure: Participant	Number Analyzed	625 participants	625 participants	623 participants	1873 participants
Non-Hispanic white		526	519	521	1566
Asian		41	37	39	117
Non-Hispanic black		25	28	27	80
Hispanic		21	28	25	74
Other or unspecified		12	13	11	36
Region of Enrollment Measure Type: Number Unit of measure: Participants	Number Analyzed	625 participants	625 participants	623 participants	1873 participants
United States		596	596	599	1791
Canada		1	5	3	9
Japan		21	12	12	45
Korea, Republic of		7	12	9	28
Gynecologic Oncology Group (GOG) Performance Status ^[1] Measure Type: Number Unit of measure: Participants	Number Analyzed	625 participants	625 participants	623 participants	1873 participants
0 - fully active		311	315	305	931
1 - restricted strenuous activity, ambulatory		272	270	267	809
2 - ambulatory, difficulty walking		42	40	51	133
3 - limited self-care, partly confined to bed		0	0	0	0
4 - completely disabled, no self-care		0	0	0	0
		[1] Measure Description: 5-point, ordinal scale specifying patient's ability to perform activities from 0(fully active) to 4(completely disabled, no self-care).
International Federation of Gynecologic and Obstetrics (FIGO) Stage ^[1] Measure Type: Number Unit of measure: Participants	Number Analyzed	625 participants	625 participants	623 participants	1873 participants
1-limited to ovaries		0	0	0	0
1A-1 ovary involved, no ascites		0	0	0	0
1B-both ovaries involved, no ascites		0	0	0	0
1C-disease with capsules ruptured or ascites		0	0	0	0
2-disease with pelvic extension		0	0	0	0
2A-disease with extension to uterus and or tubes		0	0	0	0
2B-disease with extension to other pelvic tissues		0	0	0	0
2C-disease with capsules ruptured or ascites		0	0	0	0
3-disease w/ macroscopic implants outside pelvis		218	205	216	639
3-disease w/ implants > 1 cm outside pelvis		254	256	242	752
3A-disease w/ microscopic implants, negative nodes		0	0	0	0
3B-disease w/ abdominal implants <2cm, neg nodes		0	0	0	0
3C-disease w/ abdominal implants >2cm, pos nodes		0	0	0	0
4-distant metastatis		153	164	165	482
		[1] Measure Description: Clinical staging for primary carcinoma of the ovary (1985) from Stage 1 (limited to ovaries) to Stage 4 (distant metastatis)
Histologic Type ^[1] Measure Type: Number Unit of measure: Participants	Number Analyzed	625 participants	625 participants	623 participants	1873 participants
Serous adenocarcinoma		541	519	524	1584
Endometrioid		21	14	24	59
Clear cell		12	23	20	55
Mucinous		6	5	8	19
Other or not specified		45	64	47	156
		[1] Measure Description: Histologic(cell) type was obtained from the central GOG Pathology Committee review updated in September 2010.
Tumor Grade ^[1] Measure Type: Number Unit of measure: Participants	Number Analyzed	625 participants	625 participants	623 participants	1873 participants
3		445	465	460	1370
2		102	86	97	285
1		36	28	18	82
Not graded		42	46	48	136
		[1] Measure Description: Tumor grade was obtained from the central GOG Pathology Committee review updated in September 2010. All clear-cell tumors were classified as grade 3.

Outcome Measures

1.Primary Outcome


Title	Progression-free Survival
Description	Median progression-free survival (PFS). Onset of progression could be ...
Description	Median progression-free survival (PFS). Onset of progression could be based on radiographic (RECIST) criteria or rising CA-125 (GCIG criteria).
Time Frame	From study entry until first disease progression, death or date of last contact, up to 6 years

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Arm I (Placebo, Paclitaxel, Carboplatin)	Arm II (Placebo, Paclitaxel, Carboplatin, Bevacizumab)	Arm III (Paclitaxel, Carboplatin, Bevacizumab)
Arm/Group Description:	Control therapy: ...	Bevacizumab-initiation therapy: ...	Bevacizumab-throughout therapy: ...
Arm/Group Description:	Control therapy: Cycles 1-6 received paclitaxel, 175 mg/m2 plus carboplatin AUC 6 plus placebo (starting in cycle 2) every 3 weeks. Cycles 7-22 received placebo every 3 weeks.	Bevacizumab-initiation therapy: Cycles 1-6 received paclitaxel, 175 mg/m2 plus carboplatin AUC 6 plus bevacizumab, 15 mg/kg (starting in cycle 2) every 3 weeks. Cycles 7-22 received placebo every 3 weeks.	Bevacizumab-throughout therapy: Cycles 1-6 received paclitaxel, 175 mg/m2 plus carboplatin AUC 6 plus bevacizumab, 15 mg/kg (starting in cycle 2) every 3 weeks. Cycles 7-22 received bevacizumab, 15 mg/kg every 3 weeks.
Overall Number of Participants Analyzed	625	625	623
Median (95% Confidence Interval) Unit of Measure: months
	11.0 (10.2 to 12.0)	12.3 (11.4 to 12.8)	15.3 (14.2 to 16.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Placebo, Paclitaxel, Carboplatin), Arm II (Placebo, Paclitaxel, Carboplatin, Bevacizumab)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.448
	Comments	[Not Specified]
	Method	Regression, Cox
	Comments	Proportional Hazards model stratified by stage of disease and size of residual disease following initial staging surgery.

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.954
	Confidence Interval	95% 0.844 to 1.078
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arm I (Placebo, Paclitaxel, Carboplatin), Arm III (Paclitaxel, Carboplatin, Bevacizumab)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Regression, Cox
	Comments	Proportional Hazards model stratified by stage of disease and size of residual disease following initial staging surgery.

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.765
	Confidence Interval	95% 0.676 to 0.866
	Estimation Comments	[Not Specified]

2.Secondary Outcome


Title	Overall Survival
Description	Median overall survival (OS)
Description	Median overall survival (OS)
Time Frame	From study entry to death or last contact, up to 6 years

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Arm I (Placebo, Paclitaxel, Carboplatin)	Arm II (Placebo, Paclitaxel, Carboplatin, Bevacizumab)	Arm III (Paclitaxel, Carboplatin, Bevacizumab)
Arm/Group Description:	Control therapy: ...	Bevacizumab-initiation therapy: ...	Bevacizumab-throughout therapy: ...
Arm/Group Description:	Control therapy: Cycles 1-6 received paclitaxel, 175 mg/m2 plus carboplatin AUC 6 plus placebo (starting in cycle 2) every 3 weeks. Cycles 7-22 received placebo every 3 weeks.	Bevacizumab-initiation therapy: Cycles 1-6 received paclitaxel, 175 mg/m2 plus carboplatin AUC 6 plus bevacizumab, 15 mg/kg (starting in cycle 2) every 3 weeks. Cycles 7-22 received placebo every 3 weeks.	Bevacizumab-throughout therapy: Cycles 1-6 received paclitaxel, 175 mg/m2 plus carboplatin AUC 6 plus bevacizumab, 15 mg/kg (starting in cycle 2) every 3 weeks. Cycles 7-22 received bevacizumab, 15 mg/kg every 3 weeks.
Overall Number of Participants Analyzed	625	625	623
Median (95% Confidence Interval) Unit of Measure: months
	40.6 (37.1 to 45.5)	38.7 (35.2 to 42.1)	43.8 (39.7 to 49.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Placebo, Paclitaxel, Carboplatin), Arm II (Placebo, Paclitaxel, Carboplatin, Bevacizumab)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.410
	Comments	[Not Specified]
	Method	Regression, Cox
	Comments	Proportional Hazards model stratified by stage of disease and size of residual disease following initial staging surgery.

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.069
	Confidence Interval	95% 0.912 to 1.255
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arm I (Placebo, Paclitaxel, Carboplatin), Arm III (Paclitaxel, Carboplatin, Bevacizumab)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.131
	Comments	[Not Specified]
	Method	Regression, Cox
	Comments	Proportional Hazards model stratified by stage of disease and size of residual disease following initial staging surgery.

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.880
	Confidence Interval	95% 0.746 to 1.039
	Estimation Comments	[Not Specified]

3.Secondary Outcome


Title	Frequency and Severity (Grade 3 or Above) of Adverse Events Assessed by Common Terminology Criteria for Adverse Events Version 3.0
Description	Eligible and Evaluable patients
Description	Eligible and Evaluable patients
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

Eligible and evaluable patients


Arm/Group Title	Arm I Toxicities (Placebo, Paclitaxel, Carboplatin)	Arm II Toxicities (Placabo,Paclitaxel,Carboplatin,Bevacizumab)	Arm III Toxicities (Paclitaxel, Carboplatin, Bevacizumab)
Arm/Group Description:	Control therapy: ...	Bevacizumab-initiation therapy: ...	Bevacizumab-throughout therapy: ...
Arm/Group Description:	Control therapy: Cycles 1-6 received paclitaxel, 175 mg/m2 plus carboplatin AUC 6 plus placebo (starting in cycle 2) every 3 weeks. Cycles 7-22 received placebo every 3 weeks.	Bevacizumab-initiation therapy: Cycles 1-6 received paclitaxel, 175 mg/m2 plus carboplatin AUC 6 plus bevacizumab, 15 mg/kg (starting in cycle 2) every 3 weeks. Cycles 7-22 received placebo every 3 weeks.	Bevacizumab-throughout therapy: Cycles 1-6 received paclitaxel, 175 mg/m2 plus carboplatin AUC 6 plus bevacizumab, 15 mg/kg (starting in cycle 2) every 3 weeks. Cycles 7-22 received bevacizumab, 15 mg/kg every 3 weeks.
Overall Number of Participants Analyzed	621	624	619
Measure Type: Count of Participants Unit of Measure: Participants
White blood cell	317 51.0%	328 52.6%	327 52.8%
Absolute neutrophil count	540 87.0%	543 87.0%	536 86.6%
Hemoglobin	91 14.7%	86 13.8%	74 12.0%
Platelets	93 15.0%	122 19.6%	131 21.2%
Other hematologic	13 2.1%	13 2.1%	9 1.5%
Allergy/Immunology	23 3.7%	25 4.0%	14 2.3%
Auditory/Ear	1 0.2%	1 0.2%	2 0.3%
hypertension	10 1.6%	36 5.8%	65 10.5%
Cardiac	14 2.3%	12 1.9%	18 2.9%
Coagulation	5 0.8%	7 1.1%	8 1.3%
Constitutional	62 10.0%	61 9.8%	83 13.4%
Dermatologic	13 2.1%	20 3.2%	16 2.6%
Endocrine	4 0.6%	4 0.6%	2 0.3%
Gastrointestinal	96 15.5%	112 17.9%	122 19.7%
Genitourinary/Renal	13 2.1%	8 1.3%	8 1.3%
Hemorrhage	5 0.8%	9 1.4%	15 2.4%
Hepatobiliary	2 0.3%	1 0.2%	3 0.5%
Infection	75 12.1%	73 11.7%	95 15.3%
Lymphatics	4 0.6%	3 0.5%	3 0.5%
Metabolic	91 14.7%	87 13.9%	101 16.3%
Musculoskeletal	16 2.6%	17 2.7%	21 3.4%
Neurosensory	23 3.7%	26 4.2%	28 4.5%
Other neurological	44 7.1%	42 6.7%	65 10.5%
Ocular/Visual	4 0.6%	1 0.2%	4 0.6%
Pain	74 11.9%	82 13.1%	101 16.3%
Pulmonary	29 4.7%	36 5.8%	32 5.2%
Vascular	37 6.0%	33 5.3%	40 6.5%
Death, not CTC coded	5 0.8%	8 1.3%	10 1.6%
Sexual/Reproductive	1 0.2%	0 0.0%	0 0.0%

4.Secondary Outcome


Title	Impact on Quality of Life Measured by the Functional Assessment of Cancer Therapy-Ovary Trial Outcome Index (FACT-O TOI)
Description	Estimated least squares means from a mixed module of Quality of Life (...
Description	Estimated least squares means from a mixed module of Quality of Life (QOL) scores at each assessment point, adjusted for baseline score and patient's age. Note: The range of possible scores of the FACT-O TOI is 0 - 104 for all treatment groups and at all visits. A higher score indicates better QOL. Baseline mean scores are raw means.
Time Frame	At baseline, 9, 18, 36, 60, and 84 weeks

Outcome Measure Data

Analysis Population Description

Number of valid QOL assessments do not total number of patients randomized in study.


Arm/Group Title	Arm I (Placebo, Paclitaxel, Carboplatin)	Arm II (Placebo, Paclitaxel, Carboplatin, Bevacizumab)	Arm III (Paclitaxel, Carboplatin, Bevacizumab)
Arm/Group Description:	Control therapy: ...	Bevacizumab-initiation therapy: ...	Bevacizumab-throughout therapy: ...
Arm/Group Description:	Control therapy: Cycles 1-6 received paclitaxel, 175 mg/m2 plus carboplatin AUC 6 plus placebo (starting in cycle 2) every 3 weeks. Cycles 7-22 received placebo every 3 weeks.	Bevacizumab-initiation therapy: Cycles 1-6 received paclitaxel, 175 mg/m2 plus carboplatin AUC 6 plus bevacizumab, 15 mg/kg (starting in cycle 2) every 3 weeks. Cycles 7-22 received placebo every 3 weeks.	Bevacizumab-throughout therapy: Cycles 1-6 received paclitaxel, 175 mg/m2 plus carboplatin AUC 6 plus bevacizumab, 15 mg/kg (starting in cycle 2) every 3 weeks. Cycles 7-22 received bevacizumab, 15 mg/kg every 3 weeks.
Overall Number of Participants Analyzed	625	625	623
Least Squares Mean (Standard Deviation) Unit of Measure: units on a scale
prior to treatment	68.2 (0.64)	68.0 (0.66)	67.4 (0.65)
prior to cycle 4	73.8 (0.53)	71.1 (0.56)	70.9 (0.54)
prior to cycle 7	76.0 (0.54)	74.3 (0.56)	73.8 (0.58)
prior to cycle 13	80.6 (0.62)	80.5 (0.62)	79.9 (0.58)
prior to cycle 21	77.6 (0.73)	79.1 (0.71)	78.6 (0.66)
6 months followup	75.8 (0.78)	77.6 (0.75)	77.8 (0.75)

Adverse Events

Time Frame	All Adverse Events(AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adeverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Adverse Event Reporting Description	[Not Specified]

Arm/Group Title	Arm I (Placebo, Paclitaxel, Carboplatin)	Arm II (Placebo, Paclitaxel, Carboplatin, Bevacizumab)	Arm III (Paclitaxel, Carboplatin, Bevacizumab)
Arm/Group Description	Control therapy: ...	Bevacizumab-initiation therapy: ...	Bevacizumab-throughout therapy: ...
Arm/Group Description	Control therapy: Cycles 1-6 received paclitaxel, 175 mg/m2 plus carboplatin AUC 6 plus placebo (starting in cycle 2) every 3 weeks. Cycles 7-22 received placebo every 3 weeks.	Bevacizumab-initiation therapy: Cycles 1-6 received paclitaxel, 175 mg/m2 plus carboplatin AUC 6 plus bevacizumab, 15 mg/kg (starting in cycle 2) every 3 weeks. Cycles 7-22 received placebo every 3 weeks.	Bevacizumab-throughout therapy: Cycles 1-6 received paclitaxel, 175 mg/m2 plus carboplatin AUC 6 plus bevacizumab, 15 mg/kg (starting in cycle 2) every 3 weeks. Cycles 7-22 received bevacizumab, 15 mg/kg every 3 weeks.
All-Cause Mortality
	Arm I (Placebo, Paclitaxel, Carboplatin)	Arm II (Placebo, Paclitaxel, Carboplatin, Bevacizumab)	Arm III (Paclitaxel, Carboplatin, Bevacizumab)
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--	--/--
Serious Adverse Events Serious Adverse Events
	Arm I (Placebo, Paclitaxel, Carboplatin)	Arm II (Placebo, Paclitaxel, Carboplatin, Bevacizumab)	Arm III (Paclitaxel, Carboplatin, Bevacizumab)
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	239/621 (38.49%)	257/624 (41.19%)	287/619 (46.37%)
Blood and lymphatic system disorders
Myelodysplasia ^† 1	0/621 (0.00%)	1/624 (0.16%)	1/619 (0.16%)
Neutrophils ^† 1	14/621 (2.25%)	15/624 (2.40%)	13/619 (2.10%)
Platelets ^† 1	1/621 (0.16%)	2/624 (0.32%)	0/619 (0.00%)
Leukocytes ^† 1	1/621 (0.16%)	2/624 (0.32%)	3/619 (0.48%)
Hemoglobin ^† 1	3/621 (0.48%)	2/624 (0.32%)	1/619 (0.16%)
Lymphocele ^† 1	1/621 (0.16%)	0/624 (0.00%)	1/619 (0.16%)
Cardiac disorders
S/N Arrhythmia: Atrial Fibrillation ^† 1	3/621 (0.48%)	0/624 (0.00%)	1/619 (0.16%)
Cardiac Arrhythmia - Other ^† 1	1/621 (0.16%)	0/624 (0.00%)	0/619 (0.00%)
S/N Arrhythmia: Atrial Flutter ^† 1	1/621 (0.16%)	0/624 (0.00%)	0/619 (0.00%)
Vasovagal Episode ^† 1	0/621 (0.00%)	0/624 (0.00%)	1/619 (0.16%)
Supraventricular Tachycardia ^† 1	0/621 (0.00%)	0/624 (0.00%)	2/619 (0.32%)
S/N Arrhythmia:supraventricular Nos ^† 1	0/621 (0.00%)	1/624 (0.16%)	0/619 (0.00%)
S/N Arrhythmia: Sinus Bradycardia ^† 1	1/621 (0.16%)	0/624 (0.00%)	0/619 (0.00%)
Cardiac Ischemia/Infarction ^† 1	2/621 (0.32%)	2/624 (0.32%)	1/619 (0.16%)
Hypertension ^† 1	0/621 (0.00%)	4/624 (0.64%)	5/619 (0.81%)
Left Venticular Diastolic Dysfunction ^† 1	0/621 (0.00%)	0/624 (0.00%)	1/619 (0.16%)
Cardiac General - Other ^† 1	0/621 (0.00%)	1/624 (0.16%)	0/619 (0.00%)
Cardiac Troponin I (Ctni) ^† 1	0/621 (0.00%)	1/624 (0.16%)	0/619 (0.00%)
Hypotension ^† 1	1/621 (0.16%)	0/624 (0.00%)	2/619 (0.32%)
Endocrine disorders
Endocrine - Other ^† 1	0/621 (0.00%)	0/624 (0.00%)	1/619 (0.16%)
Eye disorders
Cataract ^† 1	0/621 (0.00%)	0/624 (0.00%)	2/619 (0.32%)
Gastrointestinal disorders
Fistula, Gi - Colon/Cecum/Appendix ^† 1	1/621 (0.16%)	2/624 (0.32%)	1/619 (0.16%)
Obstruction, Gi - Ileum ^† 1	0/621 (0.00%)	0/624 (0.00%)	1/619 (0.16%)
Necrosis, Gi - Small Bowel Nos ^† 1	0/621 (0.00%)	1/624 (0.16%)	0/619 (0.00%)
Perforation, Gi - Colon ^† 1	0/621 (0.00%)	4/624 (0.64%)	4/619 (0.65%)
Fistula, Gi - Ileum ^† 1	1/621 (0.16%)	0/624 (0.00%)	0/619 (0.00%)
Fistula, Gi - Small Bowel Nos ^† 1	0/621 (0.00%)	2/624 (0.32%)	1/619 (0.16%)
Fistula, Gi - Rectum ^† 1	1/621 (0.16%)	1/624 (0.16%)	1/619 (0.16%)
Obstruction, Gi - Colon ^† 1	2/621 (0.32%)	0/624 (0.00%)	1/619 (0.16%)
Gastritis ^† 1	0/621 (0.00%)	1/624 (0.16%)	0/619 (0.00%)
Hemorrhoids ^† 1	0/621 (0.00%)	1/624 (0.16%)	0/619 (0.00%)
Mucositis (Functional/Sympt) - Esophagus ^† 1	0/621 (0.00%)	0/624 (0.00%)	1/619 (0.16%)
Leak, Gi - Large Bowel ^† 1	0/621 (0.00%)	0/624 (0.00%)	1/619 (0.16%)
Perforation, Gi - Rectum ^† 1	1/621 (0.16%)	0/624 (0.00%)	0/619 (0.00%)
Leak, Gi - Rectum ^† 1	0/621 (0.00%)	0/624 (0.00%)	1/619 (0.16%)
Ileus ^† 1	5/621 (0.81%)	8/624 (1.28%)	3/619 (0.48%)
Fistula, Gi - Abdomen Nos ^† 1	0/621 (0.00%)	0/624 (0.00%)	1/619 (0.16%)
Obstruction, Gi - Duodenal ^† 1	0/621 (0.00%)	1/624 (0.16%)	0/619 (0.00%)
Obstruction, Gi - Small Bowel Nos ^† 1	13/621 (2.09%)	13/624 (2.08%)	15/619 (2.42%)
Colitis ^† 1	3/621 (0.48%)	1/624 (0.16%)	5/619 (0.81%)
Obstruction, Gi - Jejunum ^† 1	0/621 (0.00%)	1/624 (0.16%)	0/619 (0.00%)
Perforation, Gi - Small Bowel Nos ^† 1	1/621 (0.16%)	1/624 (0.16%)	1/619 (0.16%)
Vomiting ^† 1	12/621 (1.93%)	9/624 (1.44%)	6/619 (0.97%)
Anorexia ^† 1	2/621 (0.32%)	0/624 (0.00%)	0/619 (0.00%)
Dehydration ^† 1	9/621 (1.45%)	10/624 (1.60%)	11/619 (1.78%)
Constipation ^† 1	4/621 (0.64%)	4/624 (0.64%)	3/619 (0.48%)
Nausea ^† 1	4/621 (0.64%)	3/624 (0.48%)	5/619 (0.81%)
Gastrointestinal - Other ^† 1	1/621 (0.16%)	2/624 (0.32%)	1/619 (0.16%)
Diarrhea ^† 1	5/621 (0.81%)	3/624 (0.48%)	7/619 (1.13%)
Prolapse Of Stoma, Gi ^† 1	1/621 (0.16%)	0/624 (0.00%)	0/619 (0.00%)
General disorders
Fever ^† 1	3/621 (0.48%)	2/624 (0.32%)	5/619 (0.81%)
Fatigue ^† 1	1/621 (0.16%)	4/624 (0.64%)	2/619 (0.32%)
Death No Ctcae Term - Disease Progression Nos ^† 1	0/621 (0.00%)	4/624 (0.64%)	1/619 (0.16%)
Death No Ctcae Term - Death Nos ^† 1	0/621 (0.00%)	0/624 (0.00%)	2/619 (0.32%)
Death No Ctcae Term - Multi-Organ Failure ^† 1	1/621 (0.16%)	0/624 (0.00%)	0/619 (0.00%)
Death No Ctcae Term - Sudden Death ^† 1	1/621 (0.16%)	2/624 (0.32%)	2/619 (0.32%)
Pain - Other ^† 1	0/621 (0.00%)	1/624 (0.16%)	1/619 (0.16%)
Pain: Pelvis ^† 1	0/621 (0.00%)	1/624 (0.16%)	1/619 (0.16%)
Pain: Chest /Thorax Nos ^† 1	1/621 (0.16%)	1/624 (0.16%)	4/619 (0.65%)
Pain: Chest Wall ^† 1	0/621 (0.00%)	1/624 (0.16%)	0/619 (0.00%)
Pain: Pleura ^† 1	0/621 (0.00%)	1/624 (0.16%)	0/619 (0.00%)
Pain: Head/Headache ^† 1	1/621 (0.16%)	1/624 (0.16%)	0/619 (0.00%)
Pain: Intestine ^† 1	1/621 (0.16%)	0/624 (0.00%)	0/619 (0.00%)
Pain: Back ^† 1	0/621 (0.00%)	1/624 (0.16%)	1/619 (0.16%)
Pain: Joint ^† 1	1/621 (0.16%)	0/624 (0.00%)	0/619 (0.00%)
Pain: Bone ^† 1	0/621 (0.00%)	0/624 (0.00%)	1/619 (0.16%)
Pain: Kidney ^† 1	1/621 (0.16%)	0/624 (0.00%)	0/619 (0.00%)
Pain: Pain Nos ^† 1	1/621 (0.16%)	0/624 (0.00%)	0/619 (0.00%)
Pain: Rectum ^† 1	2/621 (0.32%)	1/624 (0.16%)	0/619 (0.00%)
Pain: Abdominal Pain Nos ^† 1	8/621 (1.29%)	8/624 (1.28%)	12/619 (1.94%)
Pain: Muscle ^† 1	0/621 (0.00%)	0/624 (0.00%)	1/619 (0.16%)
Hepatobiliary disorders
Hepatobiliary/Pancreas - Other ^† 1	1/621 (0.16%)	0/624 (0.00%)	1/619 (0.16%)
Cholecystitis ^† 1	0/621 (0.00%)	2/624 (0.32%)	3/619 (0.48%)
Pancreatitis ^† 1	1/621 (0.16%)	0/624 (0.00%)	0/619 (0.00%)
Immune system disorders
Allergy/Immunology - Other ^† 1	0/621 (0.00%)	0/624 (0.00%)	1/619 (0.16%)
Allergic Reaction/Hypersensitivity ^† 1	3/621 (0.48%)	6/624 (0.96%)	4/619 (0.65%)
Infections and infestations
Inf W/Gr 3 Or 4 Anc: Wound ^† 1	1/621 (0.16%)	0/624 (0.00%)	1/619 (0.16%)
Inf W/Gr 3 Or 4 Anc: Blood ^† 1	3/621 (0.48%)	1/624 (0.16%)	1/619 (0.16%)
Inf W/Gr 3 Or 4 Anc: Salivary Gland ^† 1	0/621 (0.00%)	0/624 (0.00%)	1/619 (0.16%)
Inf W/Gr 3 Or 4 Anc: Skin (Cellulitis) ^† 1	1/621 (0.16%)	0/624 (0.00%)	1/619 (0.16%)
Inf W/Gr 3 Or 4 Anc: External Ear ^† 1	0/621 (0.00%)	1/624 (0.16%)	0/619 (0.00%)
Inf W/Nml Or Gr 1 Or 2 Anc: Lung(Pneumonia) ^† 1	2/621 (0.32%)	3/624 (0.48%)	3/619 (0.48%)
Inf W/Gr 3 Or 4 Anc: Peritoneal Cavity ^† 1	0/621 (0.00%)	1/624 (0.16%)	0/619 (0.00%)
Inf W/Gr 3 Or 4 Anc: Esophagus ^† 1	0/621 (0.00%)	0/624 (0.00%)	1/619 (0.16%)
Inf W/Nml Or Gr 1 Or 2 Anc: Bone ^† 1	0/621 (0.00%)	1/624 (0.16%)	0/619 (0.00%)
Inf W/Nml Or Gr 1 Or 2 Anc: Blood ^† 1	3/621 (0.48%)	3/624 (0.48%)	1/619 (0.16%)
Inf W/Nml Or Gr 1 Or 2 Anc: Wound ^† 1	1/621 (0.16%)	2/624 (0.32%)	1/619 (0.16%)
Inf W/Nml Or Gr 1 Or 2 Anc: Skin(Cellulitis) ^† 1	2/621 (0.32%)	0/624 (0.00%)	2/619 (0.32%)
Inf W/Nml Or Gr 1 Or 2 Anc: Catheter-Related ^† 1	1/621 (0.16%)	2/624 (0.32%)	2/619 (0.32%)
Febrile Neutropenia ^† 1	16/621 (2.58%)	20/624 (3.21%)	21/619 (3.39%)
Inf W/Nml Or Gr 1 Or 2 Anc: Rectum ^† 1	0/621 (0.00%)	1/624 (0.16%)	0/619 (0.00%)
Inf Unknown Anc: Lung (Pneumonia) ^† 1	1/621 (0.16%)	0/624 (0.00%)	0/619 (0.00%)
Inf W/Nml Or Gr 1 Or 2 Anc: Urinary Tract Nos ^† 1	0/621 (0.00%)	1/624 (0.16%)	2/619 (0.32%)
Inf W/Nml Or Gr 1 Or 2 Anc: Abdomen Nos ^† 1	1/621 (0.16%)	3/624 (0.48%)	4/619 (0.65%)
Infection - Other ^† 1	4/621 (0.64%)	4/624 (0.64%)	3/619 (0.48%)
Inf W/Gr 3 Or 4 Anc: Bladder (Urinary) ^† 1	0/621 (0.00%)	2/624 (0.32%)	3/619 (0.48%)
Opportunisitic Inf Assoc. W/Gr 2 Lymphopenia ^† 1	1/621 (0.16%)	0/624 (0.00%)	0/619 (0.00%)
Colitis, Infectious (Eg.C. Difficile) ^† 1	1/621 (0.16%)	3/624 (0.48%)	0/619 (0.00%)
Inf W/Nml Or Gr 1 Or 2 Anc: Bronchus ^† 1	1/621 (0.16%)	0/624 (0.00%)	0/619 (0.00%)
Inf W/Gr 3 Or 4 Anc: Abdomen Nos ^† 1	3/621 (0.48%)	0/624 (0.00%)	0/619 (0.00%)
Inf W/Nml Or Gr 1 Or 2 Anc: Sinus ^† 1	1/621 (0.16%)	0/624 (0.00%)	0/619 (0.00%)
Inf W/Nml Or Gr 1 Or 2 Anc: Pelvis Nos ^† 1	0/621 (0.00%)	1/624 (0.16%)	0/619 (0.00%)
Inf Unknown Anc: Neck Nos ^† 1	0/621 (0.00%)	1/624 (0.16%)	0/619 (0.00%)
Inf W/Nml Or Gr 1 Or 2 Anc:peritoneal Cavity ^† 1	1/621 (0.16%)	0/624 (0.00%)	1/619 (0.16%)
Inf Unknown Anc: Catheter-Related ^† 1	0/621 (0.00%)	2/624 (0.32%)	0/619 (0.00%)
Inf W/Gr 3 Or 4 Anc: Pelvis Nos ^† 1	0/621 (0.00%)	2/624 (0.32%)	0/619 (0.00%)
Inf W/Gr 3 Or 4 Anc: Upper Airway Nos ^† 1	0/621 (0.00%)	0/624 (0.00%)	1/619 (0.16%)
Inf W/Gr 3 Or 4 Anc: Sinus ^† 1	1/621 (0.16%)	0/624 (0.00%)	0/619 (0.00%)
Inf W/Gr 3 Or 4 Anc: Lung (Pneumonia) ^† 1	3/621 (0.48%)	2/624 (0.32%)	1/619 (0.16%)
Inf W/Gr 3 Or 4 Anc: Urinary Tract Nos ^† 1	3/621 (0.48%)	4/624 (0.64%)	3/619 (0.48%)
Inf W/Gr 3 Or 4 Anc: Catheter-Related ^† 1	2/621 (0.32%)	0/624 (0.00%)	1/619 (0.16%)
Metabolism and nutrition disorders
Proteinuria ^† 1	0/621 (0.00%)	0/624 (0.00%)	1/619 (0.16%)
Creatinine ^† 1	0/621 (0.00%)	0/624 (0.00%)	1/619 (0.16%)
Hypoalbuminemia ^† 1	0/621 (0.00%)	0/624 (0.00%)	1/619 (0.16%)
Alt ^† 1	0/621 (0.00%)	1/624 (0.16%)	0/619 (0.00%)
Hyponatremia ^† 1	1/621 (0.16%)	1/624 (0.16%)	3/619 (0.48%)
Hyperglycemia ^† 1	0/621 (0.00%)	2/624 (0.32%)	2/619 (0.32%)
Hypokalemia ^† 1	3/621 (0.48%)	0/624 (0.00%)	2/619 (0.32%)
Hypoglycemia ^† 1	1/621 (0.16%)	0/624 (0.00%)	0/619 (0.00%)
Hypercalcemia ^† 1	0/621 (0.00%)	0/624 (0.00%)	1/619 (0.16%)
Hypomagnesemia ^† 1	0/621 (0.00%)	0/624 (0.00%)	1/619 (0.16%)
Musculoskeletal and connective tissue disorders
Musculoskeletal/St: Other ^† 1	0/621 (0.00%)	1/624 (0.16%)	0/619 (0.00%)
Soft Tissue Necrosis - Abdomen ^† 1	1/621 (0.16%)	0/624 (0.00%)	0/619 (0.00%)
Joint-Function ^† 1	0/621 (0.00%)	0/624 (0.00%)	1/619 (0.16%)
Joint Effusion ^† 1	0/621 (0.00%)	1/624 (0.16%)	0/619 (0.00%)
Fracture ^† 1	2/621 (0.32%)	0/624 (0.00%)	3/619 (0.48%)
Osteonecrosis ^† 1	1/621 (0.16%)	0/624 (0.00%)	0/619 (0.00%)
Arthritis ^† 1	0/621 (0.00%)	0/624 (0.00%)	1/619 (0.16%)
Muscle Weakness - Whole Body/Generalized ^† 1	0/621 (0.00%)	0/624 (0.00%)	2/619 (0.32%)
Muscle Weakness - Extremity-Lower ^† 1	0/621 (0.00%)	0/624 (0.00%)	1/619 (0.16%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
2nd Mal: Poss. Related To Cancer Rx ^† 1	1/621 (0.16%)	0/624 (0.00%)	0/619 (0.00%)
Nervous system disorders
Syncope ^† 1	5/621 (0.81%)	4/624 (0.64%)	2/619 (0.32%)
Psychosis ^† 1	1/621 (0.16%)	1/624 (0.16%)	0/619 (0.00%)
Neurology - Other ^† 1	1/621 (0.16%)	0/624 (0.00%)	2/619 (0.32%)
Encephalopathy ^† 1	0/621 (0.00%)	1/624 (0.16%)	1/619 (0.16%)
Mood Alteration - Depression ^† 1	1/621 (0.16%)	0/624 (0.00%)	1/619 (0.16%)
Mood Alteration - Anxiety ^† 1	0/621 (0.00%)	1/624 (0.16%)	1/619 (0.16%)
Seizure ^† 1	1/621 (0.16%)	0/624 (0.00%)	1/619 (0.16%)
Cognitive Disturbance ^† 1	0/621 (0.00%)	2/624 (0.32%)	0/619 (0.00%)
Cns Ischemia ^† 1	3/621 (0.48%)	0/624 (0.00%)	5/619 (0.81%)
Confusion ^† 1	1/621 (0.16%)	1/624 (0.16%)	1/619 (0.16%)
Dizziness ^† 1	2/621 (0.32%)	1/624 (0.16%)	2/619 (0.32%)
Neuropathy-Sensory ^† 1	2/621 (0.32%)	0/624 (0.00%)	0/619 (0.00%)
Neuropathy-Motor ^† 1	0/621 (0.00%)	2/624 (0.32%)	1/619 (0.16%)
Renal and urinary disorders
Perforation, Gu - Vagina ^† 1	1/621 (0.16%)	0/624 (0.00%)	0/619 (0.00%)
Obstruction, Gu - Ureter ^† 1	0/621 (0.00%)	1/624 (0.16%)	0/619 (0.00%)
Fistula, Gu - Vagina ^† 1	1/621 (0.16%)	0/624 (0.00%)	0/619 (0.00%)
Respiratory, thoracic and mediastinal disorders
Pulmonary: Other ^† 1	3/621 (0.48%)	2/624 (0.32%)	2/619 (0.32%)
Bronchospasm ^† 1	0/621 (0.00%)	1/624 (0.16%)	0/619 (0.00%)
Pneumothorax ^† 1	2/621 (0.32%)	0/624 (0.00%)	1/619 (0.16%)
Pneumonitis ^† 1	1/621 (0.16%)	1/624 (0.16%)	1/619 (0.16%)
Pleural Effusion ^† 1	1/621 (0.16%)	3/624 (0.48%)	1/619 (0.16%)
Dyspnea ^† 1	3/621 (0.48%)	6/624 (0.96%)	7/619 (1.13%)
Skin and subcutaneous tissue disorders
Wound Complication, Non-Infectious ^† 1	3/621 (0.48%)	4/624 (0.64%)	4/619 (0.65%)
Pruritus ^† 1	0/621 (0.00%)	1/624 (0.16%)	0/619 (0.00%)
Dermatology/Skin - Other ^† 1	1/621 (0.16%)	1/624 (0.16%)	0/619 (0.00%)
Ulceration ^† 1	0/621 (0.00%)	1/624 (0.16%)	1/619 (0.16%)
Vascular disorders
Inr ^† 1	0/621 (0.00%)	0/624 (0.00%)	1/619 (0.16%)
Hemorrhage, Gu - Vagina ^† 1	0/621 (0.00%)	0/624 (0.00%)	1/619 (0.16%)
Hemorrhage, Gi - Rectum ^† 1	1/621 (0.16%)	0/624 (0.00%)	0/619 (0.00%)
Hemorrhage, Gi - Upper Gi Nos ^† 1	0/621 (0.00%)	1/624 (0.16%)	0/619 (0.00%)
Hemorrhage/Pulmonary - Nose ^† 1	0/621 (0.00%)	0/624 (0.00%)	1/619 (0.16%)
Hematoma ^† 1	1/621 (0.16%)	0/624 (0.00%)	0/619 (0.00%)
Hemorrhage, Gi - Lower Gi Nos ^† 1	0/621 (0.00%)	0/624 (0.00%)	2/619 (0.32%)
Hemorrhage, Gu - Kidney ^† 1	0/621 (0.00%)	0/624 (0.00%)	1/619 (0.16%)
Hemorrhage, Gi - Stomach ^† 1	0/621 (0.00%)	1/624 (0.16%)	1/619 (0.16%)
Hemorrhage, Cns ^† 1	0/621 (0.00%)	0/624 (0.00%)	1/619 (0.16%)
Hemorrhage/Bleeding - Other ^† 1	0/621 (0.00%)	0/624 (0.00%)	1/619 (0.16%)
Artery Injury - Carotid ^† 1	0/621 (0.00%)	1/624 (0.16%)	0/619 (0.00%)
Thrombosis/Embolism (Vascular Access-Related) ^† 1	2/621 (0.32%)	5/624 (0.80%)	2/619 (0.32%)
Thrombosis/Thrombus/Embolism ^† 1	17/621 (2.74%)	14/624 (2.24%)	21/619 (3.39%)
† Indicates events were collected by systematic assessment 1 Term from vocabulary, CTCAE (3.0)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Arm I (Placebo, Paclitaxel, Carboplatin)	Arm II (Placebo, Paclitaxel, Carboplatin, Bevacizumab)	Arm III (Paclitaxel, Carboplatin, Bevacizumab)
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	589/621 (94.85%)	593/624 (95.03%)	588/619 (94.99%)
Blood and lymphatic system disorders
Neutrophils ^† 1	589/621 (94.85%)	591/624 (94.71%)	588/619 (94.99%)
Platelets ^† 1	419/621 (67.47%)	426/624 (68.27%)	435/619 (70.27%)
Leukocytes ^† 1	578/621 (93.08%)	593/624 (95.03%)	586/619 (94.67%)
Lymphopenia ^† 1	33/621 (5.31%)	27/624 (4.33%)	32/619 (5.17%)
Hemoglobin ^† 1	587/621 (94.52%)	574/624 (91.99%)	572/619 (92.41%)
Edema: Limb ^† 1	115/621 (18.52%)	82/624 (13.14%)	89/619 (14.38%)
Cardiac disorders
Palpitations ^† 1	31/621 (4.99%)	22/624 (3.53%)	30/619 (4.85%)
Hypertension ^† 1	90/621 (14.49%)	149/624 (23.88%)	206/619 (33.28%)
Hypotension ^† 1	25/621 (4.03%)	25/624 (4.01%)	33/619 (5.33%)
Ear and labyrinth disorders
Tinnitus ^† 1	28/621 (4.51%)	18/624 (2.88%)	32/619 (5.17%)
Endocrine disorders
Hot Flashes ^† 1	100/621 (16.10%)	70/624 (11.22%)	97/619 (15.67%)
Eye disorders
Blurred Vision ^† 1	72/621 (11.59%)	72/624 (11.54%)	94/619 (15.19%)
Gastrointestinal disorders
Heartburn ^† 1	71/621 (11.43%)	76/624 (12.18%)	90/619 (14.54%)
Distention ^† 1	53/621 (8.53%)	38/624 (6.09%)	36/619 (5.82%)
Taste Alteration ^† 1	75/621 (12.08%)	70/624 (11.22%)	75/619 (12.12%)
Mucositis (Functional/Sympt) - Oral Cavity ^† 1	58/621 (9.34%)	65/624 (10.42%)	103/619 (16.64%)
Mucositis (Clinical Exam) - Oral Cavity ^† 1	57/621 (9.18%)	86/624 (13.78%)	97/619 (15.67%)
Vomiting ^† 1	221/621 (35.59%)	216/624 (34.62%)	236/619 (38.13%)
Anorexia ^† 1	184/621 (29.63%)	202/624 (32.37%)	202/619 (32.63%)
Dehydration ^† 1	38/621 (6.12%)	62/624 (9.94%)	52/619 (8.40%)
Constipation ^† 1	377/621 (60.71%)	351/624 (56.25%)	355/619 (57.35%)
Nausea ^† 1	388/621 (62.48%)	399/624 (63.94%)	403/619 (65.11%)
Diarrhea ^† 1	240/621 (38.65%)	265/624 (42.47%)	260/619 (42.00%)
General disorders
Sweating ^† 1	36/621 (5.80%)	37/624 (5.93%)	31/619 (5.01%)
Weight Gain ^† 1	117/621 (18.84%)	106/624 (16.99%)	103/619 (16.64%)
Fever ^† 1	61/621 (9.82%)	48/624 (7.69%)	74/619 (11.95%)
Weight Loss ^† 1	76/621 (12.24%)	80/624 (12.82%)	101/619 (16.32%)
Rigors/Chills ^† 1	36/621 (5.80%)	35/624 (5.61%)	43/619 (6.95%)
Fatigue ^† 1	515/621 (82.93%)	517/624 (82.85%)	532/619 (85.95%)
Insomnia ^† 1	125/621 (20.13%)	136/624 (21.79%)	134/619 (21.65%)
Pain - Other ^† 1	40/621 (6.44%)	41/624 (6.57%)	43/619 (6.95%)
Pain: Chest /Thorax Nos ^† 1	32/621 (5.15%)	34/624 (5.45%)	30/619 (4.85%)
Pain: Head/Headache ^† 1	128/621 (20.61%)	142/624 (22.76%)	193/619 (31.18%)
Pain: Extremity-Limb ^† 1	93/621 (14.98%)	101/624 (16.19%)	142/619 (22.94%)
Pain: Back ^† 1	99/621 (15.94%)	109/624 (17.47%)	127/619 (20.52%)
Pain: Joint ^† 1	214/621 (34.46%)	199/624 (31.89%)	245/619 (39.58%)
Pain: Bone ^† 1	61/621 (9.82%)	52/624 (8.33%)	58/619 (9.37%)
Pain: Abdominal Pain Nos ^† 1	257/621 (41.38%)	247/624 (39.58%)	249/619 (40.23%)
Pain: Muscle ^† 1	152/621 (24.48%)	155/624 (24.84%)	169/619 (27.30%)
Immune system disorders
Allergic Reaction/Hypersensitivity ^† 1	56/621 (9.02%)	65/624 (10.42%)	68/619 (10.99%)
Rhinitis ^† 1	67/621 (10.79%)	93/624 (14.90%)	98/619 (15.83%)
Infections and infestations
Inf W/Nml Or Gr 1 Or 2 Anc: Urinary Tract Nos ^† 1	38/621 (6.12%)	40/624 (6.41%)	42/619 (6.79%)
Metabolism and nutrition disorders
Ast ^† 1	75/621 (12.08%)	63/624 (10.10%)	86/619 (13.89%)
Proteinuria ^† 1	40/621 (6.44%)	33/624 (5.29%)	59/619 (9.53%)
Creatinine ^† 1	36/621 (5.80%)	36/624 (5.77%)	53/619 (8.56%)
Hypoalbuminemia ^† 1	62/621 (9.98%)	71/624 (11.38%)	79/619 (12.76%)
Alt ^† 1	78/621 (12.56%)	66/624 (10.58%)	76/619 (12.28%)
Alkaline Phosphatase ^† 1	74/621 (11.92%)	64/624 (10.26%)	83/619 (13.41%)
Hyponatremia ^† 1	77/621 (12.40%)	75/624 (12.02%)	98/619 (15.83%)
Hypocalcemia ^† 1	62/621 (9.98%)	58/624 (9.29%)	65/619 (10.50%)
Hyperkalemia ^† 1	35/621 (5.64%)	32/624 (5.13%)	42/619 (6.79%)
Hyperglycemia ^† 1	162/621 (26.09%)	152/624 (24.36%)	159/619 (25.69%)
Hypokalemia ^† 1	103/621 (16.59%)	94/624 (15.06%)	87/619 (14.05%)
Hypoglycemia ^† 1	29/621 (4.67%)	31/624 (4.97%)	42/619 (6.79%)
Hypercalcemia ^† 1	28/621 (4.51%)	33/624 (5.29%)	29/619 (4.68%)
Hypomagnesemia ^† 1	95/621 (15.30%)	104/624 (16.67%)	104/619 (16.80%)
Musculoskeletal and connective tissue disorders
Muscle Weakness - Whole Body/Generalized ^† 1	45/621 (7.25%)	55/624 (8.81%)	59/619 (9.53%)
Muscle Weakness - Extremity-Lower ^† 1	26/621 (4.19%)	31/624 (4.97%)	42/619 (6.79%)
Nervous system disorders
Mood Alteration - Depression ^† 1	80/621 (12.88%)	90/624 (14.42%)	101/619 (16.32%)
Mood Alteration - Anxiety ^† 1	99/621 (15.94%)	92/624 (14.74%)	96/619 (15.51%)
Memory Impairment ^† 1	27/621 (4.35%)	32/624 (5.13%)	29/619 (4.68%)
Dizziness ^† 1	104/621 (16.75%)	108/624 (17.31%)	140/619 (22.62%)
Neuropathy-Sensory ^† 1	435/621 (70.05%)	432/624 (69.23%)	434/619 (70.11%)
Neuropathy-Motor ^† 1	57/621 (9.18%)	39/624 (6.25%)	48/619 (7.75%)
Renal and urinary disorders
Incontinence, Urinary ^† 1	35/621 (5.64%)	36/624 (5.77%)	22/619 (3.55%)
Urinary Frequency ^† 1	39/621 (6.28%)	46/624 (7.37%)	48/619 (7.75%)
Respiratory, thoracic and mediastinal disorders
Nasal/Paranasal Reactions ^† 1	26/621 (4.19%)	46/624 (7.37%)	65/619 (10.50%)
Voice Changes ^† 1	10/621 (1.61%)	58/624 (9.29%)	73/619 (11.79%)
Cough ^† 1	112/621 (18.04%)	115/624 (18.43%)	143/619 (23.10%)
Dyspnea ^† 1	151/621 (24.32%)	180/624 (28.85%)	179/619 (28.92%)
Skin and subcutaneous tissue disorders
Nail Changes ^† 1	20/621 (3.22%)	29/624 (4.65%)	42/619 (6.79%)
Hair Loss/Alopecia (Scalp Or Body) ^† 1	452/621 (72.79%)	459/624 (73.56%)	444/619 (71.73%)
Bruising ^† 1	31/621 (4.99%)	31/624 (4.97%)	36/619 (5.82%)
Rash ^† 1	127/621 (20.45%)	123/624 (19.71%)	148/619 (23.91%)
Dry Skin ^† 1	35/621 (5.64%)	33/624 (5.29%)	36/619 (5.82%)
Pruritus ^† 1	57/621 (9.18%)	59/624 (9.46%)	66/619 (10.66%)
Flushing ^† 1	35/621 (5.64%)	33/624 (5.29%)	31/619 (5.01%)
Dermatology/Skin - Other ^† 1	37/621 (5.96%)	27/624 (4.33%)	33/619 (5.33%)
Vascular disorders
Hemorrhage/Pulmonary - Nose ^† 1	60/621 (9.66%)	181/624 (29.01%)	188/619 (30.37%)
† Indicates events were collected by systematic assessment 1 Term from vocabulary, CTCAE (3.0)

Limitations and Caveats

The results for both Overall Survival (OS) and Progression Free Survival (PFS) were based on the analysis performed on a data set frozen on August 26, 2011.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Melissa Leventhal
Organization:	Gynecologic Oncology Group (GOG) Statistical and Data Center
Phone:	716-845-4030
EMail:	mleventhal@gogstats.org

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

You B, Purdy C, Copeland LJ, Swisher EM, Bookman MA, Fleming G, Coleman R, Randall LM, Tewari KS, Monk BJ, Mannel RS, Walker JL, Cappuccini F, Cohn D, Muzaffar M, Mutch D, Wahner-Hendrickson A, Martin L, Colomban O, Burger RA. Identification of Patients With Ovarian Cancer Experiencing the Highest Benefit From Bevacizumab in the First-Line Setting on the Basis of Their Tumor-Intrinsic Chemosensitivity (KELIM): The GOG-0218 Validation Study. J Clin Oncol. 2022 Dec 1;40(34):3965-3974. doi: 10.1200/JCO.22.01207. Epub 2022 Oct 17.

Morgan RD, Ferreras C, Peset I, Avizienyte E, Renehan AG, Edmondson RJ, Murphy AD, Nicum S, Van Brussel T, Clamp AR, Lambrechts D, Zhou C, Jayson GC. c-MET/VEGFR-2 co-localisation impacts on survival following bevacizumab therapy in epithelial ovarian cancer: an exploratory biomarker study of the phase 3 ICON7 trial. BMC Med. 2022 Feb 11;20(1):59. doi: 10.1186/s12916-022-02270-y.

Tewari KS, Burger RA, Enserro D, Norquist BM, Swisher EM, Brady MF, Bookman MA, Fleming GF, Huang H, Homesley HD, Fowler JM, Greer BE, Boente M, Liang SX, Ye C, Bais C, Randall LM, Chan JK, Ferriss JS, Coleman RL, Aghajanian C, Herzog TJ, DiSaia PJ, Copeland LJ, Mannel RS, Birrer MJ, Monk BJ. Final Overall Survival of a Randomized Trial of Bevacizumab for Primary Treatment of Ovarian Cancer. J Clin Oncol. 2019 Sep 10;37(26):2317-2328. doi: 10.1200/JCO.19.01009. Epub 2019 Jun 19.

Eskander RN, Kauderer J, Tewari KS, Mannel RS, Bristow RE, O'Malley DM, Rubin SC, Glaser GE, Hamilton CA, Fujiwara K, Huh WK, Ueland F, Stephan JM, Burger RA. Correlation between Surgeon's assessment and radiographic evaluation of residual disease in women with advanced stage ovarian cancer reported to have undergone optimal surgical cytoreduction: An NRG Oncology/Gynecologic Oncology Group study. Gynecol Oncol. 2018 Jun;149(3):525-530. doi: 10.1016/j.ygyno.2018.03.043. Epub 2018 Mar 15.

Tewari KS, Java JJ, Eskander RN, Monk BJ, Burger RA. Early initiation of chemotherapy following complete resection of advanced ovarian cancer associated with improved survival: NRG Oncology/Gynecologic Oncology Group study. Ann Oncol. 2016 Jan;27(1):114-21. doi: 10.1093/annonc/mdv500. Epub 2015 Oct 20.

Monk BJ, Huang HQ, Burger RA, Mannel RS, Homesley HD, Fowler J, Greer BE, Boente M, Liang SX, Wenzel L. Patient reported outcomes of a randomized, placebo-controlled trial of bevacizumab in the front-line treatment of ovarian cancer: a Gynecologic Oncology Group Study. Gynecol Oncol. 2013 Mar;128(3):573-8. doi: 10.1016/j.ygyno.2012.11.038. Epub 2012 Dec 4.

Burger RA, Brady MF, Bookman MA, Fleming GF, Monk BJ, Huang H, Mannel RS, Homesley HD, Fowler J, Greer BE, Boente M, Birrer MJ, Liang SX; Gynecologic Oncology Group. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med. 2011 Dec 29;365(26):2473-83. doi: 10.1056/NEJMoa1104390.

Vaughan S, Coward JI, Bast RC Jr, Berchuck A, Berek JS, Brenton JD, Coukos G, Crum CC, Drapkin R, Etemadmoghadam D, Friedlander M, Gabra H, Kaye SB, Lord CJ, Lengyel E, Levine DA, McNeish IA, Menon U, Mills GB, Nephew KP, Oza AM, Sood AK, Stronach EA, Walczak H, Bowtell DD, Balkwill FR. Rethinking ovarian cancer: recommendations for improving outcomes. Nat Rev Cancer. 2011 Sep 23;11(10):719-25. doi: 10.1038/nrc3144.

Layout table for additonal information

Responsible Party:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00262847
Other Study ID Numbers:	NCI-2009-00590 NCI-2009-00590 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) CDR0000455114 GOG-0218 ( Other Identifier: NRG Oncology ) GOG-0218 ( Other Identifier: CTEP ) U10CA180868 ( U.S. NIH Grant/Contract ) U10CA027469 ( U.S. NIH Grant/Contract )
First Submitted:	December 6, 2005
First Posted:	December 7, 2005
Results First Submitted:	July 9, 2013
Results First Posted:	September 18, 2013
Last Update Posted:	July 23, 2019

To Top