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Trial record 24 of 173 for:    pertuzumab

A Study to Evaluate the Efficacy and Safety of Pertuzumab + Trastuzumab + Docetaxel Versus Placebo + Trastuzumab + Docetaxel in Previously Untreated Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Metastatic Breast Cancer (MBC)

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ClinicalTrials.gov Identifier: NCT02896855
Recruitment Status : Active, not recruiting
First Posted : September 12, 2016
Results First Posted : July 10, 2019
Last Update Posted : September 18, 2019
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Breast Cancer
Interventions Drug: Docetaxel
Drug: Pertuzumab
Drug: Placebo
Drug: Trastuzumab
Enrollment 243
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Arm A: Placebo + Trastuzumab + Docetaxel Arm B: Pertuzumab + Trastuzumab + Docetaxel
Hide Arm/Group Description Placebo matched to pertuzumab, trastuzumab (8-milligrams per kilogram [mg/kg] loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-milligrams per square meter [mg/m^2]), administered by intravenous (IV) infusion every 3 weeks until disease progression or unacceptable toxicity. Pertuzumab (840-mg loading dose for Cycle 1, followed by 420 mg for subsequent cycles), trastuzumab (8-mg/kg loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-mg/m^2), administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity.
Period Title: Overall Study
Started [1] 121 122
Received Any Study Treatment [2] 120 122
Completed 0 0
Not Completed 121 122
Reason Not Completed
On Study Treatment             41             60
In Follow-Up             61             49
Death             13             12
Lost to Follow-up             5             0
Withdrawal by Subject             1             1
[1]
Intent-to-Treat (ITT) Population
[2]
Safety Population
Arm/Group Title Arm A: Placebo + Trastuzumab + Docetaxel Arm B: Pertuzumab + Trastuzumab + Docetaxel Total
Hide Arm/Group Description Placebo matched to pertuzumab, trastuzumab (8-milligrams per kilogram [mg/kg] loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-milligrams per square meter [mg/m^2]), administered by intravenous (IV) infusion every 3 weeks until disease progression or unacceptable toxicity. Pertuzumab (840-mg loading dose for Cycle 1, followed by 420 mg for subsequent cycles), trastuzumab (8-mg/kg loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-mg/m^2), administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity. Total of all reporting groups
Overall Number of Baseline Participants 121 122 243
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 121 participants 122 participants 243 participants
51.3  (11.2) 50.7  (10.6) 51.0  (10.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 121 participants 122 participants 243 participants
Female
121
 100.0%
122
 100.0%
243
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 121 participants 122 participants 243 participants
Asian
121
 100.0%
122
 100.0%
243
 100.0%
Disease Type: Visceral or Non-Visceral Disease  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 121 participants 122 participants 243 participants
Visceral Disease
86
  71.1%
88
  72.1%
174
  71.6%
Non-Visceral Disease
35
  28.9%
34
  27.9%
69
  28.4%
Hormone Receptor Status  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 121 participants 122 participants 243 participants
Estrogen and Progesterone Receptor Negative
48
  39.7%
53
  43.4%
101
  41.6%
Estrogen and/or Progesterone Receptor Positive
73
  60.3%
69
  56.6%
142
  58.4%
Measurable or Non-Measurable Disease, According to RECIST v1.1  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 121 participants 122 participants 243 participants
Measurable Disease
97
  80.2%
105
  86.1%
202
  83.1%
Non-Measurable Disease
24
  19.8%
17
  13.9%
41
  16.9%
1.Primary Outcome
Title Progression-Free Survival, as Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
Hide Description Progression-free survival (PFS) was defined as the time from randomization to first occurrence of progressive disease (PD), as determined by the investigator using RECIST v1.1, or death from any cause within 18 weeks after the last tumor assessment, whichever occurred first. As per RECIST v1.1, PD is defined as a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 millimeters (mm), and the appearance of new lesions. The Kaplan-Meier approach was used to estimate median PFS for each treatment arm. Data for participants who did not have a PFS event were censored at the time of the last tumor assessment (if no tumor assessments performed after baseline, at randomization plus 1 day). At the primary completion date, mean (standard deviation) duration of time on study in Arms A and B were 57.74 (19.14) weeks and 59.46 (16.80) weeks, respectively.
Time Frame From date of randomization until date of first documented PD or date of death from any cause within 18 weeks after the last tumor assessment, whichever occurs first (up to approximately 3 years)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Arm A: Placebo + Trastuzumab + Docetaxel Arm B: Pertuzumab + Trastuzumab + Docetaxel
Hide Arm/Group Description:
Placebo matched to pertuzumab, trastuzumab (8-milligrams per kilogram [mg/kg] loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-milligrams per square meter [mg/m^2]), administered by intravenous (IV) infusion every 3 weeks until disease progression or unacceptable toxicity.
Pertuzumab (840-mg loading dose for Cycle 1, followed by 420 mg for subsequent cycles), trastuzumab (8-mg/kg loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-mg/m^2), administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 121 122
Median (95% Confidence Interval)
Unit of Measure: months
12.4
(10.4 to 12.7)
14.5
(12.5 to 18.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A: Placebo + Trastuzumab + Docetaxel, Arm B: Pertuzumab + Trastuzumab + Docetaxel
Comments Hypothesis testing is considered exploratory in this bridging study.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0418
Comments [Not Specified]
Method Log Rank
Comments A two-sided log-rank test was used, stratified by disease type and hormone-receptor status.
Method of Estimation Estimation Parameter Stratified Hazard Ratio
Estimated Value 0.69
Confidence Interval (2-Sided) 95%
0.49 to 0.99
Estimation Comments This stratified Hazard Ratio (HR) is calculated as Arm B: Pertuzumab versus Arm A: Placebo. Cox proportional hazards model, stratified by disease type and hormone-receptor status, was used to estimate HR and its 95% CI.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Arm A: Placebo + Trastuzumab + Docetaxel, Arm B: Pertuzumab + Trastuzumab + Docetaxel
Comments Hypothesis testing is considered exploratory in this bridging study.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0556
Comments [Not Specified]
Method Log Rank
Comments This two-sided log-rank test was unstratified.
Method of Estimation Estimation Parameter Unstratified Hazard Ratio
Estimated Value 0.71
Confidence Interval (2-Sided) 95%
0.50 to 1.01
Estimation Comments This unstratified Hazard Ratio (HR) is calculated as Arm B: Pertuzumab versus Arm A: Placebo. Cox proportional hazards model was used to estimate HR and its 95% CI.
2.Primary Outcome
Title Percentage of Participants With 1 Year of Progression-Free Survival, as Determined by the Investigator Using RECIST v1.1
Hide Description Progression-free survival (PFS) was defined as the time from randomization to first occurrence of progressive disease (PD), as determined by the investigator using RECIST v1.1, or death from any cause within 18 weeks after the last tumor assessment, whichever occurred first. As per RECIST v1.1, PD is a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 mm, and the appearance of new lesions. The Kaplan-Meier approach was used to estimate the percentage of participants with 1 year of PFS for each treatment arm. Data for participants who did not have a PFS event were censored at the time of the last tumor assessment (if no tumor assessments performed after baseline visit, at randomization plus 1 day). At the primary completion date, mean (standard deviation) duration of time on study in Arms A and B were 57.74 (19.14) and 59.46 (16.80) weeks, respectively.
Time Frame From date of randomization until date of first documented PD or date of death from any cause within 18 weeks after the last tumor assessment, whichever occurs first (up to 1 year)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Arm A: Placebo + Trastuzumab + Docetaxel Arm B: Pertuzumab + Trastuzumab + Docetaxel
Hide Arm/Group Description:
Placebo matched to pertuzumab, trastuzumab (8-milligrams per kilogram [mg/kg] loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-milligrams per square meter [mg/m^2]), administered by intravenous (IV) infusion every 3 weeks until disease progression or unacceptable toxicity.
Pertuzumab (840-mg loading dose for Cycle 1, followed by 420 mg for subsequent cycles), trastuzumab (8-mg/kg loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-mg/m^2), administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 121 122
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: estimate of percentage of participants
52.53
(43.16 to 61.91)
65.83
(57.18 to 74.47)
3.Secondary Outcome
Title Overall Survival
Hide Description Overall survival (OS) was defined as the time from randomization to death from any cause. The Kaplan-Meier approach was used to estimate median OS for each treatment arm. Participants who were alive or lost to follow-up at the time of the analysis were censored at the date they were last known to be alive. Participants with no post-baseline information were censored at the time of randomization plus 1 day. At the primary completion date, mean (standard deviation) duration of time on study in Arms A and B were 57.74 (19.14) weeks and 59.46 (16.80) weeks, respectively.
Time Frame From date of randomization until the date of death from any cause (up to approximately 3 years)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population; At the primary completion date, the median duration of OS had not been reached and OS data was not considered mature due to the few number of events reported. Survival follow-up is ongoing, and results will be reported upon study completion.
Arm/Group Title Arm A: Placebo + Trastuzumab + Docetaxel Arm B: Pertuzumab + Trastuzumab + Docetaxel
Hide Arm/Group Description:
Placebo matched to pertuzumab, trastuzumab (8-milligrams per kilogram [mg/kg] loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-milligrams per square meter [mg/m^2]), administered by intravenous (IV) infusion every 3 weeks until disease progression or unacceptable toxicity.
Pertuzumab (840-mg loading dose for Cycle 1, followed by 420 mg for subsequent cycles), trastuzumab (8-mg/kg loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-mg/m^2), administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 121 122
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
At the primary completion date, the median duration of OS had not been reached and OS data was not considered mature due to the few number of events reported. Survival follow-up is ongoing.
4.Secondary Outcome
Title Percentage of Participants With 1 Year of Overall Survival
Hide Description Overall survival (OS) was defined as the time from randomization to death from any cause. The Kaplan-Meier approach was used to estimate the percentage of participants with 1 year of OS. Participants who were alive or lost to follow-up at the time of the analysis were censored at the date they were last known to be alive. Participants with no post-baseline information were censored at the time of randomization plus 1 day. At the primary completion date, mean (standard deviation) duration of time on study in Arms A and B were 57.74 (19.14) weeks and 59.46 (16.80) weeks, respectively.
Time Frame From date of randomization until the date of death from any cause (up to 1 year)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Arm A: Placebo + Trastuzumab + Docetaxel Arm B: Pertuzumab + Trastuzumab + Docetaxel
Hide Arm/Group Description:
Placebo matched to pertuzumab, trastuzumab (8-milligrams per kilogram [mg/kg] loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-milligrams per square meter [mg/m^2]), administered by intravenous (IV) infusion every 3 weeks until disease progression or unacceptable toxicity.
Pertuzumab (840-mg loading dose for Cycle 1, followed by 420 mg for subsequent cycles), trastuzumab (8-mg/kg loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-mg/m^2), administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 121 122
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: estimate of percentage of participants
92.29
(87.44 to 97.13)
93.19
(88.62 to 97.76)
5.Secondary Outcome
Title Percentage of Participants With Measurable Disease at Baseline Who Achieved an Objective Response (Complete or Partial Response), as Determined by the Investigator Using RECIST v1.1
Hide Description An objective response was defined as a complete response (CR) or partial response (PR), as determined by the investigator using RECIST v1.1. As per RECIST v1.1, CR is defined as the disappearance of all target lesions, and PR is defined as at least a 30% decrease in the sum of diameters of target lesions. Also per RECIST v1.1, stable disease (SD) is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum on study; PD is defined as a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 mm, and the appearance of new lesions. The same assessment technique must be used throughout the study for evaluating a particular lesion, and the same investigator should assess all tumor responses for each participant. Participants without a post-baseline tumor assessment were considered non-responders.
Time Frame At Baseline and every 9 weeks from date of randomization until disease progression or death, whichever occurs first (up to approximately 3 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Only participants with measurable disease at baseline were included in the analysis.
Arm/Group Title Arm A: Placebo + Trastuzumab + Docetaxel Arm B: Pertuzumab + Trastuzumab + Docetaxel
Hide Arm/Group Description:
Placebo matched to pertuzumab, trastuzumab (8-milligrams per kilogram [mg/kg] loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-milligrams per square meter [mg/m^2]), administered by intravenous (IV) infusion every 3 weeks until disease progression or unacceptable toxicity.
Pertuzumab (840-mg loading dose for Cycle 1, followed by 420 mg for subsequent cycles), trastuzumab (8-mg/kg loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-mg/m^2), administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 97 105
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Objective Response (CR + PR)
69.1
(58.88 to 78.07)
79.0
(70.01 to 86.38)
Complete Response (CR)
8.2
(3.63 to 15.61)
5.7
(2.13 to 12.02)
Partial Response (PR)
60.8
(50.39 to 70.58)
73.3
(63.81 to 81.49)
Stable Disease (SD)
20.6
(13.07 to 30.03)
15.2
(8.97 to 23.56)
Progressive Disease (PD)
4.1
(1.13 to 10.22)
3.8
(1.05 to 9.47)
Missing or Unevaluable
6.2 [1] 
(NA to NA)
1.9 [1] 
(NA to NA)
[1]
95% confidence intervals were only calculated for responses.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A: Placebo + Trastuzumab + Docetaxel, Arm B: Pertuzumab + Trastuzumab + Docetaxel
Comments Hypothesis testing is considered exploratory in this bridging study.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1126
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Statistical test is stratified by disease type and hormone receptor status.
Method of Estimation Estimation Parameter Difference in Objective Response
Estimated Value 9.98
Confidence Interval (2-Sided) 95%
-2.65 to 22.60
Estimation Comments The difference in objective response is calculated as Arm B: Pertuzumab minus Arm A: Placebo. 95% CI was calculated using Hauck-Anderson method.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Arm A: Placebo + Trastuzumab + Docetaxel, Arm B: Pertuzumab + Trastuzumab + Docetaxel
Comments Hypothesis testing is considered exploratory in this bridging study.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1108
Comments [Not Specified]
Method Fisher Exact
Comments Unadjusted
Method of Estimation Estimation Parameter Difference in Objective Response
Estimated Value 9.98
Confidence Interval (2-Sided) 95%
-2.65 to 22.60
Estimation Comments The difference in objective response is calculated as Arm B: Pertuzumab minus Arm A: Placebo. 95% CI was calculated using Hauck-Anderson method.
6.Secondary Outcome
Title Duration of Objective Response, as Determined by the Investigator Using RECIST v1.1
Hide Description Duration of objective response was defined as the time from the first occurrence of a documented objective response (complete response [CR] or partial response [PR]) to the time of disease progression, as determined by the investigator using RECIST v1.1, or death from any cause within 18 weeks after the last tumor assessment, whichever occurred first. As per RECIST v1.1, CR is defined as the disappearance of all target lesions, and PR is defined as at least a 30% decrease in the sum of diameters of target lesions. The Kaplan-Meier approach was used to estimate median duration of objective response. Data for participants who did not have an event were censored at the time of the last tumor assessment (if no tumor assessments were performed after baseline visit, at randomization plus 1 day). At the primary completion date, mean (standard deviation) duration of time on study in Arms A and B were 57.74 (19.14) weeks and 59.46 (16.80) weeks, respectively.
Time Frame From date of first occurrence of documented objective response to date of progressive disease or date of death from any cause within 18 weeks after the last tumor assessment, whichever occurs first (up to approximately 3 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Only participants with measurable disease at baseline who achieved an objective response during the study were included in the analysis.
Arm/Group Title Arm A: Placebo + Trastuzumab + Docetaxel Arm B: Pertuzumab + Trastuzumab + Docetaxel
Hide Arm/Group Description:
Placebo matched to pertuzumab, trastuzumab (8-milligrams per kilogram [mg/kg] loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-milligrams per square meter [mg/m^2]), administered by intravenous (IV) infusion every 3 weeks until disease progression or unacceptable toxicity.
Pertuzumab (840-mg loading dose for Cycle 1, followed by 420 mg for subsequent cycles), trastuzumab (8-mg/kg loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-mg/m^2), administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 67 83
Median (95% Confidence Interval)
Unit of Measure: months
10.4
(8.3 to 15.4)
12.4
(10.6 to 14.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A: Placebo + Trastuzumab + Docetaxel, Arm B: Pertuzumab + Trastuzumab + Docetaxel
Comments Hypothesis testing is considered exploratory in this bridging study.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2867
Comments [Not Specified]
Method Log Rank
Comments Two-sided log-rank test was used, stratified by disease type and hormone-receptor status.
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 0.78
Confidence Interval (2-Sided) 95%
0.49 to 1.24
Estimation Comments This stratified Hazard Ratio (HR) is calculated as Arm B: Pertuzumab versus Arm A: Placebo. Cox proportional hazards model, stratified by disease type and hormone-receptor status, was used to estimate HR and its 95% CI.
7.Secondary Outcome
Title Number of Participants With at Least One Adverse Event
Hide Description The number of participants experiencing at least one adverse event, including all non-serious and serious adverse events, is reported here. At the primary completion date, the mean (standard deviation) duration of time that participants were on study in Arms A and B were 57.74 (19.14) weeks and 59.46 (16.80) weeks, respectively.
Time Frame From Baseline up to 3 years after treatment discontinuation
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population, which includes participants who received at least one dose of any study drug.
Arm/Group Title Arm A: Placebo + Trastuzumab + Docetaxel Arm B: Pertuzumab + Trastuzumab + Docetaxel
Hide Arm/Group Description:
Placebo matched to pertuzumab, trastuzumab (8-milligrams per kilogram [mg/kg] loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-milligrams per square meter [mg/m^2]), administered by intravenous (IV) infusion every 3 weeks until disease progression or unacceptable toxicity.
Pertuzumab (840-mg loading dose for Cycle 1, followed by 420 mg for subsequent cycles), trastuzumab (8-mg/kg loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-mg/m^2), administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 120 122
Measure Type: Count of Participants
Unit of Measure: Participants
115
  95.8%
120
  98.4%
8.Secondary Outcome
Title Number of Participants With at Least One Grade ≥3 Adverse Event
Hide Description The adverse event severity grading scale for the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (NCI CTCAE v4.0) was used for assessing the severity of adverse events. At the primary completion date, the mean (standard deviation) duration of time that participants were on study in Arms A and B were 57.74 (19.14) weeks and 59.46 (16.80) weeks, respectively.
Time Frame From Baseline up to 3 years after treatment discontinuation
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population, which includes participants who received at least one dose of any study drug.
Arm/Group Title Arm A: Placebo + Trastuzumab + Docetaxel Arm B: Pertuzumab + Trastuzumab + Docetaxel
Hide Arm/Group Description:
Placebo matched to pertuzumab, trastuzumab (8-milligrams per kilogram [mg/kg] loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-milligrams per square meter [mg/m^2]), administered by intravenous (IV) infusion every 3 weeks until disease progression or unacceptable toxicity.
Pertuzumab (840-mg loading dose for Cycle 1, followed by 420 mg for subsequent cycles), trastuzumab (8-mg/kg loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-mg/m^2), administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 120 122
Measure Type: Count of Participants
Unit of Measure: Participants
83
  69.2%
86
  70.5%
9.Secondary Outcome
Title Number of Participants With at Least One Adverse Event Leading to Withdrawal From Any Treatment
Hide Description At the primary completion date, the mean (standard deviation) duration of time that participants were on study in Arms A and B were 57.74 (19.14) weeks and 59.46 (16.80) weeks, respectively.
Time Frame From Baseline up to 3 years after treatment discontinuation
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population, which includes participants who received at least one dose of any study drug.
Arm/Group Title Arm A: Placebo + Trastuzumab + Docetaxel Arm B: Pertuzumab + Trastuzumab + Docetaxel
Hide Arm/Group Description:
Placebo matched to pertuzumab, trastuzumab (8-milligrams per kilogram [mg/kg] loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-milligrams per square meter [mg/m^2]), administered by intravenous (IV) infusion every 3 weeks until disease progression or unacceptable toxicity.
Pertuzumab (840-mg loading dose for Cycle 1, followed by 420 mg for subsequent cycles), trastuzumab (8-mg/kg loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-mg/m^2), administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 120 122
Measure Type: Count of Participants
Unit of Measure: Participants
10
   8.3%
16
  13.1%
10.Secondary Outcome
Title Number of Participants With Symptomatic Left Ventricular Systolic Dysfunction (LVSD), as Determined Using Echocardiography (ECHO) or Multiple-Gated Acquisition (MUGA) Scan
Hide Description The number of participants with symptomatic left ventricular systolic dysfunction (LVSD) at any time during the study, as determined using echocardiography (ECHO) or multiple-gated acquisition (MUGA) scan, were summarized by treatment arm. Symptomatic LVSD was evaluated according to NCI CTCAE v4.0 (for "heart failure") and the New York Heart Association (NYHA) classification. At the primary completion date, the mean (standard deviation) duration of time that participants were on study in Arms A and B were 57.74 (19.14) weeks and 59.46 (16.80) weeks, respectively.
Time Frame Baseline, every 9 weeks from the date of randomization until the treatment discontinuation visit, then every 6 months for the first year and annually thereafter for up to 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population, which includes participants who received at least one dose of any study drug.
Arm/Group Title Arm A: Placebo + Trastuzumab + Docetaxel Arm B: Pertuzumab + Trastuzumab + Docetaxel
Hide Arm/Group Description:
Placebo matched to pertuzumab, trastuzumab (8-milligrams per kilogram [mg/kg] loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-milligrams per square meter [mg/m^2]), administered by intravenous (IV) infusion every 3 weeks until disease progression or unacceptable toxicity.
Pertuzumab (840-mg loading dose for Cycle 1, followed by 420 mg for subsequent cycles), trastuzumab (8-mg/kg loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-mg/m^2), administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 120 122
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
11.Secondary Outcome
Title Number of Participants With an Asymptomatic Left Ventricular Ejection Fraction (LVEF) Event, as Determined Using ECHO or MUGA Scan
Hide Description An asymptomatic LVEF event is reported as an adverse event of "ejection fraction decreased" and is defined as either of the following: an absolute decrease in LVEF of ≥10 percentage points from baseline to an LVEF of <50%; or an asymptomatic decrease in LVEF requiring treatment or leading to discontinuation of pertuzumab (or placebo) and trastuzumab. At the primary completion date, the mean (standard deviation) duration of time that participants were on study in Arms A and B were 57.74 (19.14) weeks and 59.46 (16.80) weeks, respectively.
Time Frame Baseline, every 9 weeks from the date of randomization until the treatment discontinuation visit, then every 6 months for the first year and annually thereafter for up to 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population, which includes participants who received at least one dose of any study drug.
Arm/Group Title Arm A: Placebo + Trastuzumab + Docetaxel Arm B: Pertuzumab + Trastuzumab + Docetaxel
Hide Arm/Group Description:
Placebo matched to pertuzumab, trastuzumab (8-milligrams per kilogram [mg/kg] loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-milligrams per square meter [mg/m^2]), administered by intravenous (IV) infusion every 3 weeks until disease progression or unacceptable toxicity.
Pertuzumab (840-mg loading dose for Cycle 1, followed by 420 mg for subsequent cycles), trastuzumab (8-mg/kg loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-mg/m^2), administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 120 122
Measure Type: Count of Participants
Unit of Measure: Participants
1
   0.8%
2
   1.6%
12.Secondary Outcome
Title Change From Baseline in LVEF Over Time, as Determined Using ECHO or MUGA Scan
Hide Description Here, we report the change from baseline in LVEF over time. Left ventricular ejection fraction (LVEF) is the measurement of how much blood is being pumped out of the left ventricle of the heart (the main pumping chamber) with each contraction. LVEF was calculated using the modified Simpson method and must have been ≥55% at baseline as determined by the local facility before a participant could be enrolled in the study. The investigator must have decided which method of LVEF assessment (ECHO [preferred] or MUGA scan) would be used for each participant at baseline, and the same method should have been used throughout the study, to the extent possible. At the primary completion date, the mean (standard deviation) duration of time that participants were on study in Arms A and B were 57.74 (19.14) weeks and 59.46 (16.80) weeks, respectively.
Time Frame Baseline, every 9 weeks from the date of randomization until the treatment discontinuation visit, then every 6 months for the first year and annually thereafter for up to 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population, which includes participants who received at least one dose of any study drug. Number analyzed indicates the number of participants with a post-baseline LVEF measurement at each time point.
Arm/Group Title Arm A: Placebo + Trastuzumab + Docetaxel Arm B: Pertuzumab + Trastuzumab + Docetaxel
Hide Arm/Group Description:
Placebo matched to pertuzumab, trastuzumab (8-milligrams per kilogram [mg/kg] loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-milligrams per square meter [mg/m^2]), administered by intravenous (IV) infusion every 3 weeks until disease progression or unacceptable toxicity.
Pertuzumab (840-mg loading dose for Cycle 1, followed by 420 mg for subsequent cycles), trastuzumab (8-mg/kg loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-mg/m^2), administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 120 122
Mean (95% Confidence Interval)
Unit of Measure: percentage points of LVEF
Change from Baseline at Week 9 Number Analyzed 111 participants 119 participants
-0.41
(-1.23 to 0.42)
-0.09
(-0.96 to 0.78)
Change from Baseline at Week 18 Number Analyzed 98 participants 111 participants
0.10
(-0.90 to 1.11)
-0.24
(-1.15 to 0.67)
Change from Baseline at Week 27 Number Analyzed 92 participants 99 participants
-0.49
(-1.52 to 0.55)
-0.55
(-1.54 to 0.44)
Change from Baseline at Week 36 Number Analyzed 76 participants 94 participants
-0.45
(-1.70 to 0.79)
-0.98
(-2.10 to 0.14)
Change from Baseline at Week 45 Number Analyzed 64 participants 79 participants
-0.82
(-2.35 to 0.71)
-1.88
(-3.03 to -0.72)
Change from Baseline at Week 54 Number Analyzed 47 participants 60 participants
-1.45
(-3.28 to 0.38)
-1.11
(-2.37 to 0.14)
Change from Baseline at Week 63 Number Analyzed 26 participants 34 participants
-2.33
(-4.58 to -0.09)
-0.78
(-2.42 to 0.87)
Change from Baseline at Week 72 Number Analyzed 16 participants 21 participants
-2.06
(-5.71 to 1.58)
-1.53
(-3.96 to 0.90)
Change from Baseline at Week 81 Number Analyzed 9 participants 8 participants
-1.22
(-8.22 to 5.78)
0.00
(-3.43 to 3.43)
Change from Baseline at Week 90 Number Analyzed 2 participants 2 participants
2.00
(-10.71 to 14.71)
-1.00
(-13.71 to 11.71)
13.Secondary Outcome
Title Change From Baseline to Maximum On-Treatment Decrease in LVEF at Any Point During the Study
Hide Description The baseline left ventricular ejection fraction (LVEF) and change from baseline to the maximum on-treatment decrease in LVEF at any point during the study are reported here. LVEF is the measurement of how much blood is being pumped out of the left ventricle of the heart (the main pumping chamber) with each contraction. LVEF was calculated using the modified Simpson method and must have been ≥55% at baseline as determined by the local facility before a participant could be enrolled in the study. The investigator decided which method of LVEF assessment (ECHO [preferred] or MUGA scan) would be used for each participant at baseline, and the same method should have been used throughout the study, to the extent possible. At the primary completion date, the mean (standard deviation) duration of time that participants were on study in Arms A and B were 57.74 (19.14) weeks and 59.46 (16.80) weeks, respectively.
Time Frame Baseline and every 9 weeks from date of randomization until treatment discontinuation (up to approximately 3 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population, which includes participants who received at least one dose of any study drug. Number analyzed indicates participants with a baseline LVEF measurement and at least one post-baseline LVEF measurement, respectively.
Arm/Group Title Arm A: Placebo + Trastuzumab + Docetaxel Arm B: Pertuzumab + Trastuzumab + Docetaxel
Hide Arm/Group Description:
Placebo matched to pertuzumab, trastuzumab (8-milligrams per kilogram [mg/kg] loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-milligrams per square meter [mg/m^2]), administered by intravenous (IV) infusion every 3 weeks until disease progression or unacceptable toxicity.
Pertuzumab (840-mg loading dose for Cycle 1, followed by 420 mg for subsequent cycles), trastuzumab (8-mg/kg loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-mg/m^2), administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 120 122
Mean (Standard Deviation)
Unit of Measure: percentage points of LVEF
Baseline LVEF (value at visit) Number Analyzed 119 participants 122 participants
64.23  (4.90) 65.08  (4.43)
Change from Baseline to Max Decrease in LVEF Number Analyzed 111 participants 119 participants
-4.09  (4.91) -4.60  (4.96)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A: Placebo + Trastuzumab + Docetaxel, Arm B: Pertuzumab + Trastuzumab + Docetaxel
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -0.51
Confidence Interval (2-Sided) 95%
-1.79 to 0.77
Estimation Comments The treatment difference for change from baseline to maximum on-treatment decrease in LVEF is defined as Arm B: Pertuzumab minus Arm A: Placebo.
Time Frame From Baseline until the primary completion date (27-June-2018), adverse event data were collected over the course of approximately 1 year, 10 months. As of the primary completion date, the mean (standard deviation) duration of time that participants were on study in Arms A and B were 57.74 (19.14) weeks and 59.46 (16.80) weeks, respectively.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Arm A: Placebo + Trastuzumab + Docetaxel Arm B: Pertuzumab + Trastuzumab + Docetaxel
Hide Arm/Group Description Placebo matched to pertuzumab, trastuzumab (8-milligrams per kilogram [mg/kg] loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-milligrams per square meter [mg/m^2]), administered by intravenous (IV) infusion every 3 weeks until disease progression or unacceptable toxicity. Pertuzumab (840-mg loading dose for Cycle 1, followed by 420 mg for subsequent cycles), trastuzumab (8-mg/kg loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-mg/m^2), administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity.
All-Cause Mortality
Arm A: Placebo + Trastuzumab + Docetaxel Arm B: Pertuzumab + Trastuzumab + Docetaxel
Affected / at Risk (%) Affected / at Risk (%)
Total   13/120 (10.83%)   12/122 (9.84%) 
Show Serious Adverse Events Hide Serious Adverse Events
Arm A: Placebo + Trastuzumab + Docetaxel Arm B: Pertuzumab + Trastuzumab + Docetaxel
Affected / at Risk (%) Affected / at Risk (%)
Total   23/120 (19.17%)   24/122 (19.67%) 
Blood and lymphatic system disorders     
Febrile neutropenia  1  4/120 (3.33%)  3/122 (2.46%) 
Leukopenia  1  2/120 (1.67%)  3/122 (2.46%) 
Neutropenia  1  8/120 (6.67%)  9/122 (7.38%) 
Cardiac disorders     
Cardiac tamponade  1  0/120 (0.00%)  2/122 (1.64%) 
Ventricular arrhythmia  1  1/120 (0.83%)  0/122 (0.00%) 
Gastrointestinal disorders     
Ascites  1  0/120 (0.00%)  1/122 (0.82%) 
Oesophagitis  1  0/120 (0.00%)  1/122 (0.82%) 
General disorders     
Death  1  1/120 (0.83%)  1/122 (0.82%) 
Hepatobiliary disorders     
Liver injury  1  1/120 (0.83%)  0/122 (0.00%) 
Infections and infestations     
Lung infection  1  1/120 (0.83%)  0/122 (0.00%) 
Pneumonia  1  2/120 (1.67%)  3/122 (2.46%) 
Upper respiratory tract infection  1  0/120 (0.00%)  1/122 (0.82%) 
Injury, poisoning and procedural complications     
Fracture  1  1/120 (0.83%)  0/122 (0.00%) 
Investigations     
Alanine aminotransferase increased  1  2/120 (1.67%)  0/122 (0.00%) 
Aspartate aminotransferase increased  1  1/120 (0.83%)  0/122 (0.00%) 
Blood glucose increased  1  0/120 (0.00%)  1/122 (0.82%) 
Metabolism and nutrition disorders     
Hyperuricaemia  1  1/120 (0.83%)  0/122 (0.00%) 
Nervous system disorders     
Dizziness  1  0/120 (0.00%)  1/122 (0.82%) 
Reproductive system and breast disorders     
Metrorrhagia  1  1/120 (0.83%)  0/122 (0.00%) 
Pelvic prolapse  1  0/120 (0.00%)  1/122 (0.82%) 
Respiratory, thoracic and mediastinal disorders     
Respiratory failure  1  1/120 (0.83%)  0/122 (0.00%) 
1
Term from vocabulary, MedDRA v21.0
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Arm A: Placebo + Trastuzumab + Docetaxel Arm B: Pertuzumab + Trastuzumab + Docetaxel
Affected / at Risk (%) Affected / at Risk (%)
Total   114/120 (95.00%)   117/122 (95.90%) 
Blood and lymphatic system disorders     
Anaemia  1  57/120 (47.50%)  64/122 (52.46%) 
Leukopenia  1  86/120 (71.67%)  89/122 (72.95%) 
Neutropenia  1  80/120 (66.67%)  85/122 (69.67%) 
Thrombocytopenia  1  11/120 (9.17%)  6/122 (4.92%) 
Gastrointestinal disorders     
Abdominal distension  1  6/120 (5.00%)  6/122 (4.92%) 
Abdominal pain upper  1  8/120 (6.67%)  7/122 (5.74%) 
Constipation  1  10/120 (8.33%)  7/122 (5.74%) 
Diarrhoea  1  26/120 (21.67%)  56/122 (45.90%) 
Flatulence  1  4/120 (3.33%)  7/122 (5.74%) 
Mouth ulceration  1  6/120 (5.00%)  10/122 (8.20%) 
Nausea  1  14/120 (11.67%)  13/122 (10.66%) 
Stomatitis  1  4/120 (3.33%)  14/122 (11.48%) 
Vomiting  1  9/120 (7.50%)  13/122 (10.66%) 
General disorders     
Asthenia  1  20/120 (16.67%)  25/122 (20.49%) 
Fatigue  1  6/120 (5.00%)  5/122 (4.10%) 
Influenza like illness  1  6/120 (5.00%)  9/122 (7.38%) 
Malaise  1  11/120 (9.17%)  9/122 (7.38%) 
Oedema peripheral  1  18/120 (15.00%)  10/122 (8.20%) 
Pain  1  22/120 (18.33%)  18/122 (14.75%) 
Pyrexia  1  18/120 (15.00%)  26/122 (21.31%) 
Hepatobiliary disorders     
Hepatic function abnormal  1  6/120 (5.00%)  3/122 (2.46%) 
Infections and infestations     
Nasopharyngitis  1  6/120 (5.00%)  4/122 (3.28%) 
Upper respiratory tract infection  1  13/120 (10.83%)  11/122 (9.02%) 
Investigations     
Alanine aminotransferase increased  1  50/120 (41.67%)  35/122 (28.69%) 
Aspartate aminotransferase increased  1  42/120 (35.00%)  33/122 (27.05%) 
Blood alkaline phosphatase increased  1  7/120 (5.83%)  6/122 (4.92%) 
Blood bilirubin increased  1  13/120 (10.83%)  10/122 (8.20%) 
Blood creatinine increased  1  8/120 (6.67%)  8/122 (6.56%) 
Blood triglycerides increased  1  4/120 (3.33%)  7/122 (5.74%) 
Gamma-glutamyltransferase increased  1  10/120 (8.33%)  6/122 (4.92%) 
Weight decreased  1  6/120 (5.00%)  10/122 (8.20%) 
Weight increased  1  15/120 (12.50%)  4/122 (3.28%) 
Metabolism and nutrition disorders     
Decreased appetite  1  14/120 (11.67%)  15/122 (12.30%) 
Hyperglycaemia  1  8/120 (6.67%)  10/122 (8.20%) 
Hypoalbuminaemia  1  7/120 (5.83%)  8/122 (6.56%) 
Hypokalaemia  1  7/120 (5.83%)  15/122 (12.30%) 
Hypoproteinaemia  1  3/120 (2.50%)  7/122 (5.74%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  1/120 (0.83%)  7/122 (5.74%) 
Back pain  1  3/120 (2.50%)  7/122 (5.74%) 
Pain in extremity  1  7/120 (5.83%)  5/122 (4.10%) 
Nervous system disorders     
Dizziness  1  10/120 (8.33%)  6/122 (4.92%) 
Headache  1  8/120 (6.67%)  7/122 (5.74%) 
Hypoaesthesia  1  8/120 (6.67%)  13/122 (10.66%) 
Neurotoxicity  1  7/120 (5.83%)  10/122 (8.20%) 
Psychiatric disorders     
Insomnia  1  9/120 (7.50%)  9/122 (7.38%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  14/120 (11.67%)  23/122 (18.85%) 
Oropharyngeal pain  1  2/120 (1.67%)  7/122 (5.74%) 
Skin and subcutaneous tissue disorders     
Alopecia  1  40/120 (33.33%)  50/122 (40.98%) 
Dermatitis acneiform  1  2/120 (1.67%)  7/122 (5.74%) 
Nail discolouration  1  15/120 (12.50%)  12/122 (9.84%) 
Pruritus  1  6/120 (5.00%)  6/122 (4.92%) 
Rash  1  9/120 (7.50%)  10/122 (8.20%) 
Vascular disorders     
Hypertension  1  8/120 (6.67%)  4/122 (3.28%) 
1
Term from vocabulary, MedDRA v21.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Communications
Organization: Hoffmann-La Roche
Phone: 800-821-8590
EMail: genentech@druginfo.com
Layout table for additonal information
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02896855     History of Changes
Other Study ID Numbers: YO29296
First Submitted: September 7, 2016
First Posted: September 12, 2016
Results First Submitted: June 18, 2019
Results First Posted: July 10, 2019
Last Update Posted: September 18, 2019