Trial Outcomes & Findings for A Study of Bevacizumab in Combination With Gemcitabine and Carboplatin in Participants With Triple Negative Metastatic Breast Cancer (NCT NCT01201265)
NCT ID: NCT01201265
Last Updated: 2016-05-27
Results Overview
Progression free survival (PFS) was calculated in days from the date of registration until the earliest date of documented disease progression or death. The median PFS time with 95% confidence interval (CI) was estimated using Kaplan Meier method. The progression-free survival was assessed utilizing computer tomography (CT)/ magnetic resonance imaging (MRI)/bone scans and X-ray and Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1. Progression of disease is defined as at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions.
COMPLETED
PHASE2
40 participants
From the date of registration until the disease progression or death (up to 1541 days).
2016-05-27
Participant Flow
Participant milestones
| Measure |
All Participants
Participants received a combination therapy of bevacizumab 15 milligram per kilogram (mg/kg) intravenous every 3 weeks with carboplatin recommended dose (area under curve \[AUC\]= 2) along with gemcitabine 1000 mg/ metre square (m\^2) on days 1 and 8 of each 3 week cycle.
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|---|---|
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Overall Study
STARTED
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40
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Overall Study
COMPLETED
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2
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Overall Study
NOT COMPLETED
|
38
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Reasons for withdrawal
| Measure |
All Participants
Participants received a combination therapy of bevacizumab 15 milligram per kilogram (mg/kg) intravenous every 3 weeks with carboplatin recommended dose (area under curve \[AUC\]= 2) along with gemcitabine 1000 mg/ metre square (m\^2) on days 1 and 8 of each 3 week cycle.
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|---|---|
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Overall Study
Death
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14
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Overall Study
Insufficient Therapeutic Response
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3
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Overall Study
Lost to Follow-up
|
10
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Overall Study
Withdrawal by Subject
|
7
|
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Overall Study
Disease Progression
|
4
|
Baseline Characteristics
A Study of Bevacizumab in Combination With Gemcitabine and Carboplatin in Participants With Triple Negative Metastatic Breast Cancer
Baseline characteristics by cohort
| Measure |
All Participants
n=40 Participants
Participants received a combination therapy of bevacizumab 15 milligram per kilogram (mg/kg) intravenous every 3 weeks with carboplatin recommended dose (area under curve \[AUC\]= 2) along with gemcitabine 1000 mg/ metre square (m\^2) on days 1 and 8 of each 3 week cycle.
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|---|---|
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Age, Continuous
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47.5 years
STANDARD_DEVIATION 10.68 • n=93 Participants
|
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Sex: Female, Male
Female
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40 Participants
n=93 Participants
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Sex: Female, Male
Male
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0 Participants
n=93 Participants
|
PRIMARY outcome
Timeframe: From the date of registration until the disease progression or death (up to 1541 days).Population: Efficacy analysis population included all participants who received at least one dose of study treatment and with at least one efficacy assessment
Progression free survival (PFS) was calculated in days from the date of registration until the earliest date of documented disease progression or death. The median PFS time with 95% confidence interval (CI) was estimated using Kaplan Meier method. The progression-free survival was assessed utilizing computer tomography (CT)/ magnetic resonance imaging (MRI)/bone scans and X-ray and Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1. Progression of disease is defined as at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions.
Outcome measures
| Measure |
All Participants
n=40 Participants
Participants received a combination therapy of bevacizumab 15 milligram per kilogram (mg/kg) intravenous every 3 weeks with carboplatin recommended dose (area under curve \[AUC\]= 2) along with gemcitabine 1000 mg/ metre square (m\^2) on days 1 and 8 of each 3 week cycle.
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|---|---|
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Progression-free Survival (PFS)
|
255 days
Interval 157.0 to 465.0
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SECONDARY outcome
Timeframe: From the date of registration until the disease progression or death (up to 1541 days)Population: Efficacy analysis population included all participants who received at least one dose of study treatment and with at least one efficacy assessment.
The overall response rate (ORR) was defined as complete response (CR) + partial response (PR). ORR was summarized using number and percentage along with two-sided 95% Pearson-Clopper CI. The overall response rate was assessed utilizing the RECIST v. 1.1. CR: disappearance of all target and non-target lesions (TLs) and normalization of tumor markers. Pathological lymph nodes must have short axis measures less than (\<) 10 millimeter (mm). PR: at least a 30% decrease in the sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of TLs, taking as reference the baseline sum of diameters.
Outcome measures
| Measure |
All Participants
n=40 Participants
Participants received a combination therapy of bevacizumab 15 milligram per kilogram (mg/kg) intravenous every 3 weeks with carboplatin recommended dose (area under curve \[AUC\]= 2) along with gemcitabine 1000 mg/ metre square (m\^2) on days 1 and 8 of each 3 week cycle.
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|---|---|
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Percentage of Participants Achieving an Overall Response
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50.0 percentage of participants
Interval 33.8 to 66.2
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SECONDARY outcome
Timeframe: From the date of registration until the disease progression or death (up to 1541 days)Population: Efficacy analysis population included all participants who received at least one dose of study treatment and with at least one efficacy assessment.
Clinical benefit response was defined as a complete response (CR), partial response (PR) or stable disease (SD). CBR was assessed using Recist v.1.1. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Outcome measures
| Measure |
All Participants
n=40 Participants
Participants received a combination therapy of bevacizumab 15 milligram per kilogram (mg/kg) intravenous every 3 weeks with carboplatin recommended dose (area under curve \[AUC\]= 2) along with gemcitabine 1000 mg/ metre square (m\^2) on days 1 and 8 of each 3 week cycle.
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|---|---|
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Percentage of Participants Achieving a Clinical Benefit Response (CBR)
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92.5 percentage of participants
Interval 79.6 to 98.4
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SECONDARY outcome
Timeframe: From the date of registration until the disease progression (up to 1541 days).Population: Efficacy analysis population included all participants who received at least one dose of study treatment and with at least one efficacy assessment.
Duration of time to progression (TTP) was estimated using the Kaplan-Meier method. The time to progression was calculated in days from the date of registration until the earliest date of documented disease progression.
Outcome measures
| Measure |
All Participants
n=40 Participants
Participants received a combination therapy of bevacizumab 15 milligram per kilogram (mg/kg) intravenous every 3 weeks with carboplatin recommended dose (area under curve \[AUC\]= 2) along with gemcitabine 1000 mg/ metre square (m\^2) on days 1 and 8 of each 3 week cycle.
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|---|---|
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Time to Progression (TTP)
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269.0 days
Interval 182.0 to 551.0
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SECONDARY outcome
Timeframe: From the date of registration until the disease progression or death (up to 1541 days)Population: Efficacy analysis population included all participants who received at least one dose of study treatment and with at least one efficacy assessment.
Overall survival was measured from the date of the first study drug dose to the date of death from any cause. The median overall survival time with 95%CI was estimated using Kaplan-Meier method.
Outcome measures
| Measure |
All Participants
n=40 Participants
Participants received a combination therapy of bevacizumab 15 milligram per kilogram (mg/kg) intravenous every 3 weeks with carboplatin recommended dose (area under curve \[AUC\]= 2) along with gemcitabine 1000 mg/ metre square (m\^2) on days 1 and 8 of each 3 week cycle.
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|---|---|
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Overall Survival (OS)
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475.0 days
Interval 358.0 to 759.0
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SECONDARY outcome
Timeframe: Up to 28 days after termination of study treatment (approximately 1569 days)Population: Safety population included all participants who received at least one dose of study treatment.
An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Outcome measures
| Measure |
All Participants
n=40 Participants
Participants received a combination therapy of bevacizumab 15 milligram per kilogram (mg/kg) intravenous every 3 weeks with carboplatin recommended dose (area under curve \[AUC\]= 2) along with gemcitabine 1000 mg/ metre square (m\^2) on days 1 and 8 of each 3 week cycle.
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|---|---|
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Number of Participants With an Adverse Event (AE)
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24 participants
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SECONDARY outcome
Timeframe: Baseline, cycle 6Population: Efficacy analysis population included all participants who received at least one dose of study treatment and with at least one efficacy assessment. Here, n signifies the number of participants evaluable at specified time points.
The EORTC QLQ-C30 (version 3.0) questionnaire incorporates 9 multi scale items: 5 functional scales (physical, role, cognitive, emotional and social); 3 symptom scales (fatigue, pain and nausea \& vomiting); and a global health and quality-of-life scale. It contains 30 questions. The score for each item and the overall score ranges from 0 to 100. A high overall scale and subscale scores represent improved health status. However, in case of symptoms, higher scores suggest increased perception of these symptoms.
Outcome measures
| Measure |
All Participants
n=40 Participants
Participants received a combination therapy of bevacizumab 15 milligram per kilogram (mg/kg) intravenous every 3 weeks with carboplatin recommended dose (area under curve \[AUC\]= 2) along with gemcitabine 1000 mg/ metre square (m\^2) on days 1 and 8 of each 3 week cycle.
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|---|---|
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Change From Baseline to Cycle 6 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-30)
Baseline; physical (n=40)
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69.33 units on a scale
Standard Deviation 20.963
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Change From Baseline to Cycle 6 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-30)
Change at Cycle 6; physical (n=28)
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-8.82 units on a scale
Standard Deviation 24.154
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Change From Baseline to Cycle 6 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-30)
Baseline; role (n=40)
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71.26 units on a scale
Standard Deviation 25.311
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Change From Baseline to Cycle 6 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-30)
Change at Cycle 6; role (n=28)
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-5.36 units on a scale
Standard Deviation 22.705
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Change From Baseline to Cycle 6 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-30)
Baseline; cognitive (n=40)
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74.58 units on a scale
Standard Deviation 24.745
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Change From Baseline to Cycle 6 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-30)
Change at Cycle 6; cognitive (n=28)
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-4.17 units on a scale
Standard Deviation 27.444
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Change From Baseline to Cycle 6 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-30)
Baseline; emotional (n=40)
|
61.87 units on a scale
Standard Deviation 22.396
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Change From Baseline to Cycle 6 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-30)
Change at Cycle 6; emotional (n=28)
|
-15.78 units on a scale
Standard Deviation 23.929
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Change From Baseline to Cycle 6 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-30)
Baseline; social (n=40)
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65.42 units on a scale
Standard Deviation 29.330
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Change From Baseline to Cycle 6 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-30)
Change at Cycle 6; social (n=28)
|
-8.33 units on a scale
Standard Deviation 27.026
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Change From Baseline to Cycle 6 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-30)
Baseline; fatigue (n=40)
|
42.21 units on a scale
Standard Deviation 20.026
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Change From Baseline to Cycle 6 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-30)
Change at Cycle 6; fatigue (n=28)
|
8.35 units on a scale
Standard Deviation 25.785
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Change From Baseline to Cycle 6 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-30)
Baseline; pain (n=40)
|
34.58 units on a scale
Standard Deviation 25.428
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Change From Baseline to Cycle 6 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-30)
Change at Cycle 6; pain (n=28)
|
13.09 units on a scale
Standard Deviation 33.744
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Change From Baseline to Cycle 6 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-30)
Baseline; nausea and vomiting (n=40)
|
16.67 units on a scale
Standard Deviation 20.326
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Change From Baseline to Cycle 6 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-30)
Change at Cycle 6; nausea and vomiting (n=28)
|
2.38 units on a scale
Standard Deviation 19.082
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Change From Baseline to Cycle 6 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-30)
Baseline; global health & QOL (n=40)
|
58.55 units on a scale
Standard Deviation 17.750
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Change From Baseline to Cycle 6 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-30)
Change at Cycle 6; global health & QOL (n=28)
|
-3.86 units on a scale
Standard Deviation 17.191
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SECONDARY outcome
Timeframe: Baseline, Cycle 6, 12 of treatmentPopulation: Safety population included all participants who received at least one dose of study treatment. Here, n signifies the number of participants evaluable at specified time points.
Change from baseline in SBP was analyzed by overall response (CR+PR, SD+PD).
Outcome measures
| Measure |
All Participants
n=40 Participants
Participants received a combination therapy of bevacizumab 15 milligram per kilogram (mg/kg) intravenous every 3 weeks with carboplatin recommended dose (area under curve \[AUC\]= 2) along with gemcitabine 1000 mg/ metre square (m\^2) on days 1 and 8 of each 3 week cycle.
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|---|---|
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Change From Baseline in Systolic Blood Pressure (SBP)
Baseline; CR+PR (n= 19)
|
124.8 millimetre of mercury (mmHg)
Standard Deviation 12.86
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Change From Baseline in Systolic Blood Pressure (SBP)
Change at cycle 6; CR+PR (n=14)
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-4.6 millimetre of mercury (mmHg)
Standard Deviation 12.16
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Change From Baseline in Systolic Blood Pressure (SBP)
Change at cycle 12; CR+PR at cycle 12 (n=5)
|
-4.0 millimetre of mercury (mmHg)
Standard Deviation 18.17
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Change From Baseline in Systolic Blood Pressure (SBP)
Baseline; SD+PD (n= 18)
|
123.6 millimetre of mercury (mmHg)
Standard Deviation 6.82
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Change From Baseline in Systolic Blood Pressure (SBP)
Change at cycle 6; SD+PD at cycle 6 (n=13)
|
0.2 millimetre of mercury (mmHg)
Standard Deviation 12.68
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Change From Baseline in Systolic Blood Pressure (SBP)
Change at cycle 12; SD+PD at cycle 12 (n=4)
|
-6.3 millimetre of mercury (mmHg)
Standard Deviation 17.97
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SECONDARY outcome
Timeframe: Baseline, Cycle 6, 12 of treatmentPopulation: Safety population included all participants who received at least one dose of study treatment. Here, n signifies the number of participants evaluable at specified time points.
Change from baseline in DBP was analyzed by overall response (CR+PR, SD+PD).
Outcome measures
| Measure |
All Participants
n=40 Participants
Participants received a combination therapy of bevacizumab 15 milligram per kilogram (mg/kg) intravenous every 3 weeks with carboplatin recommended dose (area under curve \[AUC\]= 2) along with gemcitabine 1000 mg/ metre square (m\^2) on days 1 and 8 of each 3 week cycle.
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|---|---|
|
Change From Baseline in Diastolic Blood Pressure (DBP)
Baseline; CR+PR (n= 19)
|
80.4 mmHg
Standard Deviation 9.65
|
|
Change From Baseline in Diastolic Blood Pressure (DBP)
Change at cycle 6; CR+PR (n=14)
|
-4.1 mmHg
Standard Deviation 10.83
|
|
Change From Baseline in Diastolic Blood Pressure (DBP)
Change at cycle 12; CR+PR (n=5)
|
-2.0 mmHg
Standard Deviation 14.83
|
|
Change From Baseline in Diastolic Blood Pressure (DBP)
Baseline; SD+PD (n= 18)
|
78.9 mmHg
Standard Deviation 7.58
|
|
Change From Baseline in Diastolic Blood Pressure (DBP)
Change at cycle 6; SD+PD (n=13)
|
2.3 mmHg
Standard Deviation 10.92
|
|
Change From Baseline in Diastolic Blood Pressure (DBP)
Change at cycle 12; SD+PD (n=4)
|
7.5 mmHg
Standard Deviation 12.58
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Adverse Events
All Particiapants
Serious adverse events
| Measure |
All Particiapants
n=40 participants at risk
Participants received a combination therapy of bevacizumab 15 milligram per kilogram (mg/kg) intravenous every 3 weeks with carboplatin recommended dose (area under curve \[AUC\]= 2) along with gemcitabine 1000 mg/ metre square (m\^2) on days 1 and 8 of each 3 week cycle.
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|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
5.0%
2/40 • Up to 28 days after termination of study treatment (approximately 1569 days)
|
|
Blood and lymphatic system disorders
Febrile Neutropenia
|
7.5%
3/40 • Up to 28 days after termination of study treatment (approximately 1569 days)
|
|
Blood and lymphatic system disorders
Neutropenia
|
5.0%
2/40 • Up to 28 days after termination of study treatment (approximately 1569 days)
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
12.5%
5/40 • Up to 28 days after termination of study treatment (approximately 1569 days)
|
|
Cardiac disorders
Pericardial Effusion
|
2.5%
1/40 • Up to 28 days after termination of study treatment (approximately 1569 days)
|
|
Gastrointestinal disorders
Abdominal Pain Lower
|
2.5%
1/40 • Up to 28 days after termination of study treatment (approximately 1569 days)
|
|
General disorders
Disease Progression
|
15.0%
6/40 • Up to 28 days after termination of study treatment (approximately 1569 days)
|
|
General disorders
Fatigue
|
2.5%
1/40 • Up to 28 days after termination of study treatment (approximately 1569 days)
|
|
General disorders
Pyrexia
|
7.5%
3/40 • Up to 28 days after termination of study treatment (approximately 1569 days)
|
|
Infections and infestations
Septic Shock
|
2.5%
1/40 • Up to 28 days after termination of study treatment (approximately 1569 days)
|
|
Infections and infestations
Streptococcal Infection
|
2.5%
1/40 • Up to 28 days after termination of study treatment (approximately 1569 days)
|
|
Infections and infestations
Viral Respiratory Tract Infection
|
2.5%
1/40 • Up to 28 days after termination of study treatment (approximately 1569 days)
|
|
Injury, poisoning and procedural complications
Contusion
|
2.5%
1/40 • Up to 28 days after termination of study treatment (approximately 1569 days)
|
|
Investigations
Oxygen Saturation Decreased
|
2.5%
1/40 • Up to 28 days after termination of study treatment (approximately 1569 days)
|
|
Nervous system disorders
Transient Ischemic Attack
|
2.5%
1/40 • Up to 28 days after termination of study treatment (approximately 1569 days)
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
2.5%
1/40 • Up to 28 days after termination of study treatment (approximately 1569 days)
|
|
Respiratory, thoracic and mediastinal disorders
Pleural Effusion
|
5.0%
2/40 • Up to 28 days after termination of study treatment (approximately 1569 days)
|
|
Vascular disorders
Deep Vein Thrombosis
|
2.5%
1/40 • Up to 28 days after termination of study treatment (approximately 1569 days)
|
Other adverse events
| Measure |
All Particiapants
n=40 participants at risk
Participants received a combination therapy of bevacizumab 15 milligram per kilogram (mg/kg) intravenous every 3 weeks with carboplatin recommended dose (area under curve \[AUC\]= 2) along with gemcitabine 1000 mg/ metre square (m\^2) on days 1 and 8 of each 3 week cycle.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
12.5%
5/40 • Up to 28 days after termination of study treatment (approximately 1569 days)
|
|
Blood and lymphatic system disorders
Febrile Neutropenia
|
5.0%
2/40 • Up to 28 days after termination of study treatment (approximately 1569 days)
|
|
Blood and lymphatic system disorders
Leukopenia
|
7.5%
3/40 • Up to 28 days after termination of study treatment (approximately 1569 days)
|
|
Blood and lymphatic system disorders
Neutropenia
|
25.0%
10/40 • Up to 28 days after termination of study treatment (approximately 1569 days)
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
22.5%
9/40 • Up to 28 days after termination of study treatment (approximately 1569 days)
|
|
Gastrointestinal disorders
Stomatitis
|
5.0%
2/40 • Up to 28 days after termination of study treatment (approximately 1569 days)
|
|
General disorders
Disease Progression
|
7.5%
3/40 • Up to 28 days after termination of study treatment (approximately 1569 days)
|
Additional Information
Medical Communications
Hoffmann-La Roche
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