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Trial record 42 of 167 for:    pertuzumab

Corrected QT Interval Effects of Trastuzumab Emtansine (T-DM1) in Patients With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Locally Advanced or Metastatic Breast Cancer and the Safety and Tolerability of Combined T-DM1 and Pertuzumab in Patients With Early Disease Progression

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ClinicalTrials.gov Identifier: NCT00943670
Recruitment Status : Completed
First Posted : July 22, 2009
Results First Posted : May 1, 2013
Last Update Posted : May 27, 2013
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Metastatic Breast Cancer
Interventions Biological: pertuzumab
Biological: Trastuzumab emtansine [Kadcyla]
Enrollment 51
Recruitment Details Between 14 July 2009 and 4 December 2009, 51 patients from 13 study sites in the United States were enrolled and initiated treatment in the study.
Pre-assignment Details All patients enrolled in the study were initially treated with single-agent trastuzumab emtansine. Participants with early progressive disease could elect to receive pertuzumab in combination with trastuzumab emtansine.
Arm/Group Title T-DM1 / T-DM1 + Pertuzumab
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Trastuzumab emtansine (T-DM1) was administered to participants by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.

From Cycle 4, participants with early Progressive disease (demonstrated prior to the end of Cycle 6) could receive combined pertuzumab and trastuzumab emtansine. Pertuzumab was administered after trastuzumab emtansine by IV infusion at a loading dose of 840 mg on Day 1, starting at the cycle after tumor progression was determined, followed by 420 mg IV infusion every 3 weeks in subsequent cycles.

Participants who met criteria for ongoing clinical benefit were allowed to continue study treatment in the absence of disease progression or unacceptable toxicity for up to 1 year.

Period Title: Single-agent Trastuzumab Emtansine
Started 51
Treated 51
Completed 9 [1]
Not Completed 42
Reason Not Completed
Physician Decision             2
Withdrawal by Subject             3
Systemic progression             15
Adverse Event             2
Early progressive disease             20
[1]
Completed single-agent treatment defined as receiving 17 cycles of trastuzumab emtansine therapy.
Period Title: Trastuzumab Emtansine + Pertuzumab
Started 20 [1]
Completed 2 [2]
Not Completed 18
Reason Not Completed
Physician Decision             1
Withdrawal by Subject             4
Systemic progression             6
Progression of brain metastases             2
Adverse Event             5
[1]
Patients with early progressive disease who elected to receive T-DM1 and pertuzumab.
[2]
Completed treatment defined as receiving a total of 17 cycles of therapy in both treatment periods.
Arm/Group Title T-DM1 / T-DM1 + Pertuzumab
Hide Arm/Group Description

Trastuzumab emtansine (T-DM1) was administered to participants by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.

From Cycle 4, participants with early Progressive disease (demonstrated prior to the end of Cycle 6) could receive combined pertuzumab and trastuzumab emtansine. Pertuzumab was administered after trastuzumab emtansine by IV infusion at a loading dose of 840 mg on Day 1, starting at the cycle after tumor progression was determined, followed by 420 mg IV infusion every 3 weeks in subsequent cycles.

Participants who met criteria for ongoing clinical benefit were allowed to continue study treatment in the absence of disease progression or unacceptable toxicity for up to 1 year.

Overall Number of Baseline Participants 51
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 51 participants
53.5  (11.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 51 participants
Female
51
 100.0%
Male
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 51 participants
51
1.Primary Outcome
Title Change From Baseline in Mean Duration of the QTc Interval
Hide Description The QT interval is a measure of time between the start of the Q wave and the end of the T wave in the heart's electrical cycle. The corrected QT interval was calculated using Fridericia’s correction (QTcF) from electrocardiogram (ECG) data. Each participant had triplicate QTcF intervals measured at each timepoint and the average was calculated for each patient at each timepoint. For each timepoint, a participant’s corresponding baseline QTcF interval was subtracted from the average QTcF intervals to create a baseline-adjusted average QTcF interval.
Time Frame Cycle 1 Day 1, pre-dose (Baseline); Cycle 1 Day 1, 15 and 60 minutes post-dose; Cycle 1 Day 8; and Cycle 3 Day 1, 15 minutes pre-dose and 15 and 60 minutes post-dose.
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Hide Analysis Population Description
ECG−evaluable population consisted of patients who received T-DM1, had at least 1 interpretable pre−T-DM1 ECG measurement recorded on Cycle 1 Day 1, had at least 1 interpretable post−T-DM1 ECG measurement and who were not treated with medications that may have altered cardiac conduction. N indicates the ECG−evaluable population at each time point.
Arm/Group Title T-DM1
Hide Arm/Group Description:
Trastuzumab emtansine (T-DM1) was administered to participants by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
Overall Number of Participants Analyzed 51
Mean (Standard Deviation)
Unit of Measure: milliseconds
Cycle 1, Day 1, 15 minutes post-dose [N=44] 1.2  (8.3)
Cycle 1, Day 1, 60 minutes post-dose [N=45] -1.0  (6.3)
Cycle 1, Day 8 [N=43] -4.0  (13.4)
Cycle 3, Day 1, 15 minutes pre−dose [N=35] -0.1  (10.1)
Cycle 3, Day 1, 15 minutes post−dose [N=37] 4.7  (9.6)
Cycle 3, Day 1, 60 minutes post−dose [N=37] 4.7  (10.9)
2.Secondary Outcome
Title Change From Baseline in Mean Duration of the QTc Interval Using Bazett’s Correction
Hide Description The corrected QT interval was calculated using Bazett’s correction (QTcB) from electrocardiogram (ECG) data. Each participant had triplicate QTcB intervals measured at each timepoint and the average was calculated for each patient at each timepoint. For each timepoint, a participant's corresponding baseline QTcB interval was subtracted from the average QTcB intervals to create a baseline-adjusted average QTcB interval.
Time Frame Cycle 1 Day 1, pre-dose (Baseline); Cycle 1 Day 1, 15 and 60 minutes post-dose; Cycle 1 Day 8; and Cycle 3 Day 1, 15 minutes pre-dose and 15 and 60 minutes post-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
ECG−Evaluable population; N indicates the ECG−evaluable population with available data at each time point.
Arm/Group Title T-DM1
Hide Arm/Group Description:
Trastuzumab emtansine (T-DM1) was administered to participants by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
Overall Number of Participants Analyzed 51
Mean (Standard Deviation)
Unit of Measure: milliseconds
Cycle 1, Day 1, 15 minutes post-dose [N=44] 3.6  (9.1)
Cycle 1, Day 1, 60 minutes post-dose [N=45] 2.6  (7.4)
Cycle 1, Day 8 [N=43] 0.7  (13.1)
Cycle 3, Day 1, 15 minutes pre−dose [N=35] 3.7  (14.5)
Cycle 3, Day 1, 15 minutes post−dose [N=37] 6.0  (13.2)
Cycle 3, Day 1, 60 minutes post−dose [N=37] 7.3  (12.2)
3.Secondary Outcome
Title Change From Baseline in Uncorrected QT Interval
Hide Description The uncorrected QT interval was calculated from electrocardiogram (ECG) data. Each participant had triplicate QT intervals measured at each timepoint and the average was calculated for each patient at each timepoint. For each timepoint, a participant's corresponding baseline QT interval was subtracted from the average QT intervals to create a baseline-adjusted average QT interval.
Time Frame Cycle 1 Day 1, pre-dose (Baseline); Cycle 1 Day 1, 15 and 60 minutes post-dose; Cycle 1 Day 8; and Cycle 3 Day 1, 15 minutes pre-dose and 15 and 60 minutes post-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
ECG−Evaluable population; N indicates the ECG−evaluable population with available data at each time point.
Arm/Group Title T-DM1
Hide Arm/Group Description:
Trastuzumab emtansine (T-DM1) was administered to participants by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
Overall Number of Participants Analyzed 51
Mean (Standard Deviation)
Unit of Measure: milliseconds
Cycle 1 Day 1, 15 minutes post-dose [N=44] -2.6  (17.4)
Cycle 1 Day 1, 60 minutes post-dose [N=45] -7.0  (14.9)
Cycle 1 Day 8 [N=43] 12.2  (22.1)
Cycle 3 Day 1, 15 minutes pre-dose [N=35] -7.0  (14.9)
Cycle 3 Day 1, 15 minutes post-dose [N=37] 2.4  (16.4)
Cycle 3 Day 1, 60 minutes post-dose [N=37] 0.1  (19.6)
4.Secondary Outcome
Title Change From Baseline in PR Interval
Hide Description The PR interval is the time in seconds from the beginning of the P wave to the beginning of the QRS complex, and was calculated from electrocardiogram (ECG) data. Each participant had triplicate PR intervals measured at each timepoint and the average was calculated for each patient at each timepoint. For each timepoint, a participant's corresponding baseline PR interval was subtracted from the average PR intervals to create a baseline-adjusted average PR interval.
Time Frame Cycle 1 Day 1, pre-dose (Baseline); Cycle 1 Day 1, 15 and 60 minutes post-dose; Cycle 1 Day 8; and Cycle 3 Day 1, 15 minutes pre-dose and 15 and 60 minutes post-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
ECG-Evaluable population
Arm/Group Title T-DM1
Hide Arm/Group Description:
Trastuzumab emtansine (T-DM1) was administered to participants by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
Overall Number of Participants Analyzed 51
Mean (Standard Deviation)
Unit of Measure: milliseconds
Cycle 1 Day 1, 15 minutes post-dose [N=44] 2.3  (7.5)
Cycle 1 Day 1, 60 minutes post-dose [N=45] 2.5  (8.7)
Cycle 1 Day 8 [N=43] -0.7  (10.7)
Cycle 3 Day 1, 15 minutes pre-dose [N=35] 1.8  (11.0)
Cycle 3 Day 1, 15 minutes post-dose [N=37] 6.7  (9.8)
Cycle 3 Day 1, 60 minutes post-dose [N=37] 5.3  (8.6)
5.Secondary Outcome
Title Change From Baseline in QRS Duration
Hide Description The QRS interval represents the time it takes for depolarization of the ventricles and was calculated from electrocardiogram (ECG) data. Each participant had triplicate QRS intervals measured at each timepoint and the average was calculated for each patient at each timepoint. For each timepoint, a participant's corresponding baseline QRS interval was subtracted from the average QRS intervals to create a baseline-adjusted average QRS interval.
Time Frame Cycle 1 Day 1, pre-dose (Baseline); Cycle 1 Day 1, 15 and 60 minutes post-dose; Cycle 1 Day 8; and Cycle 3 Day 1, 15 minutes pre-dose and 15 and 60 minutes post-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
ECG−Evaluable population; N indicates the ECG−evaluable population with available data at each time point.
Arm/Group Title T-DM1
Hide Arm/Group Description:
Trastuzumab emtansine (T-DM1) was administered to participants by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
Overall Number of Participants Analyzed 51
Mean (Standard Deviation)
Unit of Measure: milliseconds
Cycle 1 Day 1, 15 minutes post-dose [N=44] 1.2  (3.1)
Cycle 1 Day 1, 60 minutes post-dose [N=45] 0.4  (3.0)
Cycle 1 Day 8 [N=43] 1.1  (4.8)
Cycle 3 Day 1, 15 minutes pre-dose [N=35] 0.5  (4.5)
Cycle 3 Day 1, 15 minutes post-dose [N=37] 1.9  (4.0)
Cycle 3 Day 1, 60 minutes post-dose [N=37] 1.5  (3.8)
6.Secondary Outcome
Title Change From Baseline in Heart Rate
Hide Description [Not Specified]
Time Frame Cycle 1 Day 1, pre-dose (Baseline); Cycle 1 Day 1, 15 and 60 minutes post-dose; Cycle 1 Day 8; and Cycle 3 Day 1, 15 minutes pre-dose and 15 and 60 minutes post-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
ECG−evaluable population; N indicates the ECG−evaluable population with available data at each time point.
Arm/Group Title T-DM1
Hide Arm/Group Description:
Trastuzumab emtansine (T-DM1) was administered to participants by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
Overall Number of Participants Analyzed 51
Mean (Standard Deviation)
Unit of Measure: beats per minute
Cycle 1 Day 1, 15 minutes post-dose [N=44] 2.9  (8.3)
Cycle 1 Day 1, 60 minutes post-dose [N=45] 4.4  (7.9)
Cycle 1 Day 8 [N=43] 5.4  (8.8)
Cycle 3 Day 1, 15 minutes pre-dose [N=35] 4.1  (7.9)
Cycle 3 Day 1, 15 minutes post-dose [N=37] 0.8  (7.6)
Cycle 3 Day 1, 60 minutes post-dose [N=37] 2.4  (7.8)
7.Secondary Outcome
Title Percentage of Participants Within Each Absolute QTc Interval Category
Hide Description The corrected QT interval was calculated using Fridericia's correction (QTcF) and using Bazett's correction (QTcB) from electrocardiogram (ECG) data. Each participant had triplicate QTc intervals measured at each timepoint and the average was calculated for each patient at each timepoint. QTc interval categories are based off International Conference on Harmonisation (ICH) Tripartite Guideline E14.
Time Frame Cycle 1 Day 1, 15 and 60 minutes post-dose; Cycle 1 Day 8; and Cycle 3 Day 1, 15 minutes pre-dose and 15 and 60 minutes post-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
The number of participants analyzed for each QTc interval category represents the total treated population. N indicates the ECG−evaluable population with available data at each time point.
Arm/Group Title Average QTc Interval ≤ 450 ms Average QTc Interval > 450 to ≤ 480 ms Average QTc Interval > 480 to ≤ 500 ms Average QTc Interval > 500 ms
Hide Arm/Group Description:
Participants with an average QTc interval less than or equal to 450 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
Participants with an average QTc interval greater than 450 and less than or equal to 480 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
Participants with an average QTc interval greater than 480 and less than or equal to 500 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
Participants with an average QTc interval greater than 500 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
Overall Number of Participants Analyzed 51 51 51 51
Measure Type: Number
Unit of Measure: percentage of participants
QTcF: Cycle 1, Day 1, 15 minutes post-dose [N=44] 100 0 0 0
QTcF: Cycle 1, Day 1, 60 minutes post-dose [N=45] 100 0 0 0
QTcF: Cycle 1, Day 8 [N=43] 100 0 0 0
QTcF: Cycle 3, Day 1, 15 minutes pre−dose [N=35] 97.1 2.9 0 0
QTcF: Cycle 3, Day 1, 15 minutes post−dose [N=37] 94.6 5.4 0 0
QTcF: Cycle 3, Day 1, 60 minutes post−dose [N=37] 97.3 2.7 0 0
QTcB: Cycle 1, Day 1, 15 minutes post-dose [N=44] 79.5 20.5 0 0
QTcB: Cycle 1, Day 1, 60 minutes post-dose [N=45] 73.3 26.7 0 0
QTcB: Cycle 1, Day 8 [N=43] 79.1 20.9 0 0
QTcB: Cycle 3, Day 1, 15 minutes pre−dose [N=35] 82.9 17.1 0 0
QTcB: Cycle 3, Day 1, 15 minutes post−dose [N=37] 70.3 29.7 0 0
QTcB: Cycle 3, Day 1, 60 minutes post−dose [N=37] 70.3 29.7 0 0
8.Secondary Outcome
Title Percentage of Participants Within Each Baseline-adjusted QTc Interval Category
Hide Description

The corrected QT interval was calculated using Fridericia's correction (QTcF) and using Bazett's correction (QTcB) from electrocardiogram (ECG) data. Each participant had triplicate QTc intervals measured at each timepoint and the average was calculated for each patient at each timepoint. For each timepoint, a participant's corresponding baseline QTc interval was subtracted from the average QTc intervals to create a baseline-adjusted average QTc interval.

QTc interval categories are based off International Conference on Harmonisation (ICH) Tripartite Guideline E14.

Time Frame Cycle 1 Day 1, pre-dose (Baseline); Cycle 1 Day 1, 15 and 60 minutes post-dose; Cycle 1 Day 8; and Cycle 3 Day 1, 15 minutes pre-dose and 15 and 60 minutes post-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
The number of participants analyzed for each QTc interval category represents the total treated population. N indicates the ECG−evaluable population with available data at each time point.
Arm/Group Title Baseline-adjusted QTc Interval ≤ 30 ms Baseline-adjusted QTc Interval > 30 to ≤ 60 ms Baseline-adjusted QTc Interval > 60 ms
Hide Arm/Group Description:
Participants with an average Baseline-adjusted QTc interval less than or equal to 30 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
Participants with an average Baseline-adjusted QTc interval greater than 30 and less than or equal to 60 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
Participants with an average Baseline-adjusted QTc interval greater than 60 ms who received trastuzumab emtansine (T-DM1) by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
Overall Number of Participants Analyzed 51 51 51
Measure Type: Number
Unit of Measure: percentage of participants
QTcF: Cycle 1, Day 1, 15 minutes post-dose [N=44] 100 0 0
QTcF: Cycle 1, Day 1, 60 minutes post-dose [N=45] 100 0 0
QTcF: Cycle 1, Day 8 [N=43] 100 0 0
QTcF: Cycle 3, Day 1, 15 minutes pre−dose [N=35] 100 0 0
QTcF: Cycle 3, Day 1, 15 minutes post−dose [N=37] 100 0 0
QTcF: Cycle 3, Day 1, 60 minutes post−dose [N=37] 100 0 0
QTcB: Cycle 1, Day 1, 15 minutes post-dose [N=44] 100 0 0
QTcB: Cycle 1, Day 1, 60 minutes post-dose [N=45] 100 0 0
QTcB: Cycle 1, Day 8 [N=43] 100 0 0
QTcB: Cycle 3, Day 1, 15 minutes pre−dose [N=35] 94.3 5.7 0
QTcB: Cycle 3, Day 1, 15 minutes post−dose [N=37] 94.6 5.4 0
QTcB: Cycle 3, Day 1, 60 minutes post−dose [N=37] 97.3 2.7 0
9.Secondary Outcome
Title Percentage of Participants With New Abnormal U Waves
Hide Description The incidence of abnormal U-wave changes from baseline was determined based on centrally read electrocardiogram (ECG) tracings comparing each of the three triplicate readings from the post baseline ECG time points to the baseline ECG reading. At each time point, if at least one of the three triplicate readings was abnormal, the participant was counted as abnormal for that ECG timepoint as follows: a large U wave, inverted U wave, or T-U fusion compared with baseline was considered an abnormal significant change from baseline.
Time Frame Cycle 1 Day 1, pre-dose (Baseline); Cycle 1 Day 1, 15 and 60 minutes post-dose; Cycle 1 Day 8; and Cycle 3 Day 1, 15 minutes pre-dose and 15 and 60 minutes post-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
ECG−evaluable population; N indicates the ECG−evaluable population with available data at each time point.
Arm/Group Title T-DM1
Hide Arm/Group Description:
Trastuzumab emtansine (T-DM1) was administered to participants by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
Overall Number of Participants Analyzed 51
Measure Type: Number
Unit of Measure: percentage of participants
Cycle 1, Day 1, 15 minutes post-dose [N=44] 0
Cycle 1, Day 1, 60 minutes post-dose [N=45] 0
Cycle 1, Day 8 [N=43] 0
Cycle 3, Day 1, 15 minutes pre−dose [N=35] 0
Cycle 3, Day 1, 15 minutes post−dose [N=36] 0
Cycle 3, Day 1, 60 minutes post−dose [N=37] 0
10.Secondary Outcome
Title Percentage of Participants With New Abnormal T Waves
Hide Description The incidence of abnormal T-wave changes from baseline was determined based on centrally read electrocardiogram (ECG) tracings comparing each of the three triplicate readings from the post baseline ECG time points to the baseline ECG reading. At each time point, if at least one of the three triplicate readings was abnormal, the participant was counted as abnormal for that ECG timepoint as follows: an inverted T, flat T, or biphasic T compared with baseline was considered an abnormal significant change from baseline. Additionally, nonspecific T-wave changes from baseline were considered as abnormal nonsignificant changes from baseline. T-wave changes from baseline due to ventricular conduction or left ventricular hypertrophy strain were considered not evaluable. C=Cycle; D=Day.
Time Frame Cycle 1 Day 1, pre-dose (Baseline); Cycle 1 Day 1, 15 and 60 minutes post-dose; Cycle 1 Day 8; and Cycle 3 Day 1, 15 minutes pre-dose and 15 and 60 minutes post-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
ECG−Evaluable population; N indicates the ECG−evaluable population with available data at each time point.
Arm/Group Title T-DM1
Hide Arm/Group Description:
Trastuzumab emtansine (T-DM1) was administered to participants by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
Overall Number of Participants Analyzed 51
Measure Type: Number
Unit of Measure: percentage of participants
Significant: C1D1, 15 minutes post-dose [N=44] 0
Significant: C1D1, 60 minutes post-dose [N=45] 0
Significant: C1D8 [N=43] 2.3
Significant: C3D1, 15 minutes pre−dose [N=35] 0
Significant: C3D1, 15 minutes post−dose [N=36] 0
Significant: C3D1, 60 minutes post−dose [N=37] 0
Non-Significant: C1D1, 15 minutes post-dose [N=44] 13.6
Non-Significant: C1D1, 60 minutes post-dose [N=45] 11.1
Non-Significant: C1D8 [N=43] 20.9
Non-Significant: C3D1, 15 minutes pre−dose [N=35] 17.1
Non-Significant: C3D1, 15 minutes post−dose [N=36] 13.9
Non-Significant: C3D1, 60 minutes post−dose [N=37] 27.0
11.Secondary Outcome
Title Percentage of Participants With an Objective Response During the Single-agent Trastuzumab Emtansine Treatment Period
Hide Description

Objective response was defined as a complete response (CR) or partial response (PR) determined on two consecutive assessments conducted by the investigator ≥ 4 weeks apart. Responses were assessed by physical examination and imaged-based evaluation using a modified version of the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0:

CR—the disappearance of all target lesions and the disappearance of all nontarget lesions and normalization of tumor marker level and no new lesions.

PR—either the disappearance of all target lesions with persistence of one or more nontarget lesion(s) and/or the maintenance of tumor marker level above the normal limits, or, at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter with no new lesions or unequivocal progression of existing nontarget lesions.

Time Frame Tumor assessments were performed after every three cycles until study termination or progressive disease (up to a maximum of one year).
Hide Outcome Measure Data
Hide Analysis Population Description
The efficacy-evaluable population was defined as patients who received at least one dose of study drug. Patients with missing or no post-baseline response assessments were classified as non-responders.
Arm/Group Title T-DM1
Hide Arm/Group Description:

Trastuzumab emtansine (T-DM1) was administered to participants by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.

Participants who met criteria for ongoing clinical benefit were allowed to continue study treatment in the absence of disease progression or unacceptable toxicity for up to 1 year.

Overall Number of Participants Analyzed 51
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
25.5
(15.2 to 38.5)
12.Secondary Outcome
Title Duration of Objective Response Based on Investigator Assessment During the Single-agent Trastuzumab Emtansine Treatment Period
Hide Description

In patients with an objective response during the single-agent trastuzumab emtansine treatment period, duration of response was defined as the time from the first documented objective response to the time of first documented disease progression or death, whichever occurred first. Progressive disease was defined as either at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study with an absolute increase of at least 5 mm, or the appearance of one or more new lesions, or the unequivocal progression of existing nontarget lesions.

If a patient did not die or experience disease progression before the end of the study, duration of response was censored at the day of the last tumor assessment when the patient was known to be progression free.

Time Frame Time from the first documented objective response to the time of first documented disease progression or death, up to a maximum time period of one year.
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy evaluable patients who achieved an objective response.
Arm/Group Title T-DM1
Hide Arm/Group Description:

Trastuzumab emtansine (T-DM1) was administered to participants by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.

Participants who met criteria for ongoing clinical benefit were allowed to continue study treatment in the absence of disease progression or unacceptable toxicity for up to 1 year.

Overall Number of Participants Analyzed 13
Median (95% Confidence Interval)
Unit of Measure: months
9.3 [1] 
(4.7 to NA)
[1]
Upper limit of the confidence not estimable due to the low number of patients with an event (7).
13.Secondary Outcome
Title Progression-free Survival During the Single-agent Trastuzumab Emtansine Treatment Period
Hide Description Progression-free survival (PFS) was defined as the time from the first day of study treatment (Day 1) to first documented disease progression or death, whichever occurred first. If a patient did not experience disease progression or die, PFS was censored at the day of the last tumor assessment that a patient was known to be progression free.
Time Frame From the first day of study treatment to the first documented disease progression or death, up to a maximum time period of one year.
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy evaluable patients.
Arm/Group Title T-DM1
Hide Arm/Group Description:

Trastuzumab emtansine (T-DM1) was administered to participants by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.

Participants who met criteria for ongoing clinical benefit were allowed to continue study treatment in the absence of disease progression or unacceptable toxicity for up to 1 year.

Overall Number of Participants Analyzed 51
Median (95% Confidence Interval)
Unit of Measure: months
4.3
(4.0 to 6.7)
14.Secondary Outcome
Title Percentage of Participants With Clinical Benefit During the Single-agent Trastuzumab Emtansine Treatment Period
Hide Description

Participants were considered to have experienced clinical benefit if they had an objective response or maintained stable disease for at least 6 months from start of study treatment. Objective response was defined as a complete or partial response determined on two consecutive tumor assessments at least 4 weeks apart based on a modified version of RECIST.

Stable disease was defined as neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum longest diameter since the treatment started and no new lesions or unequivocal progression of existing nontarget lesions.

Time Frame Tumor assessments were performed after every three cycles until study termination or progressive disease (up to a maximum of one year).
Hide Outcome Measure Data
Hide Analysis Population Description
The efficacy-evaluable population was defined as patients who received at least one dose of study drug.
Arm/Group Title T-DM1
Hide Arm/Group Description:

Trastuzumab emtansine (T-DM1) was administered to participants by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.

Participants who met criteria for ongoing clinical benefit were allowed to continue study treatment in the absence of disease progression or unacceptable toxicity for up to 1 year.

Overall Number of Participants Analyzed 51
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
39.2
(25.8 to 53.1)
15.Secondary Outcome
Title Number of Participants With Adverse Events (AEs)
Hide Description

An serious AE is any AE that is fatal, life threatening, requires or prolongs inpatient hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect in a neonate/infant born to a mother exposed to the investigational product(s), or is considered a significant medical event by the investigator (e.g., may jeopardize the patient or may require medical/surgical intervention to prevent one of the outcomes listed above).

The severity of each AE was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0, or as follows: Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Very severe; Grade 5 = Death related to AE.

Time Frame From first dose until 30 days after last dose (up to 1 year).
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Safety-Evaluable Patients (i.e., the treated population).
Arm/Group Title T-DM1 T-DM1 + Pertuzumab
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Trastuzumab emtansine (T-DM1) was administered to participants by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
Participants who received combined pertuzumab and trastuzumab emtansine. Pertuzumab was administered after trastuzumab emtansine by IV infusion at a loading dose of 840 mg on Day 1, followed by 420 mg IV infusion every 3 weeks in subsequent cycles.
Overall Number of Participants Analyzed 51 20
Measure Type: Number
Unit of Measure: participants
Any adverse event 51 18
Grade ≥ 3 adverse events 17 12
Serious adverse events 4 5
Adverse events leading to treatment discontinuatio 2 5
Deaths 0 0
16.Secondary Outcome
Title Number of Participants With Decreased Ejection Fraction
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Left ventricular ejection fraction (LVEF) was assessed on the basis of local assessments of echocardiogram or multigated acquisition scan (MUGA) data. A decrease in LVEF is defined as a decrease from Baseline of greater than or equal to 15%.

Grade 3 LVEF is an ejection fraction between 20 and 40%.

Time Frame Assessed at Baseline and after every 3 cycles, up to 1 year.
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Hide Analysis Population Description
Safety-Evaluable Patients (i.e., the treated population).
Arm/Group Title T-DM1 T-DM1 + Pertuzumab
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Trastuzumab emtansine (T-DM1) was administered to participants by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
Participants who received combined pertuzumab and trastuzumab emtansine. Pertuzumab was administered after trastuzumab emtansine by IV infusion at a loading dose of 840 mg on Day 1, followed by 420 mg IV infusion every 3 weeks in subsequent cycles.
Overall Number of Participants Analyzed 51 20
Measure Type: Number
Unit of Measure: participants
Grade 3 1 0
Overall 1 1
17.Secondary Outcome
Title Maximum Observed Serum Concentration of T-DM1 and Total Trastuzumab
Hide Description Serum samples were quantitated for T-DM1 (DM1 conjugated to trastuzumab) levels in a validated assay using an indirect sandwich enzyme-linked immunosorbent assay (ELISA). The minimum quantifiable concentration in human serum was 40 ng/mL. Serum samples were assayed for total trastuzumab (conjugated and unconjugated T-DM1) in a validated assay using an indirect sandwich ELISA method; the minimum quantifiable concentration in human serum was 40 ng/mL.
Time Frame Blood samples were collected prior to dosing, 15 and 60 minutes after the end of infusion, and anytime on Days 8 and 15 in Cycles 1 and 3, and pre-dose in Cycle 4.
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Hide Analysis Population Description
Pharmacokinetic (PK)-evaluable patients were defined as patients who had adequate concentration−time data to estimate at least one PK parameter. "N" refers to the number of PK-evaluable patients in that cycle.
Arm/Group Title Single-Agent T-DM1 Treatment
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Trastuzumab emtansine (T-DM1) was administered to participants by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
Overall Number of Participants Analyzed 51
Mean (Standard Deviation)
Unit of Measure: μg/mL
Cycle 1: T-DM1 [N=51] 75.6  (21.9)
Cycle 1: Total trastuzumab [N=51] 95.9  (32.3)
Cycle 3: T-Dm1 [N=47] 80.7  (18.1)
Cycle 3: Total trastuzumab [N=47] 98.6  (26.1)
18.Secondary Outcome
Title Area Under the Concentration-time Curve From Time 0 to Time of Last Measurable Concentration for T-DM1 and Total Trastuzumab
Hide Description Area under the serum concentration−time curve from Time zero to time of last measurable concentration (AUClast) for T-DM1 (conjugated trastuzumab) and Total Trastuzumab (conjugated and unconjugated T-DM1) at Cycle 1 and Cycle 3.
Time Frame Blood samples were collected prior to T-DM1 dosing, 15 and 60 minutes after the end of infusion, and anytime on Days 8 and 15 in Cycles 1 and 3, and pre-dose in Cycle 4.
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Hide Analysis Population Description
PK-evaluable patients were defined as patients who had adequate concentration−time data to estimate at least one PK parameter. "N" refers to the number of PK-evaluable patients in that cycle.
Arm/Group Title Single-Agent T-DM1 Treatment
Hide Arm/Group Description:
Trastuzumab emtansine (T-DM1) was administered to participants by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
Overall Number of Participants Analyzed 51
Mean (Standard Deviation)
Unit of Measure: μg * day/mL
Cycle 1: T-DM1 [N=51] 418  (121)
Cycle 1: Total trastuzumab [N=51] 929  (564)
Cycle 3: T-Dm1 [N=47] 475  (150)
Cycle 3: Total trastuzumab [N=47] 958  (394)
19.Secondary Outcome
Title Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity for T-DM1 and Total Trastuzumab
Hide Description Area under the serum concentration−time curve from Time zero extrapolated to infinity (AUCinf) for T-DM1 (conjugated trastuzumab) and total trastuzumab (conjugated and unconjugated T-DM1) at Cycle 1.
Time Frame Blood samples were collected prior to T-DM1 dosing, 15 and 60 minutes after the end of infusion, and anytime on Days 8 and 15 in Cycle 1.
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Hide Analysis Population Description
PK-evaluable patients were defined as patients who had adequate concentration−time data to estimate at least one PK parameter. "N" refers to the number of PK-evaluable patients in that cycle.
Arm/Group Title Single-Agent T-DM1 Treatment
Hide Arm/Group Description:
Trastuzumab emtansine (T-DM1) was administered to participants by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
Overall Number of Participants Analyzed 51
Mean (Standard Deviation)
Unit of Measure: μg * day/mL
T-DM1 431  (126)
Total trastuzumab 1420  (1390)
20.Secondary Outcome
Title Terminal Half-life for T-DM1 and Total Trastuzumab
Hide Description [Not Specified]
Time Frame Blood samples were collected prior to T-DM1 dosing, 15 and 60 minutes after the end of infusion, and anytime on Days 8 and 15 in Cycles 1 and 3, and pre-dose in Cycle 4.
Hide Outcome Measure Data
Hide Analysis Population Description
PK-evaluable patients were defined as patients who had adequate concentration−time data to estimate at least one PK parameter. "N" refers to the number of PK-evaluable patients in that cycle.
Arm/Group Title Single-Agent T-DM1 Treatment
Hide Arm/Group Description:
Trastuzumab emtansine (T-DM1) was administered to participants by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
Overall Number of Participants Analyzed 51
Mean (Standard Deviation)
Unit of Measure: days
Cycle 1: T-DM1 [N=51] 4.02  (0.938)
Cycle 1: Total trastuzumab [N=51] 10.3  (6.81)
Cycle 3: T-Dm1 [N=47] 4.46  (0.926)
Cycle 3: Total trastuzumab [N=47] 12.0  (6.24)
21.Secondary Outcome
Title Clearance T-DM1 and Total Trastuzumab
Hide Description [Not Specified]
Time Frame Blood samples were collected prior to T-DM1 dosing, 15 and 60 minutes after the end of infusion, and anytime on Days 8 and 15 in Cycles 1 and 3, and pre-dose in Cycle 4.
Hide Outcome Measure Data
Hide Analysis Population Description
PK-evaluable patients were defined as patients who had adequate concentration−time data to estimate at least one PK parameter. "N" refers to the number of PK-evaluable patients in that cycle.
Arm/Group Title Single-Agent T-DM1 Treatment
Hide Arm/Group Description:
Trastuzumab emtansine (T-DM1) was administered to participants by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
Overall Number of Participants Analyzed 51
Mean (Standard Deviation)
Unit of Measure: mL/day/kg
Cycle 1: T-DM1 [N=51] 9.17  (3.03)
Cycle 1: Total trastuzumab [N=51] 4.21  (2.43)
Cycle 3: T-Dm1 [N=47] 7.91  (3.30)
Cycle 3: Total trastuzumab [N=47] 3.12  (1.71)
22.Secondary Outcome
Title Volume of Distribution at Steady State for T-DM1 and Total Trastuzumab
Hide Description [Not Specified]
Time Frame Blood samples were collected prior to T-DM1 dosing, 15 and 60 minutes after the end of infusion, and anytime on Days 8 and 15 in Cycles 1 and 3, and pre-dose in Cycle 4.
Hide Outcome Measure Data
Hide Analysis Population Description
PK-evaluable patients were defined as patients who had adequate concentration−time data to estimate at least one PK parameter. "N" refers to the number of PK-evaluable patients in that cycle.
Arm/Group Title Single-Agent T-DM1 Treatment
Hide Arm/Group Description:
Trastuzumab emtansine (T-DM1) was administered to participants by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
Overall Number of Participants Analyzed 51
Mean (Standard Deviation)
Unit of Measure: mL/kg
Cycle 1: T-DM1 [N=51] 41.2  (24.5)
Cycle 1: Total trastuzumab [N=51] 41.9  (16.2)
Cycle 3: T-Dm1 [N=47] 43.6  (40.7)
Cycle 3: Total trastuzumab [N=47] 43.7  (15.4)
23.Secondary Outcome
Title Number of Participants With Anti-therapeutic Antibodies (ATAs) to Trastuzumab Emtansine
Hide Description The number of participants with anti-T-DM1 antibodies was assessed using a validated bridging antibody enzyme-linked immunosorbent assay (ELISA).
Time Frame Blood samples were collected prior to T-DM1 dosing, 15 and 60 minutes after the end of infusion, and anytime on Days 8 and 15 in Cycles 1 and 3, and pre-dose in Cycle 4.
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Hide Analysis Population Description
Evaluable patients, defined as patients who had at least one ATA measurement available for analysis at Baseline (pre-dose in Cycle 1) and post-baseline.
Arm/Group Title Single-Agent T-DM1 Treatment
Hide Arm/Group Description:
Trastuzumab emtansine (T-DM1) was administered to participants by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg.
Overall Number of Participants Analyzed 47
Measure Type: Number
Unit of Measure: participants
Pre-dose (Baseline) 2
Post-dose 0
Time Frame 1 year
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Single-Agent T-DM1 Treatment T-DM1 + Pertuzumab
Hide Arm/Group Description Trastuzumab emtansine (T-DM1) was administered to participants by intravenous (IV) infusion on Day 1 of every 3 week cycle at a dose of 3.6 mg/kg. Participants who received combined pertuzumab and trastuzumab emtansine. Pertuzumab was administered after trastuzumab emtansine by IV infusion at a loading dose of 840 mg on Day 1, followed by 420 mg IV infusion every 3 weeks in subsequent cycles.
All-Cause Mortality
Single-Agent T-DM1 Treatment T-DM1 + Pertuzumab
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Single-Agent T-DM1 Treatment T-DM1 + Pertuzumab
Affected / at Risk (%) Affected / at Risk (%)
Total   4/51 (7.84%)   5/20 (25.00%) 
Blood and lymphatic system disorders     
Thrombocytopenia  1  2/51 (3.92%)  1/20 (5.00%) 
Anaemia  1  0/51 (0.00%)  2/20 (10.00%) 
Cardiac disorders     
Cardiac arrest  1  0/51 (0.00%)  1/20 (5.00%) 
Gastrointestinal disorders     
Gastrointestinal haemorrhage  1  0/51 (0.00%)  1/20 (5.00%) 
General disorders     
Generalised oedema  1  1/51 (1.96%)  0/20 (0.00%) 
Investigations     
Aspartate aminotransferase increased  1  0/51 (0.00%)  1/20 (5.00%) 
Metabolism and nutrition disorders     
Hypokalaemia  1  0/51 (0.00%)  1/20 (5.00%) 
Nervous system disorders     
Convulsion  1  1/51 (1.96%)  0/20 (0.00%) 
Renal and urinary disorders     
Renal failure  1  1/51 (1.96%)  0/20 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1  1/51 (1.96%)  0/20 (0.00%) 
Skin and subcutaneous tissue disorders     
Skin haemorrhage  1  0/51 (0.00%)  1/20 (5.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (13.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Single-Agent T-DM1 Treatment T-DM1 + Pertuzumab
Affected / at Risk (%) Affected / at Risk (%)
Total   51/51 (100.00%)   18/20 (90.00%) 
Blood and lymphatic system disorders     
Anaemia  1  7/51 (13.73%)  6/20 (30.00%) 
Thrombocytopenia  1  17/51 (33.33%)  2/20 (10.00%) 
Neutropenia  1  3/51 (5.88%)  1/20 (5.00%) 
Leukopenia  1  4/51 (7.84%)  0/20 (0.00%) 
Lymphopenia  1  3/51 (5.88%)  0/20 (0.00%) 
Cardiac disorders     
Cardiac flutter  1  0/51 (0.00%)  1/20 (5.00%) 
Tachycardia  1  4/51 (7.84%)  0/20 (0.00%) 
Eye disorders     
Conjunctivitis  1  0/51 (0.00%)  1/20 (5.00%) 
Diplopia  1  0/51 (0.00%)  1/20 (5.00%) 
Vision blurred  1  6/51 (11.76%)  1/20 (5.00%) 
Gastrointestinal disorders     
Vomiting  1  16/51 (31.37%)  4/20 (20.00%) 
Diarrhoea  1  4/51 (7.84%)  3/20 (15.00%) 
Nausea  1  33/51 (64.71%)  3/20 (15.00%) 
Abdominal pain  1  4/51 (7.84%)  2/20 (10.00%) 
Dry mouth  1  25/51 (49.02%)  2/20 (10.00%) 
Abdominal distension  1  1/51 (1.96%)  1/20 (5.00%) 
Abdominal pain lower  1  1/51 (1.96%)  1/20 (5.00%) 
Abdominal pain upper  1  3/51 (5.88%)  1/20 (5.00%) 
Constipation  1  12/51 (23.53%)  1/20 (5.00%) 
Diverticulum intestinal  1  0/51 (0.00%)  1/20 (5.00%) 
Dysphagia  1  1/51 (1.96%)  1/20 (5.00%) 
Faecal incontinence  1  0/51 (0.00%)  1/20 (5.00%) 
Food poisoning  1  0/51 (0.00%)  1/20 (5.00%) 
Gastritis  1  1/51 (1.96%)  1/20 (5.00%) 
Haematemesis  1  0/51 (0.00%)  1/20 (5.00%) 
Stomatitis  1  3/51 (5.88%)  1/20 (5.00%) 
Gastrooesophageal reflux disease  1  3/51 (5.88%)  0/20 (0.00%) 
General disorders     
Fatigue  1  33/51 (64.71%)  4/20 (20.00%) 
Pain  1  4/51 (7.84%)  4/20 (20.00%) 
Pyrexia  1  12/51 (23.53%)  2/20 (10.00%) 
Catheter site erythema  1  0/51 (0.00%)  1/20 (5.00%) 
Chest discomfort  1  2/51 (3.92%)  1/20 (5.00%) 
Chest pain  1  1/51 (1.96%)  1/20 (5.00%) 
Drug effect increased  1  0/51 (0.00%)  1/20 (5.00%) 
Medical device complication  1  0/51 (0.00%)  1/20 (5.00%) 
Oedema peripheral  1  1/51 (1.96%)  1/20 (5.00%) 
Thirst  1  1/51 (1.96%)  1/20 (5.00%) 
Chills  1  11/51 (21.57%)  0/20 (0.00%) 
Asthenia  1  3/51 (5.88%)  0/20 (0.00%) 
Gait disturbance  1  3/51 (5.88%)  0/20 (0.00%) 
Hepatobiliary disorders     
Bile duct stenosis  1  0/51 (0.00%)  1/20 (5.00%) 
Biliary dilatation  1  0/51 (0.00%)  1/20 (5.00%) 
Hepatic cirrhosis  1  0/51 (0.00%)  1/20 (5.00%) 
Infections and infestations     
Upper respiratory tract infection  1  9/51 (17.65%)  3/20 (15.00%) 
Catheter site cellulitis  1  0/51 (0.00%)  1/20 (5.00%) 
Cellulitis  1  1/51 (1.96%)  1/20 (5.00%) 
Conjunctivitis infective  1  0/51 (0.00%)  1/20 (5.00%) 
Device related infection  1  0/51 (0.00%)  1/20 (5.00%) 
Urinary tract infection  1  9/51 (17.65%)  0/20 (0.00%) 
Herpes zoster  1  3/51 (5.88%)  0/20 (0.00%) 
Injury, poisoning and procedural complications     
Contusion  1  3/51 (5.88%)  1/20 (5.00%) 
Gastroenteritis radiation  1  0/51 (0.00%)  1/20 (5.00%) 
Infusion related reaction  1  2/51 (3.92%)  1/20 (5.00%) 
Investigations     
Aspartate aminotransferase increased  1  17/51 (33.33%)  4/20 (20.00%) 
Blood alkaline phosphatase increased  1  4/51 (7.84%)  4/20 (20.00%) 
Alanine aminotransferase increased  1  7/51 (13.73%)  2/20 (10.00%) 
Weight decreased  1  5/51 (9.80%)  2/20 (10.00%) 
Ejection fraction decreased  1  1/51 (1.96%)  1/20 (5.00%) 
Haemoglobin decreased  1  1/51 (1.96%)  1/20 (5.00%) 
International normalised ratio increased  1  0/51 (0.00%)  1/20 (5.00%) 
Weight increased  1  2/51 (3.92%)  1/20 (5.00%) 
Blood lactate dehydrogenase increased  1  8/51 (15.69%)  0/20 (0.00%) 
Metabolism and nutrition disorders     
Decreased appetite  1  12/51 (23.53%)  3/20 (15.00%) 
Hypokalaemia  1  12/51 (23.53%)  2/20 (10.00%) 
Hypercalcaemia  1  0/51 (0.00%)  1/20 (5.00%) 
Hypoalbuminaemia  1  2/51 (3.92%)  1/20 (5.00%) 
Hypoglycaemia  1  2/51 (3.92%)  1/20 (5.00%) 
Hyperglycaemia  1  5/51 (9.80%)  0/20 (0.00%) 
Hypomagnesaemia  1  4/51 (7.84%)  0/20 (0.00%) 
Musculoskeletal and connective tissue disorders     
Bone pain  1  2/51 (3.92%)  3/20 (15.00%) 
Back pain  1  4/51 (7.84%)  2/20 (10.00%) 
Muscle spasms  1  1/51 (1.96%)  2/20 (10.00%) 
Musculoskeletal pain  1  6/51 (11.76%)  2/20 (10.00%) 
Arthralgia  1  9/51 (17.65%)  1/20 (5.00%) 
Flank pain  1  2/51 (3.92%)  1/20 (5.00%) 
Muscle twitching  1  0/51 (0.00%)  1/20 (5.00%) 
Muscular weakness  1  2/51 (3.92%)  1/20 (5.00%) 
Musculoskeletal chest pain  1  4/51 (7.84%)  1/20 (5.00%) 
Musculoskeletal discomfort  1  0/51 (0.00%)  1/20 (5.00%) 
Musculoskeletal stiffness  1  2/51 (3.92%)  1/20 (5.00%) 
Myalgia  1  3/51 (5.88%)  1/20 (5.00%) 
Pain in extremity  1  5/51 (9.80%)  0/20 (0.00%) 
Neck pain  1  4/51 (7.84%)  0/20 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Benign neoplasm of thyroid gland  1  0/51 (0.00%)  1/20 (5.00%) 
Metastases to central nervous system  1  0/51 (0.00%)  1/20 (5.00%) 
Tumour haemorrhage  1  1/51 (1.96%)  1/20 (5.00%) 
Nervous system disorders     
Dizziness  1  5/51 (9.80%)  2/20 (10.00%) 
Headache  1  11/51 (21.57%)  2/20 (10.00%) 
Ataxia  1  1/51 (1.96%)  1/20 (5.00%) 
Central nervous system lesion  1  0/51 (0.00%)  1/20 (5.00%) 
Facial paresis  1  0/51 (0.00%)  1/20 (5.00%) 
Memory impairment  1  1/51 (1.96%)  1/20 (5.00%) 
Migraine  1  0/51 (0.00%)  1/20 (5.00%) 
Neuropathy peripheral  1  6/51 (11.76%)  1/20 (5.00%) 
Restless legs syndrome  1  1/51 (1.96%)  1/20 (5.00%) 
Sedation  1  1/51 (1.96%)  1/20 (5.00%) 
Dysgeusia  1  6/51 (11.76%)  0/20 (0.00%) 
Paraesthesia  1  5/51 (9.80%)  0/20 (0.00%) 
Hypoaesthesia  1  4/51 (7.84%)  0/20 (0.00%) 
Psychiatric disorders     
Depression  1  3/51 (5.88%)  3/20 (15.00%) 
Anxiety  1  3/51 (5.88%)  2/20 (10.00%) 
Insomnia  1  8/51 (15.69%)  2/20 (10.00%) 
Food aversion  1  0/51 (0.00%)  1/20 (5.00%) 
Renal and urinary disorders     
Micturition disorder  1  0/51 (0.00%)  1/20 (5.00%) 
Proteinuria  1  6/51 (11.76%)  0/20 (0.00%) 
Reproductive system and breast disorders     
Vaginal haemorrhage  1  3/51 (5.88%)  1/20 (5.00%) 
Respiratory, thoracic and mediastinal disorders     
Epistaxis  1  10/51 (19.61%)  3/20 (15.00%) 
Cough  1  8/51 (15.69%)  2/20 (10.00%) 
Dyspnoea  1  7/51 (13.73%)  1/20 (5.00%) 
Dyspnoea exertional  1  1/51 (1.96%)  1/20 (5.00%) 
Oropharyngeal pain  1  4/51 (7.84%)  1/20 (5.00%) 
Skin and subcutaneous tissue disorders     
Dermatitis acneiform  1  1/51 (1.96%)  1/20 (5.00%) 
Papule  1  0/51 (0.00%)  1/20 (5.00%) 
Pruritus  1  1/51 (1.96%)  1/20 (5.00%) 
Rash  1  5/51 (9.80%)  1/20 (5.00%) 
Subcutaneous nodule  1  0/51 (0.00%)  1/20 (5.00%) 
Blister  1  4/51 (7.84%)  0/20 (0.00%) 
Nail disorder  1  3/51 (5.88%)  0/20 (0.00%) 
Vascular disorders     
Flushing  1  1/51 (1.96%)  1/20 (5.00%) 
Hypertension  1  7/51 (13.73%)  0/20 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (13.0)
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 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
Name/Title: Medical Communications
Organization: Hoffman-LaRoche
Phone: 800-821-8590
Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT00943670     History of Changes
Other Study ID Numbers: TDM4688g
First Submitted: July 19, 2009
First Posted: July 22, 2009
Results First Submitted: March 12, 2013
Results First Posted: May 1, 2013
Last Update Posted: May 27, 2013