A Study of Carboplatin and Gemcitabine Plus Bevacizumab in Patients With Ovary, Peritoneal, or Fallopian Tube Carcinoma (OCEANS)

• ClinicalTrials.gov Identifier: NCT00434642
• Recruitment Status: Completed
• First Posted: February 13, 2007
• Results First Posted: November 3, 2011
• Last Update Posted: August 9, 2017
• Sponsor: Genentech, Inc.
• Information provided by (Responsible Party): Genentech, Inc.

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Ovarian Cancer
• Interventions: Drug: Carboplatin; Drug: Gemcitabine; Drug: Bevacizumab; Drug: Placebo
• Enrollment: 484

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Carboplatin and Gemcitabine + Placebo	Carboplatin and Gemcitabine + Bevacizumab
Arm/Group Description	Carboplatin (AUC 4 mg/mL/minute) was administered intravenously (IV) on Day 1 of each of six 21-day treatment cycles. The carboplatin dose was calculated to reach a target area under the curve (AUC) of concentration x time according to the Calvert formula. Gemcitabine 1000 mg/m^2 was administered IV on Days 1 and Day 8 of each of the six 21-day treatment cycles. Placebo was administered by IV on Day 1 of each of the six 21-day treatment cycles.	Carboplatin (AUC 4 mg/mL/minute) was administered intravenously (IV) on Day 1 of each of six 21-day treatment cycles. The carboplatin dose was calculated to reach a target area under the curve (AUC) of concentration x time according to the Calvert formula. Gemcitabine 1000 mg/m^2 was administered IV on Days 1 and Day 8 of each of the six 21-day treatment cycles. Bevacizumab 15 mg/kg was administered IV on Day 1 of each of the six 21-day treatment cycles. The bevacizumab dose was based on the patient's weight at baseline and remained the same throughout the study.
Period Title: Blinded Treatment Phase
Started	242	242
Completed	0	13
Not Completed	242	229
Reason Not Completed
Adverse Event	12	58
Clinical Disease Progression	4	5
Disease Progression Per RECIST	168	109
Physician Decision	19	27
Sponsor's Decision To Terminate Study	3	0
Subject's Decision-Discontinue Treatment	32	29
Did not Receive Treatment	4	1
Period Title: Open-label Treatment Phase
Started	0	12 [1]
Completed	0	1
Not Completed	0	11
Reason Not Completed
Adverse Event	0	5
Disease Progression Per RECIST	0	6
[1] One participant did not continue into the open-label treatment phase.

Baseline Characteristics

Arm/Group Title		Carboplatin and Gemcitabine + Placebo	Carboplatin and Gemcitabine + Bevacizumab	Total
Arm/Group Description		Carboplatin (AUC 4 mg/mL/minute) was administered intravenously (IV) on Day 1 of each of six 21-day treatment cycles. The carboplatin dose was calculated to reach a target area under the curve (AUC) of concentration x time according to the Calvert formula. Gemcitabine 1000 mg/m^2 was administered IV on Days 1 and Day 8 of each of the six 21-day treatment cycles. Placebo was administered by IV on Day 1 of each of the six 21-day treatment cycles.	Carboplatin (AUC 4 mg/mL/minute) was administered intravenously (IV) on Day 1 of each of six 21-day treatment cycles. The carboplatin dose was calculated to reach a target area under the curve (AUC) of concentration x time according to the Calvert formula. Gemcitabine 1000 mg/m^2 was administered IV on Days 1 and Day 8 of each of the six 21-day treatment cycles. Bevacizumab 15 mg/kg was administered IV on Day 1 of each of the six 21-day treatment cycles. The bevacizumab dose was based on the patient's weight at baseline and remained the same throughout the study.	Total of all reporting groups
Overall Number of Baseline Participants		242	242	484
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	242 participants	242 participants	484 participants
		61.6 (10.2)	60.5 (9.8)	61.0 (10.0)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	242 participants	242 participants	484 participants
	Female	242 100.0%	242 100.0%	484 100.0%
	Male	0 0.0%	0 0.0%	0 0.0%

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival (PFS) as Determined by the Investigator, Per Response Evaluation Criteria for Solid Tumors (RECIST)
Description	PFS was defined as the time from randomization to disease progression (PD), as determined by the investigator, or death due to any cause. PD: 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; the appearance of 1 or more new lesions; and/or the unequivocal progression of existing non-target lesions. Lesions were assessed by computed tomography (CT), magnetic resonance imaging (MRI), or ultrasound every 9 weeks.
Time Frame	From randomization through September 17, 2010 (up to 3 years, 5 months)

Outcome Measure Data

Analysis Population Description

Intent-to-treat population: All patients randomized to treatment (242 patients in each treatment group).

Arm/Group Title	Carboplatin and Gemcitabine + Bevacizumab	Carboplatin and Gemcitabine + Placebo
Arm/Group Description:	Carboplatin (AUC 4 mg/mL/minute) was administered intravenously (IV) on Day 1 of each of six 21-day treatment cycles. The carboplatin dose was calculated to reach a target area under the curve (AUC) of concentration x time according to the Calvert formula. Gemcitabine 1000 mg/m^2 was administered IV on Days 1 and Day 8 of each of the six 21-day treatment cycles. Bevacizumab 15 mg/kg was administered IV on Day 1 of each of the six 21-day treatment cycles. The bevacizumab dose was based on the patient's weight at baseline and remained the same throughout the study.	Carboplatin (AUC 4 mg/mL/minute) was administered intravenously (IV) on Day 1 of each of six 21-day treatment cycles. The carboplatin dose was calculated to reach a target area under the curve (AUC) of concentration x time according to the Calvert formula. Gemcitabine 1000 mg/m^2 was administered IV on Days 1 and Day 8 of each of the six 21-day treatment cycles. Placebo was administered by IV on Day 1 of each of the six 21-day treatment cycles.
Overall Number of Participants Analyzed	242	242
Median (95% Confidence Interval); Unit of Measure: Months
	12.4; (11.40 to 12.71)	8.4; (8.31 to 9.66)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Carboplatin and Gemcitabine + Bevacizumab, Carboplatin and Gemcitabine + Placebo
	Comments	The null hypothesis was that there was no difference between the 2 treatment groups, ie, that the hazard ratio is equal to 1. The alternative hypothesis was that progression free survival was longer in the carboplatin and gemcitabine + bevacizumab group, ie, that the hazard ratio is not equal to 1.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	A P-value < 0.05 was required for significance.
	Method	Log Rank
	Comments	The analysis was stratified for time since the last platinum therapy (6-12, > 12 months) and cytoreductive surgery for recurrent disease (yes, no).
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.484
	Confidence Interval	(2-Sided) 95%; 0.388 to 0.605
	Estimation Comments	The hazard ratio was estimated using Cox regression. The hazard ratio is relative to the carboplatin and gemcitabine + placebo group.

2. Secondary Outcome

Title	Percentage of Patients With an Objective Response as Determined by the Investigator, Per Response Evaluation Criteria for Solid Tumors (RECIST)
Description	An objective response was the occurrence of either a partial response (PR) or complete response (CR). PR: At least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter. CR: The disappearance of all target and non-target lesions. Lesions were assessed by computed tomography (CT), magnetic resonance imaging (MRI), or ultrasound every 9 weeks.
Time Frame	From randomization through September 17, 2010 (up to 3 years, 5 months)

Outcome Measure Data

Analysis Population Description

Intent-to-treat population: All patients randomized to treatment (242 patients in each treatment group).

Arm/Group Title	Carboplatin and Gemcitabine + Bevacizumab	Carboplatin and Gemcitabine + Placebo
Arm/Group Description:	Carboplatin (AUC 4 mg/mL/minute) was administered intravenously (IV) on Day 1 of each of six 21-day treatment cycles. The carboplatin dose was calculated to reach a target area under the curve (AUC) of concentration x time according to the Calvert formula. Gemcitabine 1000 mg/m^2 was administered IV on Days 1 and Day 8 of each of the six 21-day treatment cycles. Bevacizumab 15 mg/kg was administered IV on Day 1 of each of the six 21-day treatment cycles. The bevacizumab dose was based on the patient's weight at baseline and remained the same throughout the study.	Carboplatin (AUC 4 mg/mL/minute) was administered intravenously (IV) on Day 1 of each of six 21-day treatment cycles. The carboplatin dose was calculated to reach a target area under the curve (AUC) of concentration x time according to the Calvert formula. Gemcitabine 1000 mg/m^2 was administered IV on Days 1 and Day 8 of each of the six 21-day treatment cycles. Placebo was administered by IV on Day 1 of each of the six 21-day treatment cycles.
Overall Number of Participants Analyzed	242	242
Measure Type: Number; Unit of Measure: Percentage of participants
	78.5	57.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Carboplatin and Gemcitabine + Bevacizumab, Carboplatin and Gemcitabine + Placebo
	Comments	The null hypothesis was that there was no difference in the percentage of patients with an objective response between the 2 treatment groups. The alternative hypothesis was that a larger percentage of patients had an objective response in the carboplatin and gemcitabine + bevacizumab group.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	A P-value < 0.05 was required for significance.
	Method	Cochran-Mantel-Haenszel
	Comments	The analysis was stratified for time since the last platinum therapy (6-12, > 12 months) and cytoreductive surgery for recurrent disease (yes, no).
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	21.1
	Confidence Interval	(2-Sided) 95%; 13.0 to 29.2
	Estimation Comments	The difference in response rates and the 95% confidence intervals for response rates were computed using the normal approximation to the binomial distribution.

3. Secondary Outcome

Title	Duration of Objective Response (OR) as Determined by the Investigator, Per Response Evaluation Criteria for Solid Tumors (RECIST)
Description	Duration of OR was analyzed in the subset of patients who achieved an OR. The duration of OR was defined as the time from the initial CR or PR until documented PD or death. Lesions were assessed by computed tomography (CT), magnetic resonance imaging (MRI), or ultrasound every 9 weeks.
Time Frame	From randomization through September 17, 2010 (up to 3 years, 5 months)

Outcome Measure Data

Analysis Population Description

Subset of the intent-to-treat population: All patients randomized to treatment who achieved an objective response.

Arm/Group Title	Carboplatin and Gemcitabine + Bevacizumab	Carboplatin and Gemcitabine + Placebo
Arm/Group Description:	Carboplatin (AUC 4 mg/mL/minute) was administered intravenously (IV) on Day 1 of each of six 21-day treatment cycles. The carboplatin dose was calculated to reach a target area under the curve (AUC) of concentration x time according to the Calvert formula. Gemcitabine 1000 mg/m^2 was administered IV on Days 1 and Day 8 of each of the six 21-day treatment cycles. Bevacizumab 15 mg/kg was administered IV on Day 1 of each of the six 21-day treatment cycles. The bevacizumab dose was based on the patient's weight at baseline and remained the same throughout the study.	Carboplatin (AUC 4 mg/mL/minute) was administered intravenously (IV) on Day 1 of each of six 21-day treatment cycles. The carboplatin dose was calculated to reach a target area under the curve (AUC) of concentration x time according to the Calvert formula. Gemcitabine 1000 mg/m^2 was administered IV on Days 1 and Day 8 of each of the six 21-day treatment cycles. Placebo was administered by IV on Day 1 of each of the six 21-day treatment cycles.
Overall Number of Participants Analyzed	190	139
Median (95% Confidence Interval); Unit of Measure: Months
	10.4; (9.36 to 11.83)	7.4; (6.31 to 8.31)

4. Secondary Outcome

Title	Overall Survival
Description	Overall survival was defined as the time from randomization to death from any cause.
Time Frame	From randomization through July 19, 2013 (up to 6 years, 3 months)

Outcome Measure Data

Analysis Population Description

Intent-to-treat population: All patients randomized to treatment (242 patients in each treatment group).

Arm/Group Title	Carboplatin and Gemcitabine + Bevacizumab	Carboplatin and Gemcitabine + Placebo
Arm/Group Description:	Carboplatin (AUC 4 mg/mL/minute) was administered intravenously (IV) on Day 1 of each of six 21-day treatment cycles. The carboplatin dose was calculated to reach a target area under the curve (AUC) of concentration x time according to the Calvert formula. Gemcitabine 1000 mg/m^2 was administered IV on Days 1 and Day 8 of each of the six 21-day treatment cycles. Bevacizumab 15 mg/kg was administered IV on Day 1 of each of the six 21-day treatment cycles. The bevacizumab dose was based on the patient's weight at baseline and remained the same throughout the study.	Carboplatin (AUC 4 mg/mL/minute) was administered intravenously (IV) on Day 1 of each of six 21-day treatment cycles. The carboplatin dose was calculated to reach a target area under the curve (AUC) of concentration x time according to the Calvert formula. Gemcitabine 1000 mg/m^2 was administered IV on Days 1 and Day 8 of each of the six 21-day treatment cycles. Placebo was administered by IV on Day 1 of each of the six 21-day treatment cycles.
Overall Number of Participants Analyzed	242	242
Median (95% Confidence Interval); Unit of Measure: Months
	33.6; (30.32 to 35.84)	32.9; (29.80 to 37.68)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Carboplatin and Gemcitabine + Bevacizumab, Carboplatin and Gemcitabine + Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.6479
	Comments	Summaries of duration of overall survival (median, percentiles) were estimated from Kaplan-Meier curves. The 95% confidence interval for the median was computed using the method of Brookmeyer and Crowley.
	Method	Log Rank
	Comments	The analysis was stratified for time since the last platinum therapy (≤12, >12 months) and cytoreductive surgery for recurrent disease (Yes, No).
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.952
	Confidence Interval	(2-Sided) 95%; 0.771 to 1.176
	Estimation Comments	The hazard ratio was estimated using Cox regression. The hazard ratio is relative to the carboplatin and gemcitabine + placebo group.

5. Secondary Outcome

Title	Percentage of Patients Who Had a Gastrointestinal Perforation (GIP)
Description	A gastrointestinal perforation is a hole that develops through the entire wall of the stomach, small intestine, large bowel, or gallbladder.
Time Frame	From randomization through September 17, 2010 (up to 3 years, 5 months)

Outcome Measure Data

Analysis Population Description

Safety population: All patients who received at least 1 dose of protocol treatment. Due to errors in drug administration, the safety population included 247 patients in the carboplatin and gemcitabine + bevacizumab group and 233 patients in the carboplatin and gemcitabine + placebo group.

Arm/Group Title	Carboplatin and Gemcitabine + Bevacizumab	Carboplatin and Gemcitabine + Placebo
Arm/Group Description:	Carboplatin (AUC 4 mg/mL/minute) was administered intravenously (IV) on Day 1 of each of six 21-day treatment cycles. The carboplatin dose was calculated to reach a target area under the curve (AUC) of concentration x time according to the Calvert formula. Gemcitabine 1000 mg/m^2 was administered IV on Days 1 and Day 8 of each of the six 21-day treatment cycles. Bevacizumab 15 mg/kg was administered IV on Day 1 of each of the six 21-day treatment cycles. The bevacizumab dose was based on the patient's weight at baseline and remained the same throughout the study.	Carboplatin (AUC 4 mg/mL/minute) was administered intravenously (IV) on Day 1 of each of six 21-day treatment cycles. The carboplatin dose was calculated to reach a target area under the curve (AUC) of concentration x time according to the Calvert formula. Gemcitabine 1000 mg/m^2 was administered IV on Days 1 and Day 8 of each of the six 21-day treatment cycles. Placebo was administered by IV on Day 1 of each of the six 21-day treatment cycles.
Overall Number of Participants Analyzed	247	233
Measure Type: Number; Unit of Measure: Percentage of participants
	0	0

6. Secondary Outcome

Title	Percentage of Patients Who Had at Least 1 Adverse Event
Description	[Not Specified]
Time Frame	From randomization through July 19, 2013 (up to 6 years, 3 months)

Outcome Measure Data

Analysis Population Description

Safety population: All patients who received at least 1 dose of protocol treatment. Due to errors in drug administration, the safety population included 247 patients in the carboplatin and gemcitabine + bevacizumab group and 233 patients in the carboplatin and gemcitabine + placebo group.

Arm/Group Title	Carboplatin and Gemcitabine + Bevacizumab	Carboplatin and Gemcitabine + Placebo
Arm/Group Description:	Carboplatin (AUC 4 mg/mL/minute) was administered intravenously (IV) on Day 1 of each of six 21-day treatment cycles. The carboplatin dose was calculated to reach a target area under the curve (AUC) of concentration x time according to the Calvert formula. Gemcitabine 1000 mg/m^2 was administered IV on Days 1 and Day 8 of each of the six 21-day treatment cycles. Bevacizumab 15 mg/kg was administered IV on Day 1 of each of the six 21-day treatment cycles. The bevacizumab dose was based on the patient's weight at baseline and remained the same throughout the study.	Carboplatin (AUC 4 mg/mL/minute) was administered intravenously (IV) on Day 1 of each of six 21-day treatment cycles. The carboplatin dose was calculated to reach a target area under the curve (AUC) of concentration x time according to the Calvert formula. Gemcitabine 1000 mg/m^2 was administered IV on Days 1 and Day 8 of each of the six 21-day treatment cycles. Placebo was administered by IV on Day 1 of each of the six 21-day treatment cycles.
Overall Number of Participants Analyzed	247	233
Measure Type: Number; Unit of Measure: Percentage of participants
	100.0	100.0

Adverse Events

Time Frame	From randomization through July 19, 2013
Adverse Event Reporting Description	Safety population: All patients who received at least 1 dose of protocol treatment. Due to errors in drug administration, the safety population included 247 patients in the carboplatin and gemcitabine + bevacizumab group and 233 patients in the carboplatin and gemcitabine + placebo group.
Arm/Group Title	Carboplatin and Gemcitabine + Bevacizumab	Carboplatin and Gemcitabine + Placebo
Arm/Group Description	Carboplatin (AUC 4 mg/mL/minute) was administered intravenously (IV) on Day 1 of each of six 21-day treatment cycles. The carboplatin dose was calculated to reach a target area under the curve (AUC) of concentration x time according to the Calvert formula. Gemcitabine 1000 mg/m^2 was administered IV on Days 1 and Day 8 of each of the six 21-day treatment cycles. Bevacizumab 15 mg/kg was administered IV on Day 1 of each of the six 21-day treatment cycles. The bevacizumab dose was based on the patient's weight at baseline and remained the same throughout the study.	Carboplatin (AUC 4 mg/mL/minute) was administered intravenously (IV) on Day 1 of each of six 21-day treatment cycles. The carboplatin dose was calculated to reach a target area under the curve (AUC) of concentration x time according to the Calvert formula. Gemcitabine 1000 mg/m^2 was administered IV on Days 1 and Day 8 of each of the six 21-day treatment cycles. Placebo was administered by IV on Day 1 of each of the six 21-day treatment cycles.
All-Cause Mortality
	Carboplatin and Gemcitabine + Bevacizumab	Carboplatin and Gemcitabine + Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events
	Carboplatin and Gemcitabine + Bevacizumab	Carboplatin and Gemcitabine + Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	90/247 (36.44%)	59/233 (25.32%)
Blood and lymphatic system disorders
Anaemia † 1	6/247 (2.43%)	1/233 (0.43%)
Febrile Neutropenia † 1	2/247 (0.81%)	4/233 (1.72%)
Haemolytic Uraemic Syndrome † 1	0/247 (0.00%)	1/233 (0.43%)
Leukocytosis † 1	0/247 (0.00%)	1/233 (0.43%)
Leukopenia † 1	1/247 (0.40%)	0/233 (0.00%)
Neutropenia † 1	1/247 (0.40%)	3/233 (1.29%)
Pancytopenia † 1	1/247 (0.40%)	0/233 (0.00%)
Thrombocytopenia † 1	8/247 (3.24%)	8/233 (3.43%)
Cardiac disorders
Acute Myocardial Infarction † 1	0/247 (0.00%)	1/233 (0.43%)
Cardiac Failure † 1	1/247 (0.40%)	0/233 (0.00%)
Cardiac Failure Congestive † 1	1/247 (0.40%)	2/233 (0.86%)
Cardiomyopathy † 1	1/247 (0.40%)	0/233 (0.00%)
Myocardial Infarction † 1	1/247 (0.40%)	0/233 (0.00%)
Supraventricular Tachycardia † 1	1/247 (0.40%)	0/233 (0.00%)
Gastrointestinal disorders
Abdominal Pain † 1	3/247 (1.21%)	2/233 (0.86%)
Abdominal Pain Lower † 1	0/247 (0.00%)	1/233 (0.43%)
Abdominal Pain Upper † 1	0/247 (0.00%)	1/233 (0.43%)
Ascites † 1	0/247 (0.00%)	1/233 (0.43%)
Constipation † 1	0/247 (0.00%)	2/233 (0.86%)
Diarrhoea † 1	1/247 (0.40%)	1/233 (0.43%)
Duodenal Ulcer † 1	1/247 (0.40%)	0/233 (0.00%)
Gastric Ulcer † 1	1/247 (0.40%)	0/233 (0.00%)
Gastritis † 1	2/247 (0.81%)	0/233 (0.00%)
Haemorrhoids † 1	1/247 (0.40%)	0/233 (0.00%)
Ileus † 1	1/247 (0.40%)	2/233 (0.86%)
Ileus Spastic † 1	1/247 (0.40%)	0/233 (0.00%)
Intestinal Obstruction † 1	3/247 (1.21%)	1/233 (0.43%)
Nausea † 1	3/247 (1.21%)	0/233 (0.00%)
Small Intestinal Obstruction † 1	4/247 (1.62%)	6/233 (2.58%)
Upper Gastrointestinal Haemorrhage † 1	0/247 (0.00%)	1/233 (0.43%)
Vomiting † 1	2/247 (0.81%)	3/233 (1.29%)
General disorders
Adverse Drug Reaction † 1	1/247 (0.40%)	1/233 (0.43%)
Infusion Related Reaction † 1	1/247 (0.40%)	0/233 (0.00%)
Pyrexia † 1	2/247 (0.81%)	6/233 (2.58%)
Thrombosis In Device † 1	0/247 (0.00%)	1/233 (0.43%)
Influenza Like Illness † 2	1/247 (0.40%)	0/233 (0.00%)
Hepatobiliary disorders
Bile Duct Obstruction † 1	0/247 (0.00%)	1/233 (0.43%)
Biliary Colic † 1	1/247 (0.40%)	0/233 (0.00%)
Cholecystitis † 1	1/247 (0.40%)	3/233 (1.29%)
Cholecystitis Acute † 1	1/247 (0.40%)	0/233 (0.00%)
Cholelithiasis † 2	1/247 (0.40%)	0/233 (0.00%)
Immune system disorders
Drug Hypersensitivity † 1	4/247 (1.62%)	3/233 (1.29%)
Hypersensitivity † 1	1/247 (0.40%)	1/233 (0.43%)
Infections and infestations
Bacteraemia † 1	1/247 (0.40%)	0/233 (0.00%)
Catheter Site Infection † 1	1/247 (0.40%)	0/233 (0.00%)
Cellulitis † 1	2/247 (0.81%)	2/233 (0.86%)
Device Related Infection † 1	1/247 (0.40%)	0/233 (0.00%)
Diverticulitis † 1	1/247 (0.40%)	1/233 (0.43%)
Infection † 1	1/247 (0.40%)	0/233 (0.00%)
Kidney Infection † 1	1/247 (0.40%)	0/233 (0.00%)
Pneumonia † 1	3/247 (1.21%)	2/233 (0.86%)
Thrombophlebitis Septic † 1	1/247 (0.40%)	0/233 (0.00%)
Urinary Tract Infection † 1	0/247 (0.00%)	1/233 (0.43%)
Urosepsis † 1	0/247 (0.00%)	1/233 (0.43%)
Viral Infection † 1	1/247 (0.40%)	0/233 (0.00%)
Appendicitis † 2	1/247 (0.40%)	0/233 (0.00%)
Injury, poisoning and procedural complications
Overdose † 1	1/247 (0.40%)	0/233 (0.00%)
Patella Fracture † 1	1/247 (0.40%)	0/233 (0.00%)
Wound Complication † 1	1/247 (0.40%)	0/233 (0.00%)
Femur Fracture † 2	1/247 (0.40%)	0/233 (0.00%)
Incisional Hernia † 1	0/247 (0.00%)	1/233 (0.43%)
Metabolism and nutrition disorders
Dehydration † 1	2/247 (0.81%)	3/233 (1.29%)
Musculoskeletal and connective tissue disorders
Arthritis † 1	1/247 (0.40%)	0/233 (0.00%)
Back Pain † 1	1/247 (0.40%)	0/233 (0.00%)
Musculoskeletal Chest Pain † 1	2/247 (0.81%)	0/233 (0.00%)
Pain In Extremity † 1	0/247 (0.00%)	1/233 (0.43%)
Soft Tissue Haemorrhage † 1	1/247 (0.40%)	0/233 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Glioblastoma † 1	1/247 (0.40%)	0/233 (0.00%)
Squamous Cell Carcinoma † 1	1/247 (0.40%)	0/233 (0.00%)
Papillary Thyroid Cancer † 1	0/247 (0.00%)	1/233 (0.43%)
Tumour Compression † 1	0/247 (0.00%)	1/233 (0.43%)
Basal Cell Carcinoma † 2	1/247 (0.40%)	0/233 (0.00%)
Breast Cancer † 1	1/247 (0.40%)	0/233 (0.00%)
Colorectal Cancer Metastatic † 1	1/247 (0.40%)	0/233 (0.00%)
Nervous system disorders
Cerebral Ischaemia † 1	0/247 (0.00%)	1/233 (0.43%)
Cerebrovascular Accident † 1	0/247 (0.00%)	1/233 (0.43%)
Convulsion † 1	0/247 (0.00%)	1/233 (0.43%)
Dizziness † 1	0/247 (0.00%)	1/233 (0.43%)
Encephalopathy † 1	1/247 (0.40%)	0/233 (0.00%)
Haemorrhage Intracranial † 1	1/247 (0.40%)	0/233 (0.00%)
Haemorrhagic Stroke † 1	1/247 (0.40%)	0/233 (0.00%)
Headache † 1	1/247 (0.40%)	0/233 (0.00%)
Migraine † 1	1/247 (0.40%)	0/233 (0.00%)
Peripheral Motor Neuropathy † 1	0/247 (0.00%)	1/233 (0.43%)
Reversible Posterior Leukoencephalopathy Syndrome † 1	2/247 (0.81%)	0/233 (0.00%)
Speech Disorder † 1	1/247 (0.40%)	0/233 (0.00%)
Syncope † 1	2/247 (0.81%)	1/233 (0.43%)
Transient Ischaemic Attack † 1	1/247 (0.40%)	0/233 (0.00%)
Tremor † 1	0/247 (0.00%)	1/233 (0.43%)
Psychiatric disorders
Mental Status Changes † 1	2/247 (0.81%)	0/233 (0.00%)
Renal and urinary disorders
Haematuria † 1	1/247 (0.40%)	0/233 (0.00%)
Hydronephrosis † 1	1/247 (0.40%)	1/233 (0.43%)
Nephrotic Syndrome † 1	1/247 (0.40%)	1/233 (0.43%)
Renal Failure Acute † 1	1/247 (0.40%)	0/233 (0.00%)
Ureteric Obstruction † 1	0/247 (0.00%)	1/233 (0.43%)
Reproductive system and breast disorders
Female Genital Tract Fistula † 1	1/247 (0.40%)	0/233 (0.00%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea † 1	2/247 (0.81%)	3/233 (1.29%)
Epistaxis † 1	5/247 (2.02%)	1/233 (0.43%)
Hypoxia † 1	1/247 (0.40%)	0/233 (0.00%)
Pneumothorax † 1	0/247 (0.00%)	1/233 (0.43%)
Pulmonary Embolism † 1	2/247 (0.81%)	3/233 (1.29%)
Surgical and medical procedures
Ureteral Stent Insertion † 1	1/247 (0.40%)	0/233 (0.00%)
Vascular disorders
Arterial Thrombosis † 1	1/247 (0.40%)	0/233 (0.00%)
Deep Vein Thrombosis † 1	2/247 (0.81%)	1/233 (0.43%)
Embolism † 1	1/247 (0.40%)	0/233 (0.00%)
Hypertension † 1	4/247 (1.62%)	0/233 (0.00%)
Malignant Hypertension † 1	2/247 (0.81%)	0/233 (0.00%)
Thrombophlebitis † 1	0/247 (0.00%)	1/233 (0.43%)
Thrombophlebitis Superficial † 1	1/247 (0.40%)	0/233 (0.00%)
Thrombosis † 1	2/247 (0.81%)	0/233 (0.00%)
Vena Cava Thrombosis † 1	1/247 (0.40%)	0/233 (0.00%)
Embolism Venous † 1	1/247 (0.40%)	0/233 (0.00%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 16.0; 2 Term from vocabulary, MedDRA
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Carboplatin and Gemcitabine + Bevacizumab	Carboplatin and Gemcitabine + Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	246/247 (99.60%)	233/233 (100.00%)
Blood and lymphatic system disorders
Anaemia † 1	126/247 (51.01%)	137/233 (58.80%)
Leukopenia † 1	36/247 (14.57%)	32/233 (13.73%)
Neutropenia † 1	172/247 (69.64%)	158/233 (67.81%)
Thrombocytopenia † 1	135/247 (54.66%)	111/233 (47.64%)
Ear and labyrinth disorders
Tinnitus † 1	14/247 (5.67%)	11/233 (4.72%)
Eye disorders
Vision Blurred † 1	14/247 (5.67%)	17/233 (7.30%)
Gastrointestinal disorders
Abdominal Discomfort † 1	15/247 (6.07%)	15/233 (6.44%)
Abdominal Distension † 1	24/247 (9.72%)	21/233 (9.01%)
Abdominal Pain † 1	60/247 (24.29%)	58/233 (24.89%)
Abdominal Pain Lower † 1	20/247 (8.10%)	16/233 (6.87%)
Abdominal Pain Upper † 1	19/247 (7.69%)	17/233 (7.30%)
Constipation † 1	132/247 (53.44%)	122/233 (52.36%)
Diarrhoea † 1	95/247 (38.46%)	67/233 (28.76%)
Dyspepsia † 1	27/247 (10.93%)	29/233 (12.45%)
Gastrooesophageal Reflux Disease † 1	20/247 (8.10%)	17/233 (7.30%)
Gingival Bleeding † 1	17/247 (6.88%)	1/233 (0.43%)
Haemorrhoids † 1	18/247 (7.29%)	6/233 (2.58%)
Nausea † 1	177/247 (71.66%)	153/233 (65.67%)
Rectal Haemorrhage † 1	21/247 (8.50%)	10/233 (4.29%)
Stomatitis † 1	39/247 (15.79%)	16/233 (6.87%)
Vomiting † 1	81/247 (32.79%)	66/233 (28.33%)
Oral Pain † 1	13/247 (5.26%)	3/233 (1.29%)
General disorders
Asthenia † 1	25/247 (10.12%)	27/233 (11.59%)
Catheter Site Pain † 1	14/247 (5.67%)	6/233 (2.58%)
Chest Pain † 1	19/247 (7.69%)	9/233 (3.86%)
Chills † 1	28/247 (11.34%)	22/233 (9.44%)
Fatigue † 1	201/247 (81.38%)	175/233 (75.11%)
Mucosal Inflammation † 1	38/247 (15.38%)	25/233 (10.73%)
Oedema Peripheral † 1	41/247 (16.60%)	46/233 (19.74%)
Pain † 1	26/247 (10.53%)	28/233 (12.02%)
Pyrexia † 1	41/247 (16.60%)	37/233 (15.88%)
Immune system disorders
Drug Hypersensitivity † 1	26/247 (10.53%)	15/233 (6.44%)
Hypersensitivity † 1	16/247 (6.48%)	12/233 (5.15%)
Infections and infestations
Nasopharyngitis † 1	21/247 (8.50%)	17/233 (7.30%)
Sinusitis † 1	38/247 (15.38%)	21/233 (9.01%)
Upper Respiratory Tract Infection † 1	42/247 (17.00%)	28/233 (12.02%)
Urinary Tract Infection † 1	37/247 (14.98%)	39/233 (16.74%)
Injury, poisoning and procedural complications
Contusion † 1	43/247 (17.41%)	21/233 (9.01%)
Investigations
Alanine Aminotransferase Increased † 1	14/247 (5.67%)	19/233 (8.15%)
Aspartate Aminotransferase Increased † 1	12/247 (4.86%)	17/233 (7.30%)
Haemoglobin Decreased † 1	30/247 (12.15%)	21/233 (9.01%)
Neutrophil Count Decreased † 1	29/247 (11.74%)	23/233 (9.87%)
Platelet Count Decreased † 1	22/247 (8.91%)	24/233 (10.30%)
White Blood Cell Count Decreased † 1	13/247 (5.26%)	19/233 (8.15%)
Blood Creatinine Increased † 1	13/247 (5.26%)	9/233 (3.86%)
Metabolism and nutrition disorders
Decreased Appetite † 1	48/247 (19.43%)	61/233 (26.18%)
Dehydration † 1	18/247 (7.29%)	13/233 (5.58%)
Hyperglycaemia † 1	23/247 (9.31%)	17/233 (7.30%)
Hypokalaemia † 1	24/247 (9.72%)	26/233 (11.16%)
Hypomagnesaemia † 1	39/247 (15.79%)	35/233 (15.02%)
Hypocalcaemia † 1	13/247 (5.26%)	8/233 (3.43%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	69/247 (27.94%)	44/233 (18.88%)
Back Pain † 1	51/247 (20.65%)	32/233 (13.73%)
Bone Pain † 1	29/247 (11.74%)	25/233 (10.73%)
Muscle Spasms † 1	21/247 (8.50%)	14/233 (6.01%)
Muscular Weakness † 1	9/247 (3.64%)	12/233 (5.15%)
Musculoskeletal Pain † 1	22/247 (8.91%)	15/233 (6.44%)
Myalgia † 1	42/247 (17.00%)	33/233 (14.16%)
Neck Pain † 1	15/247 (6.07%)	14/233 (6.01%)
Pain In Extremity † 1	40/247 (16.19%)	35/233 (15.02%)
Nervous system disorders
Dizziness † 1	58/247 (23.48%)	38/233 (16.31%)
Dysgeusia † 1	31/247 (12.55%)	32/233 (13.73%)
Headache † 1	119/247 (48.18%)	70/233 (30.04%)
Neuropathy Peripheral † 1	45/247 (18.22%)	48/233 (20.60%)
Peripheral Sensory Neuropathy † 1	13/247 (5.26%)	18/233 (7.73%)
Hypoaesthesia † 1	9/247 (3.64%)	12/233 (5.15%)
Psychiatric disorders
Anxiety † 1	33/247 (13.36%)	18/233 (7.73%)
Depression † 1	37/247 (14.98%)	24/233 (10.30%)
Insomnia † 1	51/247 (20.65%)	36/233 (15.45%)
Renal and urinary disorders
Dysuria † 1	13/247 (5.26%)	15/233 (6.44%)
Proteinuria † 1	52/247 (21.05%)	8/233 (3.43%)
Respiratory, thoracic and mediastinal disorders
Cough † 1	66/247 (26.72%)	43/233 (18.45%)
Dysphonia † 1	34/247 (13.77%)	8/233 (3.43%)
Dyspnoea † 1	74/247 (29.96%)	53/233 (22.75%)
Dyspnoea Exertional † 1	22/247 (8.91%)	21/233 (9.01%)
Epistaxis † 1	130/247 (52.63%)	32/233 (13.73%)
Nasal Congestion † 1	20/247 (8.10%)	18/233 (7.73%)
Oropharyngeal Pain † 1	40/247 (16.19%)	23/233 (9.87%)
Rhinorrhoea † 1	26/247 (10.53%)	9/233 (3.86%)
Sinus Congestion † 1	19/247 (7.69%)	4/233 (1.72%)
Skin and subcutaneous tissue disorders
Alopecia † 1	64/247 (25.91%)	64/233 (27.47%)
Erythema † 1	14/247 (5.67%)	12/233 (5.15%)
Pruritus † 1	35/247 (14.17%)	28/233 (12.02%)
Rash † 1	53/247 (21.46%)	51/233 (21.89%)
Dry Skin † 1	13/247 (5.26%)	6/233 (2.58%)
Petechiae † 1	13/247 (5.26%)	4/233 (1.72%)
Vascular disorders
Flushing † 1	15/247 (6.07%)	9/233 (3.86%)
Hot Flush † 1	19/247 (7.69%)	13/233 (5.58%)
Hypertension † 1	102/247 (41.30%)	20/233 (8.58%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 16.0

Limitations and Caveats

[Not Specified]

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.

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.

Results Point of Contact

• Name/Title: Medical Communications
• Organization: Hoffman-LaRoche
• Phone: 800-821-8590

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

Aghajanian C, Goff B, Nycum LR, Wang YV, Husain A, Blank SV. Final overall survival and safety analysis of OCEANS, a phase 3 trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent ovarian cancer. Gynecol Oncol. 2015 Oct;139(1):10-6. doi: 10.1016/j.ygyno.2015.08.004. Epub 2015 Aug 10.

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.

• Responsible Party: Genentech, Inc.
• ClinicalTrials.gov Identifier: NCT00434642
• Other Study ID Numbers: AVF4095g
• First Submitted: February 9, 2007
• First Posted: February 13, 2007
• Results First Submitted: September 26, 2011
• Results First Posted: November 3, 2011
• Last Update Posted: August 9, 2017