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Trial record 1 of 1 for:    NCT00976911
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AURELIA: A Study of Avastin (Bevacizumab) Added to Chemotherapy in Patients With Platinum-resistant Ovarian Cancer

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ClinicalTrials.gov Identifier: NCT00976911
Recruitment Status : Completed
First Posted : September 15, 2009
Results First Posted : February 25, 2015
Last Update Posted : February 25, 2015
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Ovarian Cancer
Interventions Drug: bevacizumab [Avastin]
Drug: liposomal doxorubicin
Drug: paclitaxel
Drug: topotecan
Enrollment 361
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Chemotherapy Chemotherapy + Bevacizumab
Hide Arm/Group Description Participants received one of the following chemotherapies at the discretion of the investigator: paclitaxel, 80 milligrams per square meter (mg/m^2) as a 1-hour intravenous (IV) infusion on Days 1, 8, 15, and 22 every 4 weeks (q4w) OR topotecan 4 mg/m^2 as a 30-minute IV infusion on Days 1, 8, and 15 q4w (alternatively, a 1.25 mg/m^2 dose could have been administered over 30 minutes on Days 1-5 every 3 weeks [q3w]) OR pegylated liposomal doxorubicin (PLD) 40 mg/m^2 as a 1 milligram per minute (mg/min) infusion on Day 1 q4w (after Cycle 1 the drug could have been administered as a 1 hour infusion). Depending on chosen chemotherapy, pre-medication was implemented according to local practices. Participants received one of the following chemotherapies at the discretion of the investigator: paclitaxel, 80 mg/m^2 as a 1-hour IV infusion on Days 1, 8, 15, and 22 q4w OR topotecan 4 mg/m^2 as a 30-minute IV infusion on Days 1, 8, and 15 q4w (alternatively, a 1.25 mg/m^2 dose could have been administered over 30 minutes on Days 1-5 q3w) OR PLD 40 mg/m^2 as a 1 mg/min infusion on Day 1 q4w (after Cycle 1 the drug could have been administered as a 1 hour infusion. Depending on chosen chemotherapy, pre-medication was implemented according to local practices. The chosen chemotherapy was combined with bevacizumab 10 milligrams per kilogram (mg/kg) IV every 2 weeks (q2w; or bevacizumab 15 mg/kg q3w if used in combination with topotecan 1.25 mg/m^2 on Days 1-5 on a q3w schedule). The initial bevacizumab infusion was over 90 minutes, with subsequent infusions over 60 minutes and then 30 minutes, as tolerated.
Period Title: Overall Study
Started 182 179
Completed 0 [1] 0 [1]
Not Completed 182 179
Reason Not Completed
Withdrawal by Subject             4             6
Death             138             126
Adverse Event             0             1
Protocol Violation             2             0
Not Specified             8             9
In Follow-Up as of 25 Jan 2013             30             37
[1]
At time of clinical cutoff for overall survival and safety (25 January 2013)
Arm/Group Title Chemotherapy Chemotherapy + Bevacizumab Total
Hide Arm/Group Description Participants received one of the following chemotherapies at the discretion of the investigator: paclitaxel, 80 mg/m^2 as a 1-hour IV infusion on Days 1, 8, 15, and 22 q4w OR topotecan 4 mg/m^2 as a 30-minute IV infusion on Days 1, 8, and 15 q4w (alternatively, a 1.25 mg/m^2 dose could have been administered over 30 minutes on Days 1-5 q3w) OR PLD 40 mg/m^2 as a 1 mg/min infusion on Day 1 q4w (after Cycle 1 the drug could have been administered as a 1 hour infusion). Depending on chosen chemotherapy, pre-medication was implemented according to local practices. Participants received one of the following chemotherapies at the discretion of the investigator: paclitaxel, 80 mg/m^2 as a 1-hour IV infusion on Days 1, 8, 15, and 22 q4w OR topotecan 4 mg/m^2 as a 30-minute IV infusion on Days 1, 8, and 15 q4w (alternatively, a 1.25 mg/m^2 dose could have been administered over 30 minutes on Days 1-5 q3w) OR PLD 40 mg/m^2 as a 1 mg/min infusion on Day 1 q4w (after Cycle 1 the drug could have been administered as a 1 hour infusion). Depending on chosen chemotherapy, pre-medication was implemented according to local practices. The chosen chemotherapy was combined with bevacizumab 10 mg/kg IV q2w (or bevacizumab 15 mg/kg q3w if used in combination with topotecan 1.25 mg/m^2 on Days 1-5 on a q3w schedule). The initial bevacizumab infusion was over 90 minutes, with subsequent infusions over 60 minutes and then 30 minutes, as tolerated. Total of all reporting groups
Overall Number of Baseline Participants 182 179 361
Hide Baseline Analysis Population Description
All randomized participants
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 182 participants 179 participants 361 participants
60.7  (9.8) 60.0  (11.1) 60.3  (10.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 182 participants 179 participants 361 participants
Female
182
 100.0%
179
 100.0%
361
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Percentage of Participants With Disease Progression or Death (Data Cutoff 14 November 2011)
Hide Description Progression free survival was defined as the time from the date of randomization to the first documented disease progression or death, whichever occurs first. Progression was based on tumour assessment made by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST) criteria (for participants with measurable disease), and for those with non-measurable disease presence or absence of lesions was noted.
Time Frame Screening Visit, Every 8 weeks (or 9 weeks if receiving topotecan) until progression reported between day of first participant randomized (29 October 2009) until cutoff date of 14 November 2011
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population: All participants randomized to study treatment, irrespective of whether or not the assigned treatment was actually received. For all efficacy analyses, participants were grouped according to the treatment assigned at randomization
Arm/Group Title Chemotherapy Chemotherapy + Bevacizumab
Hide Arm/Group Description:
Participants received one of the following chemotherapies at the discretion of the investigator: paclitaxel, 80 mg/m^2 as a 1-hour IV infusion on Days 1, 8, 15, and 22 q4w OR topotecan 4 mg/m^2 as a 30-minute IV infusion on Days 1, 8, and 15 q4w (alternatively, a 1.25 mg/m^2 dose could have been administered over 30 minutes on Days 1-5 q3w) OR PLD 40 mg/m^2 as a 1 mg/min infusion on Day 1 q4w (after Cycle 1 the drug could have been administered as a 1 hour infusion). Depending on chosen chemotherapy, pre-medication was implemented according to local practices.
Participants received one of the following chemotherapies at the discretion of the investigator: paclitaxel, 80 mg/m^2 as a 1-hour IV infusion on Days 1, 8, 15, and 22 q4w OR topotecan 4 mg/m^2 as a 30-minute IV infusion on Days 1, 8, and 15 q4w (alternatively, a 1.25 mg/m^2 dose could have been administered over 30 minutes on Days 1-5 q3w) OR PLD 40 mg/m^2 as a 1 mg/min infusion on Day 1 q4w (after Cycle 1 the drug could have been administered as a 1 hour infusion). Depending on chosen chemotherapy, pre-medication was implemented according to local practices. The chosen chemotherapy was combined with bevacizumab 10 mg/kg IV q2w (or bevacizumab 15 mg/kg q3w if used in combination with topotecan 1.25 mg/m^2 on Days 1-5 on a q3w schedule). The initial bevacizumab infusion was over 90 minutes, with subsequent infusions over 60 minutes and then 30 minutes, as tolerated.
Overall Number of Participants Analyzed 182 179
Measure Type: Number
Unit of Measure: percentage of participants
92.3 78.8
2.Primary Outcome
Title Progression Free Survival (PFS; Data Cutoff 14 November 2011)
Hide Description PFS was defined as the time from the date of randomization to the first documented disease progression or death, whichever occurred first. Progression was based on tumor assessment made by the investigators according to the RECIST criteria (for participants with measurable disease), and for those with non-measurable disease presence or absence of lesions was noted. Time from randomization to occurrence of disease progression or death was measured in months. An event was defined as the earliest progressive disease or death that occurred on or before the cutoff date (14 November 2011), regardless of start of nonprotocol specified anti-cancer therapy or the bevacizumab monotherapy. Disease progression was assessed by investigator according to RECIST or by symptom deterioration, and could not be declared on the basis of rising cancer antigen 125 (CA125) levels alone. Kaplan-Meier methodology was used. 95% CI for median was computed using the method of Brookmeyer and Crowley.
Time Frame Screening Visit, Every 8 weeks (or 9 weeks if receiving topotecan) until progression reported between day of first participant randomized (29 October 2009) until cutoff date of 14 November 2011
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population; only participants with an event of progression or death were included in the analysis
Arm/Group Title Chemotherapy Chemotherapy + Bevacizumab
Hide Arm/Group Description:
Participants received one of the following chemotherapies at the discretion of the investigator: paclitaxel, 80 mg/m^2 as a 1-hour IV infusion on Days 1, 8, 15, and 22 q4w OR topotecan 4 mg/m^2 as a 30-minute IV infusion on Days 1, 8, and 15 q4w (alternatively, a 1.25 mg/m^2 dose could have been administered over 30 minutes on Days 1-5 q3w) OR PLD 40 mg/m^2 as a 1 mg/min infusion on Day 1 q4w (after Cycle 1 the drug could have been administered as a 1 hour infusion). Depending on chosen chemotherapy, pre-medication was implemented according to local practices.
Participants received one of the following chemotherapies at the discretion of the investigator: paclitaxel, 80 mg/m^2 as a 1-hour IV infusion on Days 1, 8, 15, and 22 q4w OR topotecan 4 mg/m^2 as a 30-minute IV infusion on Days 1, 8, and 15 q4w (alternatively, a 1.25 mg/m^2 dose could have been administered over 30 minutes on Days 1-5 q3w) OR PLD 40 mg/m^2 as a 1 mg/min infusion on Day 1 q4w (after Cycle 1 the drug could have been administered as a 1 hour infusion). Depending on chosen chemotherapy, pre-medication was implemented according to local practices. The chosen chemotherapy was combined with bevacizumab 10 mg/kg IV q2w (or bevacizumab 15 mg/kg q3w if used in combination with topotecan 1.25 mg/m^2 on Days 1-5 on a q3w schedule). The initial bevacizumab infusion was over 90 minutes, with subsequent infusions over 60 minutes and then 30 minutes, as tolerated.
Overall Number of Participants Analyzed 168 141
Median (95% Confidence Interval)
Unit of Measure: months
3.4
(2.10 to 3.75)
6.7
(5.62 to 7.79)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Chemotherapy, Chemotherapy + Bevacizumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.379
Confidence Interval (2-Sided) 95%
0.296 to 0.485
Estimation Comments Stratified analysis:Strata were chemotherapy selected (paclitaxel, PLD, or topotecan), prior anti-angiogenic therapy (yes or no), and platinum-free interval (less than [<] 3 or 3-6 months). Cox regression model was used to determine the hazard ratio.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Chemotherapy, Chemotherapy + Bevacizumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Log Rank
Comments Unstratified analysis
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.460
Confidence Interval (2-Sided) 95%
0.366 to 0.577
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Chemotherapy, Chemotherapy + Bevacizumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Peto-Peto-Prentice
Comments Unstratified analysis
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Chemotherapy, Chemotherapy + Bevacizumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Peto-Peto-Prentice
Comments Stratified analysis:Strata were chemotherapy selected, prior anti-angiogenic therapy, and platinum-free interval.
3.Secondary Outcome
Title Percentage of Participants With Best Overall Confirmed Objective Response of Complete Response (CR) or Partial Response (PR) Per Modified RECIST (Data Cutoff 14 November 2011)
Hide Description Objective Response was determined by the investigator using modified RECIST criteria, Version 1.0. An objective response was a complete or partial overall confirmed response as determined by investigators. CR defined as complete disappearance of all target and non-target lesions and no new lesions. PR defined as greater than or equal to (≥) 30 percent (%) decrease in the sum of appropriate diameters of all target measurable lesions, no progress in the non-measurable disease, and no new lesions. 95% CI computed using the normal approximation to the binomial distribution.
Time Frame Screening Visit, Every 8 weeks (or 9 weeks if receiving topotecan) until progression reported between day of first participant randomized (29 October 2009) until cutoff date of 14 November 2011
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population; only participants with measurable disease at baseline were included in the analysis.
Arm/Group Title Chemotherapy Chemotherapy + Bevacizumab
Hide Arm/Group Description:
Participants received one of the following chemotherapies at the discretion of the investigator: paclitaxel, 80 mg/m^2 as a 1-hour IV infusion on Days 1, 8, 15, and 22 q4w OR topotecan 4 mg/m^2 as a 30-minute IV infusion on Days 1, 8, and 15 q4w (alternatively, a 1.25 mg/m^2 dose could have been administered over 30 minutes on Days 1-5 q3w) OR PLD 40 mg/m^2 as a 1 mg/min infusion on Day 1 q4w (after Cycle 1 the drug could have been administered as a 1 hour infusion). Depending on chosen chemotherapy, pre-medication was implemented according to local practices.
Participants received one of the following chemotherapies at the discretion of the investigator: paclitaxel, 80 mg/m^2 as a 1-hour IV infusion on Days 1, 8, 15, and 22 q4w OR topotecan 4 mg/m^2 as a 30-minute IV infusion on Days 1, 8, and 15 q4w (alternatively, a 1.25 mg/m^2 dose could have been administered over 30 minutes on Days 1-5 q3w) OR PLD 40 mg/m^2 as a 1 mg/min infusion on Day 1 q4w (after Cycle 1 the drug could have been administered as a 1 hour infusion). Depending on chosen chemotherapy, pre-medication was implemented according to local practices. The chosen chemotherapy was combined with bevacizumab 10 mg/kg IV q2w (or bevacizumab 15 mg/kg q3w if used in combination with topotecan 1.25 mg/m^2 on Days 1-5 on a q3w schedule). The initial bevacizumab infusion was over 90 minutes, with subsequent infusions over 60 minutes and then 30 minutes, as tolerated.
Overall Number of Participants Analyzed 144 142
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
12.5
(7.1 to 17.9)
28.2
(20.8 to 35.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Chemotherapy, Chemotherapy + Bevacizumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Response Rates
Estimated Value 15.7
Confidence Interval (2-Sided) 95%
6.5 to 24.8
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Chemotherapy, Chemotherapy + Bevacizumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0010
Comments [Not Specified]
Method Pearson's chi-square
Comments unstratified analysis
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Chemotherapy, Chemotherapy + Bevacizumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0007
Comments Stratified analysis: The strata were chemotherapy selected (paclitaxel, PLD, or topotecan), prior anti-angiogenic therapy (yes or no), and platinum-free interval (<3 or 3-6 months).
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
4.Secondary Outcome
Title Duration of Objective Response (Data Cutoff 14 November 2011)
Hide Description For randomized participants who achieved an objective response per modified RECIST, duration of objective response was defined as the time from the date of the first occurrence of a CR or PR (whichever occurred first) until the date that progressive disease or death was documented (whichever occurred first). Participants who had an objective response and did not experience disease progression or death by the time of analysis were censored at the time of the last tumor assessment. Summaries of duration of objective response (median and percentiles) were estimated from Kaplan−Meier curves. 95% CI for duration of objective response was computed using the method of Brookmeyer and Crowley.
Time Frame Screening Visit, Every 8 weeks (or 9 weeks if receiving topotecan) until progression reported between day of first participant randomized (29 October 2009) until cutoff date of 14 November 2011
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population; only participants with a best overall confirmed response of CR or PR were included in the analysis.
Arm/Group Title Chemotherapy Chemotherapy + Bevacizumab
Hide Arm/Group Description:
Participants received one of the following chemotherapies at the discretion of the investigator: paclitaxel, 80 mg/m^2 as a 1-hour IV infusion on Days 1, 8, 15, and 22 q4w OR topotecan 4 mg/m^2 as a 30-minute IV infusion on Days 1, 8, and 15 q4w (alternatively, a 1.25 mg/m^2 dose could have been administered over 30 minutes on Days 1-5 q3w) OR PLD 40 mg/m^2 as a 1 mg/min infusion on Day 1 q4w (after Cycle 1 the drug could have been administered as a 1 hour infusion). Depending on chosen chemotherapy, pre-medication was implemented according to local practices.
Participants received one of the following chemotherapies at the discretion of the investigator: paclitaxel, 80 mg/m^2 as a 1-hour IV infusion on Days 1, 8, 15, and 22 q4w OR topotecan 4 mg/m^2 as a 30-minute IV infusion on Days 1, 8, and 15 q4w (alternatively, a 1.25 mg/m^2 dose could have been administered over 30 minutes on Days 1-5 q3w) OR PLD 40 mg/m^2 as a 1 mg/min infusion on Day 1 q4w (after Cycle 1 the drug could have been administered as a 1 hour infusion). Depending on chosen chemotherapy, pre-medication was implemented according to local practices. The chosen chemotherapy was combined with bevacizumab 10 mg/kg IV q2w (or bevacizumab 15 mg/kg q3w if used in combination with topotecan 1.25 mg/m^2 on Days 1-5 on a q3w schedule). The initial bevacizumab infusion was over 90 minutes, with subsequent infusions over 60 minutes and then 30 minutes, as tolerated.
Overall Number of Participants Analyzed 18 40
Median (95% Confidence Interval)
Unit of Measure: months
5.4
(3.81 to 9.23)
9.4
(6.60 to 11.63)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Chemotherapy, Chemotherapy + Bevacizumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0202
Comments Unstratified analysis
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.450
Confidence Interval (2-Sided) 95%
0.225 to 0.900
Estimation Comments Hazard ratio was estimated by unstratified Cox regression model.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Chemotherapy, Chemotherapy + Bevacizumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0081
Comments [Not Specified]
Method Peto-Peto-Prentice
Comments [Not Specified]
5.Secondary Outcome
Title Percentage of Participants Who Died (Data Cutoff 25 January 2013)
Hide Description [Not Specified]
Time Frame Screening Visit, Every 8 weeks (or 9 weeks if receiving topotecan) until progression reported between day of first participant randomized (29 October 2009) until cutoff date of 25 January 2013
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Chemotherapy Chemotherapy + Bevacizumab
Hide Arm/Group Description:
Participants received one of the following chemotherapies at the discretion of the investigator: paclitaxel, 80 mg/m^2 as a 1-hour IV infusion on Days 1, 8, 15, and 22 q4w OR topotecan 4 mg/m^2 as a 30-minute IV infusion on Days 1, 8, and 15 q4w (alternatively, a 1.25 mg/m^2 dose could have been administered over 30 minutes on Days 1-5 q3w) OR PLD 40 mg/m^2 as a 1 mg/min infusion on Day 1 q4w (after Cycle 1 the drug could have been administered as a 1 hour infusion). Depending on chosen chemotherapy, pre-medication was implemented according to local practices.
Participants received one of the following chemotherapies at the discretion of the investigator: paclitaxel, 80 mg/m^2 as a 1-hour IV infusion on Days 1, 8, 15, and 22 q4w OR topotecan 4 mg/m^2 as a 30-minute IV infusion on Days 1, 8, and 15 q4w (alternatively, a 1.25 mg/m^2 dose could have been administered over 30 minutes on Days 1-5 q3w) OR PLD 40 mg/m^2 as a 1 mg/min infusion on Day 1 q4w (after Cycle 1 the drug could have been administered as a 1 hour infusion). Depending on chosen chemotherapy, pre-medication was implemented according to local practices. The chosen chemotherapy was combined with bevacizumab 10 mg/kg IV q2w (or bevacizumab 15 mg/kg q3w if used in combination with topotecan 1.25 mg/m^2 on Days 1-5 on a q3w schedule). The initial bevacizumab infusion was over 90 minutes, with subsequent infusions over 60 minutes and then 30 minutes, as tolerated.
Overall Number of Participants Analyzed 182 179
Measure Type: Number
Unit of Measure: percentage of participants
75.8 71.5
6.Secondary Outcome
Title Overall Survival (Data Cutoff 25 January 2013)
Hide Description Duration of overall survival was defined as the time from randomization to death of any cause. Kaplan-Meier methodology was used. The OS data for participants for whom no death was captured in the clinical database were censored at the last time they were known to be alive. 95% CI was computed using the method of Brookmeyer and Crowley.
Time Frame Screening Visit, Every 8 weeks (or 9 weeks if receiving topotecan) until progression reported between day of first participant randomized (29 October 2009) until cutoff date of 25 January 2013
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population; only participants who died were included in the analysis.
Arm/Group Title Chemotherapy Chemotherapy + Bevacizumab
Hide Arm/Group Description:
Participants received one of the following chemotherapies at the discretion of the investigator: paclitaxel, 80 mg/m^2 as a 1-hour IV infusion on Days 1, 8, 15, and 22 q4w OR topotecan 4 mg/m^2 as a 30-minute IV infusion on Days 1, 8, and 15 q4w (alternatively, a 1.25 mg/m^2 dose could have been administered over 30 minutes on Days 1-5 q3w) OR PLD 40 mg/m^2 as a 1 mg/min infusion on Day 1 q4w (after Cycle 1 the drug could have been administered as a 1 hour infusion). Depending on chosen chemotherapy, pre-medication was implemented according to local practices.
Participants received one of the following chemotherapies at the discretion of the investigator: paclitaxel, 80 mg/m^2 as a 1-hour IV infusion on Days 1, 8, 15, and 22 q4w OR topotecan 4 mg/m^2 as a 30-minute IV infusion on Days 1, 8, and 15 q4w (alternatively, a 1.25 mg/m^2 dose could have been administered over 30 minutes on Days 1-5 q3w) OR PLD 40 mg/m^2 as a 1 mg/min infusion on Day 1 q4w (after Cycle 1 the drug could have been administered as a 1 hour infusion). Depending on chosen chemotherapy, pre-medication was implemented according to local practices. The chosen chemotherapy was combined with bevacizumab 10 mg/kg IV q2w (or bevacizumab 15 mg/kg q3w if used in combination with topotecan 1.25 mg/m^2 on Days 1-5 on a q3w schedule). The initial bevacizumab infusion was over 90 minutes, with subsequent infusions over 60 minutes and then 30 minutes, as tolerated.
Overall Number of Participants Analyzed 138 128
Median (95% Confidence Interval)
Unit of Measure: months
13.3
(11.89 to 16.43)
16.6
(13.70 to 18.99)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Chemotherapy, Chemotherapy + Bevacizumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1360
Comments Unstratified analysis
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.833
Confidence Interval (2-Sided) 95%
0.655 to 1.059
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Chemotherapy, Chemotherapy + Bevacizumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0715
Comments Unstratified analysis
Method Peto-Peto-Prentice
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Chemotherapy, Chemotherapy + Bevacizumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2711
Comments Stratified analysis: The strata were chemotherapy selected (paclitaxel, PLD, or topotecan), prior anti-angiogenic therapy (yes or no), and platinum-free interval (<3 or 3-6 months).
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.870
Confidence Interval (2-Sided) 95%
0.678 to 1.116
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Chemotherapy, Chemotherapy + Bevacizumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0890
Comments Stratified analysis: The strata were chemotherapy selected (paclitaxel, PLD, or topotecan), prior anti-angiogenic therapy (yes or no), and platinum-free interval (<3 or 3-6 months).
Method Peto-Peto-Prentice
Comments [Not Specified]
7.Secondary Outcome
Title European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) Ovarian (OV) 28 Abdominal/Gastrointestinal (AB/GI) Symptom Scale - Percentage of Responders (Data Cutoff 14 November 2011)
Hide Description The EORTC OV-28 module is a questionnaire that focuses on issues specific to ovarian cancer. It assesses AB/GI symptoms, among others. Participants were asked to indicate the extent to which they experienced AB/GI symptoms in the week prior to assessment. Participants responded on a scale of 1-4 (1=not at all, 2=a little, 3=quite a bit, 4=very much) to the following: Did you have abdominal pain? Did you have a bloated feeling in your abdomen/stomach? Did you have problems with your clothes feeling too tight? Did you experience any change in bowel habit as a result of your disease or treatment? Were you troubled by passing wind/gas/flatulence? Have you felt full too quickly after beginning to eat? Have you had indigestion/heartburn? Data are transformed to a scale from 0 to 100. Lower scores represent better health (fewer symptoms). Participants were considered a responder if they had a 10 point or more reduction in EORTC QLQ-OV28 AB/GI symptom scale score from baseline.
Time Frame Baseline and Weeks 8, 9, 16, 18, 24 and 30 (Data Cutoff 14 November 2011)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population; n (number) = (equals) number of participants that completed the questionnaire at baseline and at the specified visit.
Arm/Group Title Chemotherapy Chemotherapy + Bevacizumab
Hide Arm/Group Description:
Participants received one of the following chemotherapies at the discretion of the investigator: paclitaxel, 80 mg/m^2 as a 1-hour IV infusion on Days 1, 8, 15, and 22 q4w OR topotecan 4 mg/m^2 as a 30-minute IV infusion on Days 1, 8, and 15 q4w (alternatively, a 1.25 mg/m^2 dose could have been administered over 30 minutes on Days 1-5 q3w) OR PLD 40 mg/m^2 as a 1 mg/min infusion on Day 1 q4w (after Cycle 1 the drug could have been administered as a 1 hour infusion). Depending on chosen chemotherapy, pre-medication was implemented according to local practices.
Participants received one of the following chemotherapies at the discretion of the investigator: paclitaxel, 80 mg/m^2 as a 1-hour IV infusion on Days 1, 8, 15, and 22 q4w OR topotecan 4 mg/m^2 as a 30-minute IV infusion on Days 1, 8, and 15 q4w (alternatively, a 1.25 mg/m^2 dose could have been administered over 30 minutes on Days 1-5 q3w) OR PLD 40 mg/m^2 as a 1 mg/min infusion on Day 1 q4w (after Cycle 1 the drug could have been administered as a 1 hour infusion). Depending on chosen chemotherapy, pre-medication was implemented according to local practices. The chosen chemotherapy was combined with bevacizumab 10 mg/kg IV q2w (or bevacizumab 15 mg/kg q3w if used in combination with topotecan 1.25 mg/m^2 on Days 1-5 on a q3w schedule). The initial bevacizumab infusion was over 90 minutes, with subsequent infusions over 60 minutes and then 30 minutes, as tolerated.
Overall Number of Participants Analyzed 84 122
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Weeks 8/9 (n=84,122)
19.0
(11.3 to 29.1)
27.9
(20.1 to 36.7)
Weeks 16/18 (n=43,86)
23.3
(11.8 to 38.6)
26.7
(17.8 to 37.4)
Week 24 (n=22,53)
22.7
(7.8 to 45.4)
32.1
(19.9 to 46.3)
Week 30 (n=12,42)
33.3
(9.9 to 65.1)
28.6
(15.7 to 44.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Chemotherapy, Chemotherapy + Bevacizumab
Comments Comparison of responders at baseline versus Week 8/9
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1859
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Response Rates
Estimated Value 8.8
Confidence Interval (2-Sided) 95%
-3.8 to 21.4
Estimation Comments 95% CI was approximated with Hauck-Anderson continuity correction.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Chemotherapy, Chemotherapy + Bevacizumab
Comments Comparison of responders at baseline versus at Week 16/18
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8309
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Response Rates
Estimated Value 3.5
Confidence Interval (2-Sided) 95%
-14 to 20.9
Estimation Comments 95% CI was approximated with Hauck-Anderson continuity correction.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Chemotherapy, Chemotherapy + Bevacizumab
Comments Comparison of responders at baseline versus at Week 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5790
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Response Rates
Estimated Value 9.3
Confidence Interval (2-Sided) 95%
-15 to 34.1
Estimation Comments 95% CI was approximated with Hauck-Anderson continuity correction.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Chemotherapy, Chemotherapy + Bevacizumab
Comments Comparison of responders at baseline versus at Week 30
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7339
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Response Rates
Estimated Value -4.8
Confidence Interval (2-Sided) 95%
-40 to 30.6
Estimation Comments 95% CI was approximated with Hauck-Anderson continuity correction.
Time Frame Safety population was monitored for Adverse Events (AEs). AEs were recorded at every treatment visit and all follow-up visits until 2 months after the final follow-up visit.
Adverse Event Reporting Description Only Grade 2-5 AEs according to National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) were recorded per the protocol. One participant randomized to chemotherapy treatment received bevacizumab in error and 1 participant randomized to the chemotherapy + bevacizumab arm did not receive any protocol treatment.
 
Arm/Group Title Chemotherapy Chemotherapy + Bevacizumab
Hide Arm/Group Description Participants received one of the following chemotherapies at the discretion of the investigator: paclitaxel, 80 mg/m^2 as a 1-hour IV infusion on Days 1, 8, 15, and 22 q4w OR topotecan 4 mg/m^2 as a 30-minute IV infusion on Days 1, 8, and 15 q4w (alternatively, a 1.25 mg/m^2 dose could have been administered over 30 minutes on Days 1-5 q3w) OR PLD 40 mg/m^2 as a 1 mg/min infusion on Day 1 q4w (after Cycle 1 the drug could have been administered as a 1 hour infusion). Depending on chosen chemotherapy, pre-medication was implemented according to local practices. Participants received one of the following chemotherapies at the discretion of the investigator: paclitaxel, 80 mg/m^2 as a 1-hour IV infusion on Days 1, 8, 15, and 22 q4w OR topotecan 4 mg/m^2 as a 30-minute IV infusion on Days 1, 8, and 15 q4w (alternatively, a 1.25 mg/m^2 dose could have been administered over 30 minutes on Days 1-5 q3w) OR PLD 40 mg/m^2 as a 1 mg/min infusion on Day 1 q4w (after Cycle 1 the drug could have been administered as a 1 hour infusion). Depending on chosen chemotherapy, pre-medication was implemented according to local practices. The chosen chemotherapy was combined with bevacizumab 10 mg/kg IV q2w (or bevacizumab 15 mg/kg q3w if used in combination with topotecan 1.25 mg/m^2 on Days 1-5 on a q3w schedule). The initial bevacizumab infusion was over 90 minutes, with subsequent infusions over 60 minutes and then 30 minutes, as tolerated.
All-Cause Mortality
Chemotherapy Chemotherapy + Bevacizumab
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Chemotherapy Chemotherapy + Bevacizumab
Affected / at Risk (%) Affected / at Risk (%)
Total   49/181 (27.07%)   56/179 (31.28%) 
Blood and lymphatic system disorders     
Neutropenia * 1  3/181 (1.66%)  1/179 (0.56%) 
Anaemia * 1  2/181 (1.10%)  0/179 (0.00%) 
Febrile neutropenia * 1  1/181 (0.55%)  0/179 (0.00%) 
Cardiac disorders     
Arrhythmia supraventricular * 1  1/181 (0.55%)  0/179 (0.00%) 
Atrial flutter * 1  1/181 (0.55%)  0/179 (0.00%) 
Cardiac arrest * 1  0/181 (0.00%)  1/179 (0.56%) 
Cardiac failure * 1  1/181 (0.55%)  0/179 (0.00%) 
Coronary artery disease * 1  0/181 (0.00%)  1/179 (0.56%) 
Coronary artery stenosis * 1  0/181 (0.00%)  1/179 (0.56%) 
Myocardial ischaemia * 1  0/181 (0.00%)  1/179 (0.56%) 
Gastrointestinal disorders     
Abdominal pain * 1  5/181 (2.76%)  4/179 (2.23%) 
Ileus * 1  2/181 (1.10%)  4/179 (2.23%) 
Subileus * 1  6/181 (3.31%)  4/179 (2.23%) 
Constipation * 1  2/181 (1.10%)  3/179 (1.68%) 
Small intestinal obstruction * 1  0/181 (0.00%)  2/179 (1.12%) 
Ascites * 1  3/181 (1.66%)  0/179 (0.00%) 
Diarrhoea * 1  2/181 (1.10%)  0/179 (0.00%) 
Vomiting * 1  7/181 (3.87%)  0/179 (0.00%) 
Abdominal pain upper * 1  0/181 (0.00%)  1/179 (0.56%) 
Gastrointestinal haemorrhage * 1  1/181 (0.55%)  1/179 (0.56%) 
Gastrointestinal hypomotility * 1  1/181 (0.55%)  0/179 (0.00%) 
Haemorrhagic ascites * 1  0/181 (0.00%)  1/179 (0.56%) 
Ileal perforation * 1  0/181 (0.00%)  1/179 (0.56%) 
Ileal stenosis * 1  0/181 (0.00%)  1/179 (0.56%) 
Intestinal obstruction * 1  1/181 (0.55%)  1/179 (0.56%) 
Intestinal perforation * 1  0/181 (0.00%)  1/179 (0.56%) 
Nausea * 1  1/181 (0.55%)  0/179 (0.00%) 
General disorders     
General physical health deterioration * 1  1/181 (0.55%)  3/179 (1.68%) 
Pyrexia * 1  3/181 (1.66%)  3/179 (1.68%) 
Fatigue * 1  2/181 (1.10%)  0/179 (0.00%) 
Catheter site necrosis * 1  0/181 (0.00%)  1/179 (0.56%) 
General symptom * 1  1/181 (0.55%)  0/179 (0.00%) 
Influenza like illness * 1  0/181 (0.00%)  1/179 (0.56%) 
Multi-organ failure * 1  1/181 (0.55%)  0/179 (0.00%) 
Hepatobiliary disorders     
Cholestasis * 1  1/181 (0.55%)  0/179 (0.00%) 
Hypertransaminasaemia * 1  0/181 (0.00%)  1/179 (0.56%) 
Immune system disorders     
Food allergy * 1  1/181 (0.55%)  0/179 (0.00%) 
Infections and infestations     
Device related infection * 1  1/181 (0.55%)  2/179 (1.12%) 
Infection * 1  2/181 (1.10%)  1/179 (0.56%) 
Pneumonia * 1  2/181 (1.10%)  0/179 (0.00%) 
Bacteraemia * 1  0/181 (0.00%)  1/179 (0.56%) 
Cystitis * 1  1/181 (0.55%)  0/179 (0.00%) 
Gastroenteritis * 1  1/181 (0.55%)  1/179 (0.56%) 
Gastroenteritis viral * 1  1/181 (0.55%)  0/179 (0.00%) 
Infectious peritonitis * 1  0/181 (0.00%)  1/179 (0.56%) 
Peritonitis * 1  1/181 (0.55%)  0/179 (0.00%) 
Postoperative wound infection * 1  0/181 (0.00%)  1/179 (0.56%) 
Sepsis * 1  1/181 (0.55%)  1/179 (0.56%) 
Septic shock * 1  1/181 (0.55%)  0/179 (0.00%) 
Tooth abscess * 1  0/181 (0.00%)  1/179 (0.56%) 
Injury, poisoning and procedural complications     
Wrong drug administered * 1  0/181 (0.00%)  1/179 (0.56%) 
Metabolism and nutrition disorders     
Dehydration * 1  1/181 (0.55%)  2/179 (1.12%) 
Decreased appetite * 1  0/181 (0.00%)  1/179 (0.56%) 
Musculoskeletal and connective tissue disorders     
Bone disorder * 1  0/181 (0.00%)  1/179 (0.56%) 
Bone pain * 1  0/181 (0.00%)  1/179 (0.56%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Breast cancer * 1  0/181 (0.00%)  1/179 (0.56%) 
Nervous system disorders     
Depressed level of consciousness * 1  1/181 (0.55%)  0/179 (0.00%) 
Ischaemic stroke * 1  0/181 (0.00%)  1/179 (0.56%) 
Posterior reversible encephalopathy syndrome * 1  0/181 (0.00%)  1/179 (0.56%) 
Sciatica * 1  1/181 (0.55%)  0/179 (0.00%) 
Syncope * 1  0/181 (0.00%)  1/179 (0.56%) 
Renal and urinary disorders     
Vesical fistula * 1  0/181 (0.00%)  2/179 (1.12%) 
Hydronephrosis * 1  1/181 (0.55%)  0/179 (0.00%) 
Nephrotic syndrome * 1  0/181 (0.00%)  1/179 (0.56%) 
Renal failure * 1  1/181 (0.55%)  0/179 (0.00%) 
Reproductive system and breast disorders     
Female genital tract fistula * 1  0/181 (0.00%)  2/179 (1.12%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea * 1  5/181 (2.76%)  4/179 (2.23%) 
Pleural effusion * 1  1/181 (0.55%)  2/179 (1.12%) 
Pneumonia aspiration * 1  0/181 (0.00%)  2/179 (1.12%) 
Pulmonary embolism * 1  5/181 (2.76%)  2/179 (1.12%) 
Skin and subcutaneous tissue disorders     
Skin ulcer * 1  0/181 (0.00%)  1/179 (0.56%) 
Surgical and medical procedures     
Cytoreductive surgery * 1  1/181 (0.55%)  0/179 (0.00%) 
Vascular disorders     
Hypertension * 1  0/181 (0.00%)  4/179 (2.23%) 
Arterial occlusive disease * 1  0/181 (0.00%)  1/179 (0.56%) 
Deep vein thrombosis * 1  0/181 (0.00%)  1/179 (0.56%) 
Embolism arterial * 1  0/181 (0.00%)  1/179 (0.56%) 
Embolism venous * 1  1/181 (0.55%)  1/179 (0.56%) 
Hypertensive crisis * 1  0/181 (0.00%)  1/179 (0.56%) 
Shock * 1  0/181 (0.00%)  1/179 (0.56%) 
Venous thrombosis * 1  0/181 (0.00%)  1/179 (0.56%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, NCTCAE, Version 3.0,
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Chemotherapy Chemotherapy + Bevacizumab
Affected / at Risk (%) Affected / at Risk (%)
Total   140/181 (77.35%)   146/179 (81.56%) 
Blood and lymphatic system disorders     
Anaemia * 1  45/181 (24.86%)  36/179 (20.11%) 
Leukopenia * 1  25/181 (13.81%)  23/179 (12.85%) 
Neutropenia * 1  44/181 (24.31%)  54/179 (30.17%) 
Thrombocytopenia * 1  12/181 (6.63%)  10/179 (5.59%) 
Gastrointestinal disorders     
Abdominal pain * 1  21/181 (11.60%)  16/179 (8.94%) 
Abdominal pain upper * 1  6/181 (3.31%)  9/179 (5.03%) 
Constipation * 1  17/181 (9.39%)  13/179 (7.26%) 
Diarrhoea * 1  11/181 (6.08%)  17/179 (9.50%) 
Nausea * 1  15/181 (8.29%)  18/179 (10.06%) 
Vomiting * 1  17/181 (9.39%)  14/179 (7.82%) 
General disorders     
Fatigue * 1  51/181 (28.18%)  50/179 (27.93%) 
Mucosal inflammation * 1  11/181 (6.08%)  23/179 (12.85%) 
Infections and infestations     
Infection * 1  7/181 (3.87%)  18/179 (10.06%) 
Urinary tract infection * 1  17/181 (9.39%)  15/179 (8.38%) 
Investigations     
Weight decreased * 1  6/181 (3.31%)  11/179 (6.15%) 
Metabolism and nutrition disorders     
Decreased appetite * 1  14/181 (7.73%)  10/179 (5.59%) 
Nervous system disorders     
Peripheral sensory neuropathy * 1  16/181 (8.84%)  32/179 (17.88%) 
Renal and urinary disorders     
Proteinuria * 1  3/181 (1.66%)  22/179 (12.29%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea * 1  5/181 (2.76%)  10/179 (5.59%) 
Epistaxis * 1  0/181 (0.00%)  9/179 (5.03%) 
Skin and subcutaneous tissue disorders     
Alopecia * 1  11/181 (6.08%)  16/179 (8.94%) 
Palmar-plantar erythrodysaesthesia syndrome * 1  11/181 (6.08%)  19/179 (10.61%) 
Vascular disorders     
Hypertension * 1  18/181 (9.94%)  30/179 (16.76%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, NCTCAE, Version 3.0,
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 after the first publication or presentation that involves the overall study. 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
Layout table for Results Point of Contact information
Name/Title: Medical Communications
Organization: Hoffmann- LaRoche
Phone: 1-800-821-8590
EMail: genentech@druginfo.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00976911     History of Changes
Other Study ID Numbers: MO22224
2009-011400-33
First Submitted: September 14, 2009
First Posted: September 15, 2009
Results First Submitted: December 3, 2014
Results First Posted: February 25, 2015
Last Update Posted: February 25, 2015