A Study of Carboplatin and Gemcitabine Plus Bevacizumab i... | NCT00434642

A Study of Carboplatin and Gemcitabine Plus Bevacizumab i... | NCT00434642 | Trialant

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Carboplatin and gemcitabine + bevacizumab	Experimental	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.	Drug: Carboplatin Drug: Gemcitabine Drug: Bevacizumab
Carboplatin and gemcitabine + placebo	Active Comparator	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.	Drug: Carboplatin Drug: Gemcitabine Drug: Placebo

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Carboplatin	Drug	Carboplatin was provided as commercially available drug.	Carboplatin and gemcitabine + bevacizumab Carboplatin and gemcitabine + placebo

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Progression Free Survival (PFS) as Determined by the Investigator, Per Response Evaluation Criteria for Solid Tumors (RECIST)	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.	From randomization through September 17, 2010 (up to 3 years, 5 months)

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Patients With an Objective Response as Determined by the Investigator, Per Response Evaluation Criteria for Solid Tumors (RECIST)	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.

Name	Affiliation	Role
Amreen Husain, MD	Genentech, Inc.	Study Director

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
37185961	Derived	Gaitskell K, Rogozinska E, Platt S, Chen Y, Abd El Aziz M, Tattersall A, Morrison J. Angiogenesis inhibitors for the treatment of epithelial ovarian cancer. Cochrane Database Syst Rev. 2023 Apr 18;4(4):CD007930. doi: 10.1002/14651858.CD007930.pub3.
26271155	Derived	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.

Arm/Group Information

ID	Title	Description
FG000	Carboplatin and Gemcitabine + Placebo	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.
FG001	Carboplatin and Gemcitabine + Bevacizumab	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.

Periods

Title

Milestones

Reasons Not Completed

Blinded Treatment Phase

Type	Comment	Milestone Data
STARTED		FG000242 subjects FG001242 subjects
COMPLETED		FG0000 subjects FG00113 subjects
NOT COMPLETED		FG000242 subjects FG001229 subjects

Type	Comment	Reasons
Adverse Event		FG00012 subjects FG00158 subjects
Clinical Disease Progression		FG0004 subjects FG001

Open-label Treatment Phase

Type	Comment	Milestone Data
STARTED		FG0000 subjects FG00112 subjectsOne participant did not continue into the open-label treatment phase.
COMPLETED		FG0000 subjects

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Carboplatin and Gemcitabine + Placebo	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.

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Progression Free Survival (PFS) as Determined by the Investigator, Per Response Evaluation Criteria for Solid Tumors (RECIST)

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.

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

Posted

Median

95% Confidence Interval

Months

From randomization through September 17, 2010 (up to 3 years, 5 months)

ID	Title	Description
OG000	Carboplatin and Gemcitabine + Bevacizumab

Adverse Events Module

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	Carboplatin and Gemcitabine + Bevacizumab	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.

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 16.0	Systematic Assessment

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 16.0	Systematic Assessment

More Info Module

Certain Agreements

Title	Organization	Phone	Extension	Email
Medical Communications	Hoffman-LaRoche	800-821-8590

Condition Browse Module

ID	Term
D010051	Ovarian Neoplasms
D005185	Fallopian Tube Neoplasms

ID	Term
D004701	Endocrine Gland Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D010049	Ovarian Diseases

Intervention Browse Module

ID	Term
D016190	Carboplatin
D000093542	Gemcitabine
D000068258	Bevacizumab

ID	Term
D056831	Coordination Complexes
D009930	Organic Chemicals
D006571	Heterocyclic Compounds
D003841	Deoxycytidine

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	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.	Log Rank	The analysis was stratified for time since the last platinum therapy (6-12, > 12 months) and cytoreductive surgery for recurrent disease (yes, no).	<0.0001	A P-value < 0.05 was required for significance.	Hazard Ratio (HR)	0.484			2-Sided	95	0.388	0.605			The hazard ratio was estimated using Cox regression. The hazard ratio is relative to the carboplatin and gemcitabine + placebo group.		Superiority or Other

Secondary

Percentage of Patients With an Objective Response as Determined by the Investigator, Per Response Evaluation Criteria for Solid Tumors (RECIST)

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.

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

Posted

Number

Percentage of participants

From randomization through September 17, 2010 (up to 3 years, 5 months)

ID	Title	Description
OG000	Carboplatin and Gemcitabine + Bevacizumab	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.
OG001	Carboplatin and Gemcitabine + Placebo	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.

Units	Counts
Participants	OG000242 OG001242

Title

Denominators

Categories

Title	Measurements
	OG00078.5 OG00157.4

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	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.	Cochran-Mantel-Haenszel	The analysis was stratified for time since the last platinum therapy (6-12, > 12 months) and cytoreductive surgery for recurrent disease (yes, no).	<0.0001	A P-value < 0.05 was required for significance.	Mean Difference (Final Values)	21.1			2-Sided	95	13.0	29.2			The difference in response rates and the 95% confidence intervals for response rates were computed using the normal approximation to the binomial distribution.

Secondary

Duration of Objective Response (OR) as Determined by the Investigator, Per Response Evaluation Criteria for Solid Tumors (RECIST)

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.

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

Posted

Median

95% Confidence Interval

Months

From randomization through September 17, 2010 (up to 3 years, 5 months)

ID	Title	Description
OG000	Carboplatin and Gemcitabine + Bevacizumab	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.
OG001	Carboplatin and Gemcitabine + Placebo	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.

Units	Counts
Participants	OG000190 OG001139

Title

Denominators

Categories

Title	Measurements
	OG00010.4(9.36 to 11.83) OG0017.4(6.31 to 8.31)

Secondary

Overall Survival

Overall survival was defined as the time from randomization to death from any cause.

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

Posted

Median

95% Confidence Interval

Months

From randomization through July 19, 2013 (up to 6 years, 3 months)

ID	Title	Description
OG000	Carboplatin and Gemcitabine + Bevacizumab	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.
OG001	Carboplatin and Gemcitabine + Placebo	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.

Units	Counts
Participants	OG000242 OG001242

Title

Denominators

Categories

Title	Measurements
	OG00033.6(30.32 to 35.84) OG00132.9(29.80 to 37.68)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Log Rank	The analysis was stratified for time since the last platinum therapy (≤12, >12 months) and cytoreductive surgery for recurrent disease (Yes, No).	0.6479	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.	Hazard Ratio (HR)	0.952			2-Sided	95	0.771	1.176			The hazard ratio was estimated using Cox regression. The hazard ratio is relative to the carboplatin and gemcitabine + placebo group.

Secondary

Percentage of Patients Who Had a Gastrointestinal Perforation (GIP)

A gastrointestinal perforation is a hole that develops through the entire wall of the stomach, small intestine, large bowel, or gallbladder.

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.

Posted

Number

Percentage of participants

From randomization through September 17, 2010 (up to 3 years, 5 months)

ID	Title	Description
OG000	Carboplatin and Gemcitabine + Bevacizumab	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.
OG001	Carboplatin and Gemcitabine + Placebo	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.

Units	Counts
Participants	OG000247 OG001233

Title

Denominators

Categories

Title	Measurements
	OG0000 OG0010

Secondary

Percentage of Patients Who Had at Least 1 Adverse Event

Posted

Number

Percentage of participants

From randomization through July 19, 2013 (up to 6 years, 3 months)

ID	Title	Description
OG000	Carboplatin and Gemcitabine + Bevacizumab	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.
OG001	Carboplatin and Gemcitabine + Placebo	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.

Units	Counts
Participants	OG000247 OG001233

Title

Denominators

Categories

Title	Measurements
	OG000100.0 OG001100.0