Trial Outcomes & Findings for A Study of Carboplatin and Gemcitabine Plus Bevacizumab in Patients With Ovary, Peritoneal, or Fallopian Tube Carcinoma (NCT NCT00434642)

Last Updated: 2017-08-09

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

484 participants

Primary outcome timeframe

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

Results posted on

2017-08-09

Participant Flow

Participant milestones

Participant milestones
Measure	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.	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.
Blinded Treatment Phase STARTED	242	242
Blinded Treatment Phase COMPLETED	0	13
Blinded Treatment Phase NOT COMPLETED	242	229
Open-label Treatment Phase STARTED	0	12
Open-label Treatment Phase COMPLETED	0	1
Open-label Treatment Phase NOT COMPLETED	0	11

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.
Blinded Treatment Phase Adverse Event	12	58
Blinded Treatment Phase Clinical Disease Progression	4	5
Blinded Treatment Phase Disease Progression Per RECIST	168	109
Blinded Treatment Phase Physician Decision	19	27
Blinded Treatment Phase Sponsor's Decision To Terminate Study	3	0
Blinded Treatment Phase Subject's Decision-Discontinue Treatment	32	29
Blinded Treatment Phase Did not Receive Treatment	4	1
Open-label Treatment Phase Adverse Event	0	5
Open-label Treatment Phase Disease Progression Per RECIST	0	6

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Carboplatin and Gemcitabine + Placebo n=242 Participants 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 and Gemcitabine + Bevacizumab n=242 Participants 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 n=484 Participants Total of all reporting groups
Age, Continuous	61.6 years STANDARD_DEVIATION 10.2 • n=5 Participants	60.5 years STANDARD_DEVIATION 9.8 • n=7 Participants	61.0 years STANDARD_DEVIATION 10.0 • n=5 Participants
Sex: Female, Male Female	242 Participants n=5 Participants	242 Participants n=7 Participants	484 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

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

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

Outcome measures

Outcome measures
Measure	Carboplatin and Gemcitabine + Bevacizumab n=242 Participants 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 and Gemcitabine + Placebo n=242 Participants 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.
Progression Free Survival (PFS) as Determined by the Investigator, Per Response Evaluation Criteria for Solid Tumors (RECIST)	12.4 Months Interval 11.4 to 12.71	8.4 Months Interval 8.31 to 9.66

SECONDARY outcome

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

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

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.

Outcome measures

Outcome measures
Measure	Carboplatin and Gemcitabine + Bevacizumab n=242 Participants 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 and Gemcitabine + Placebo n=242 Participants 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.
Percentage of Patients With an Objective Response as Determined by the Investigator, Per Response Evaluation Criteria for Solid Tumors (RECIST)	78.5 Percentage of participants	57.4 Percentage of participants

SECONDARY outcome

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

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

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.

Outcome measures

Outcome measures
Measure	Carboplatin and Gemcitabine + Bevacizumab n=190 Participants 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 and Gemcitabine + Placebo n=139 Participants 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.
Duration of Objective Response (OR) as Determined by the Investigator, Per Response Evaluation Criteria for Solid Tumors (RECIST)	10.4 Months Interval 9.36 to 11.83	7.4 Months Interval 6.31 to 8.31

SECONDARY outcome

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

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

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

Outcome measures

Outcome measures
Measure	Carboplatin and Gemcitabine + Bevacizumab n=242 Participants 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 and Gemcitabine + Placebo n=242 Participants 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 Survival	33.6 Months Interval 30.32 to 35.84	32.9 Months Interval 29.8 to 37.68

SECONDARY outcome

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

Population: 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.

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

Outcome measures

Outcome measures
Measure	Carboplatin and Gemcitabine + Bevacizumab n=247 Participants 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 and Gemcitabine + Placebo n=233 Participants 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.
Percentage of Patients Who Had a Gastrointestinal Perforation (GIP)	0 Percentage of participants	0 Percentage of participants

SECONDARY outcome

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

Outcome measures

Outcome measures
Measure	Carboplatin and Gemcitabine + Bevacizumab n=247 Participants 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 and Gemcitabine + Placebo n=233 Participants 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.
Percentage of Patients Who Had at Least 1 Adverse Event	100.0 Percentage of participants	100.0 Percentage of participants

Adverse Events

Carboplatin and Gemcitabine + Bevacizumab

Serious events: 90 serious events

Other events: 246 other events

Deaths: 0 deaths

Carboplatin and Gemcitabine + Placebo

Serious events: 59 serious events

Other events: 233 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Communications

Hoffman-LaRoche

Phone: 800-821-8590

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER