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A Study of Trastuzumab Emtansine (Trastuzumab-MCC-DM1) Administered Intravenously to Patients With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Metastatic Breast Cancer

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ClinicalTrials.gov Identifier: NCT00509769
Recruitment Status : Completed
First Posted : July 31, 2007
Results First Posted : April 2, 2013
Last Update Posted : April 2, 2013
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Metastatic Breast Cancer
Intervention Drug: Trastuzumab emtansine [Kadcyla]
Enrollment 112

Recruitment Details  
Pre-assignment Details  
Arm/Group Title Trastuzumab Emtansine 3.6 mg/kg
Hide Arm/Group Description Patients received trastuzumab emtansine 3.6 mg/kg intravenously on Day 1 of each 21 day cycle for a maximum of 1 year. The total dose was dependent on the patient's weight on Day 1 of each cycle.
Period Title: Overall Study
Started 112
Completed 21
Not Completed 91
Reason Not Completed
Progressive disease             77
Adverse Event             4
Patient’s decision             1
Physician Decision             8
Use of prohibited therapies during study             1
Arm/Group Title Trastuzumab Emtansine 3.6 mg/kg
Hide Arm/Group Description Patients received trastuzumab emtansine 3.6 mg/kg intravenously on Day 1 of each 21 day cycle for a maximum of 1 year. The total dose was dependent on the patient's weight on Day 1 of each cycle.
Overall Number of Baseline Participants 112
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 112 participants
55.0  (10.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 112 participants
Female
111
  99.1%
Male
1
   0.9%
1.Primary Outcome
Title Objective Response Assessed by the Independent Review Facility Using Response Evaluation Criteria in Solid Tumors (RECIST)
Hide Description Objective response was defined as a complete response (CR) or partial response (PR) determined on 2 consecutive occasions ≥ 4 weeks apart, using Response Evaluation Criteria in Solid Tumors (RECIST). CR: The disappearance of all target lesions and all non-target lesions, normalization of tumor marker level, and no new lesions. PR: Disappearance of all target lesions and persistence of ≥ 1 non-target lesions 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, and no new lesions or unequivocal progression of existing non-target lesions.
Time Frame Randomization until the analysis data cutoff-dates of 31 Jan 2009 (6 months after the last patient was enrolled in the study) and 25 Jun 2009 (approximately 12 months after the last patient was enrolled in the study, up to 23 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Efficacy evaluable population: All patients who received at least 1 dose of study drug and who underwent a baseline and at least 1 post-baseline tumor assessment or died while in the study from any cause within 30 days of the last dose of study drug.
Arm/Group Title Trastuzumab Emtansine 3.6 mg/kg
Hide Arm/Group Description:
Patients received trastuzumab emtansine 3.6 mg/kg intravenously on Day 1 of each 21 day cycle for a maximum of 1 year. The total dose was dependent on the patient's weight on Day 1 of each cycle.
Overall Number of Participants Analyzed 109
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of patients
Month 6 (n=109)
25.7
(17.9 to 34.5)
Month 12 (n=108)
26.9
(19.2 to 35.8)
2.Secondary Outcome
Title Duration of Objective Response (OR) Assessed by the Independent Review Facility Using Response Evaluation Criteria in Solid Tumors (RECIST)
Hide Description For patients who achieved an objective response, duration of objective response was defined as the time from the first tumor assessment that supported a patient's objective response to the time of disease progression or death on study (ie, death from any cause within 30 days of the last dose of study drug), whichever occurred first. Disease progression was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of 1 or more new lesions or the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions. For participants who experienced no disease progression and did not die while on study, data were censored at the date of the last tumor assessment. Kaplan-Meier methodology was used to estimate the duration of objective response.
Time Frame Randomization until the final analysis cut-off date of 25 Jun 2009 (end of the study, approximately 12 months after the last patient was enrolled, up to 23 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Patients who had an objective response in the efficacy evaluable population: All patients who received at least 1 dose of study drug and who underwent a baseline and at least 1 post-baseline tumor assessment or died while in the study from any cause within 30 days of the last dose of study drug.
Arm/Group Title Trastuzumab Emtansine 3.6 mg/kg
Hide Arm/Group Description:
Patients received trastuzumab emtansine 3.6 mg/kg intravenously on Day 1 of each 21 day cycle for a maximum of 1 year. The total dose was dependent on the patient's weight on Day 1 of each cycle.
Overall Number of Participants Analyzed 108
Median (95% Confidence Interval)
Unit of Measure: Months
NA [1] 
(6.2 to NA)
[1]
The median and the upper limit of the 95% confidence interval were not reached because of insufficient events.
3.Secondary Outcome
Title Progression-free Survival (PFS) Assessed by the Independent Review Facility Using Response Evaluation Criteria in Solid Tumors (RECIST)
Hide Description Progression-free survival (PFS) was defined as the time from the first day of study treatment to documented disease progression or death on study (ie, death from any cause within 30 days of the last dose of study drug), whichever occurred first. Disease progression was at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of 1 or more new lesions or the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions. For patients who experienced no disease progression and did not die while on study, data were censored at the date of the last tumor assessment. Kaplan-Meier methodology was used to estimate PFS.
Time Frame Randomization until the final analysis cut-off date of 25 Jun 2009 (end of the study, approximately 12 months after the last patient was enrolled, up to 23 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Efficacy evaluable population: All patients who received at least 1 dose of study drug and who underwent a baseline and at least 1 post-baseline tumor assessment or died while in the study from any cause within 30 days of the last dose of study drug.
Arm/Group Title Trastuzumab Emtansine 3.6 mg/kg
Hide Arm/Group Description:
Patients received trastuzumab emtansine 3.6 mg/kg intravenously on Day 1 of each 21 day cycle for a maximum of 1 year. The total dose was dependent on the patient's weight on Day 1 of each cycle.
Overall Number of Participants Analyzed 108
Median (95% Confidence Interval)
Unit of Measure: Months
4.6
(3.9 to 8.6)
4.Secondary Outcome
Title Objective Response Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST)
Hide Description Objective response was defined as a complete response (CR) or partial response (PR) determined on 2 consecutive occasions ≥ 4 weeks apart, using Response Evaluation Criteria in Solid Tumors (RECIST). CR: The disappearance of all target lesions and all non-target lesions, normalization of tumor marker level, and no new lesions. PR: Disappearance of all target lesions and persistence of ≥ 1 non-target lesions 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, and no new lesions or unequivocal progression of existing non-target lesions.
Time Frame Randomization until the final analysis cut-off date of 25 Jun 2009 (end of the study, approximately 12 months after the last patient was enrolled, up to 23 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Efficacy evaluable population: All patients who received at least 1 dose of study drug and who underwent a baseline and at least 1 post-baseline tumor assessment or died while in the study from any cause within 30 days of the last dose of study drug.
Arm/Group Title Trastuzumab Emtansine 3.6 mg/kg
Hide Arm/Group Description:
Patients received trastuzumab emtansine 3.6 mg/kg intravenously on Day 1 of each 21 day cycle for a maximum of 1 year. The total dose was dependent on the patient's weight on Day 1 of each cycle.
Overall Number of Participants Analyzed 108
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of patients
38.9
(29.7 to 48.5)
5.Secondary Outcome
Title Duration of Objective Response Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST)
Hide Description For patients who achieved an objective response, duration of objective response was defined as the time from the first tumor assessment that supported a patient's objective response to the time of disease progression or death on study (ie, death from any cause within 30 days of the last dose of study drug), whichever occurred first. Disease progression was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of 1 or more new lesions or the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions. For participants who experienced no disease progression and did not die while on study, data were censored at the date of the last tumor assessment. Kaplan-Meier methodology was used to estimate the duration of objective response.
Time Frame Randomization until the final analysis cut-off date of 25 Jun 2009 (end of the study, approximately 12 months after the last patient was enrolled, up to 23 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Patients who had an objective response in the efficacy evaluable population: All patients who received at least 1 dose of study drug and who underwent a baseline and at least 1 post-baseline tumor assessment or died while in the study from any cause within 30 days of the last dose of study drug.
Arm/Group Title Trastuzumab Emtansine 3.6 mg/kg
Hide Arm/Group Description:
Patients received trastuzumab emtansine 3.6 mg/kg intravenously on Day 1 of each 21 day cycle for a maximum of 1 year. The total dose was dependent on the patient's weight on Day 1 of each cycle.
Overall Number of Participants Analyzed 108
Median (95% Confidence Interval)
Unit of Measure: Months
9.4 [1] 
(7.0 to NA)
[1]
The upper limit of the 95% confidence interval were not reached because of insufficient events.
6.Secondary Outcome
Title Progression-free Survival Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST)
Hide Description Progression-free survival (PFS) was defined as the time from the first day of study treatment to documented disease progression or death on study (ie, death from any cause within 30 days of the last dose of study drug), whichever occurred first. Disease progression was at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of 1 or more new lesions or the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions. For patients who experienced no disease progression and did not die while on study, data were censored at the date of the last tumor assessment. Kaplan-Meier methodology was used to estimate PFS.
Time Frame Randomization until the final analysis cut-off date of 25 Jun 2009 (end of the study, approximately 12 months after the last patient was enrolled, up to 23 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Efficacy evaluable population: All patients who received at least 1 dose of study drug and who underwent a baseline and at least 1 post-baseline tumor assessment or died while in the study from any cause within 30 days of the last dose of study drug.
Arm/Group Title Trastuzumab Emtansine 3.6 mg/kg
Hide Arm/Group Description:
Patients received trastuzumab emtansine 3.6 mg/kg intravenously on Day 1 of each 21 day cycle for a maximum of 1 year. The total dose was dependent on the patient's weight on Day 1 of each cycle.
Overall Number of Participants Analyzed 108
Median (95% Confidence Interval)
Unit of Measure: Months
4.6
(4.1 to 6.0)
Time Frame Adverse events were recorded from randomization through the end of the study.
Adverse Event Reporting Description Safety population: All patients who received any amount of trastuzumab emtansine.
 
Arm/Group Title Trastuzumab Emtansine 3.6 mg/kg
Hide Arm/Group Description Patients received trastuzumab emtansine 3.6 mg/kg intravenously on Day 1 of each 21 day cycle for a maximum of 1 year. The total dose was dependent on the patient's weight on Day 1 of each cycle.
All-Cause Mortality
Trastuzumab Emtansine 3.6 mg/kg
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Trastuzumab Emtansine 3.6 mg/kg
Affected / at Risk (%)
Total   30/112 (26.79%) 
Blood and lymphatic system disorders   
Thrombocytopenia  1  1/112 (0.89%) 
Gastrointestinal disorders   
Dysphagia  1  1/112 (0.89%) 
Haemorrhoidal haemorrhage  1  1/112 (0.89%) 
Oesophageal stenosis  1  1/112 (0.89%) 
Upper gastrointestinal haemorrhage  1  1/112 (0.89%) 
General disorders   
Asthenia  1  1/112 (0.89%) 
Disease progression  1  1/112 (0.89%) 
Hepatobiliary disorders   
Hepatotoxicity  1  1/112 (0.89%) 
Infections and infestations   
Cellulitis  1  3/112 (2.68%) 
Pneumonia  1  2/112 (1.79%) 
Osteomyelitis  1  1/112 (0.89%) 
Urosepsis  1  1/112 (0.89%) 
Injury, poisoning and procedural complications   
Hip fracture  1  1/112 (0.89%) 
Subdural haemorrhage  1  1/112 (0.89%) 
Investigations   
Hepatic enzyme increased  1  1/112 (0.89%) 
Platelet count decreased  1  1/112 (0.89%) 
White blood cell count increased  1  1/112 (0.89%) 
Metabolism and nutrition disorders   
Dehydration  1  1/112 (0.89%) 
Failure to thrive  1  1/112 (0.89%) 
Musculoskeletal and connective tissue disorders   
Back pain  1  2/112 (1.79%) 
Arthralgia  1  1/112 (0.89%) 
Groin pain  1  1/112 (0.89%) 
Musculoskeletal chest pain  1  1/112 (0.89%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Acute myeloid leukaemia  1  1/112 (0.89%) 
Nervous system disorders   
Convulsion  1  2/112 (1.79%) 
Altered state of consciousness  1  1/112 (0.89%) 
Aphasia  1  1/112 (0.89%) 
Cerebrovascular accident  1  1/112 (0.89%) 
Psychiatric disorders   
Confusional state  1  2/112 (1.79%) 
Respiratory, thoracic and mediastinal disorders   
Dyspnoea  1  2/112 (1.79%) 
Pleural effusion  1  2/112 (1.79%) 
Pneumothorax  1  1/112 (0.89%) 
Respiratory failure  1  1/112 (0.89%) 
Vascular disorders   
Deep vein thrombosis  1  1/112 (0.89%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (11.1)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Trastuzumab Emtansine 3.6 mg/kg
Affected / at Risk (%)
Total   110/112 (98.21%) 
Blood and lymphatic system disorders   
Anaemia  1  23/112 (20.54%) 
Thrombocytopenia  1  18/112 (16.07%) 
Neutropenia  1  7/112 (6.25%) 
Eye disorders   
Dry eye  1  11/112 (9.82%) 
Lacrimation increased  1  9/112 (8.04%) 
Vision blurred  1  6/112 (5.36%) 
Visual impairment  1  6/112 (5.36%) 
Gastrointestinal disorders   
Nausea  1  57/112 (50.89%) 
Constipation  1  34/112 (30.36%) 
Diarrhoea  1  29/112 (25.89%) 
Vomiting  1  27/112 (24.11%) 
Dry mouth  1  16/112 (14.29%) 
Abdominal pain  1  12/112 (10.71%) 
Dyspepsia  1  12/112 (10.71%) 
Abdominal pain upper  1  9/112 (8.04%) 
Gastrooesophageal reflux disease  1  8/112 (7.14%) 
Abdominal discomfort  1  6/112 (5.36%) 
General disorders   
Fatigue  1  73/112 (65.18%) 
Pyrexia  1  39/112 (34.82%) 
Chills  1  22/112 (19.64%) 
Pain  1  13/112 (11.61%) 
Oedema peripheral  1  12/112 (10.71%) 
Chest pain  1  10/112 (8.93%) 
Asthenia  1  7/112 (6.25%) 
Influenza like illness  1  7/112 (6.25%) 
Infusion related reaction  1  7/112 (6.25%) 
Infections and infestations   
Upper respiratory tract infection  1  20/112 (17.86%) 
Urinary tract infection  1  18/112 (16.07%) 
Injury, poisoning and procedural complications   
Contusion  1  12/112 (10.71%) 
Investigations   
Weight decreased  1  13/112 (11.61%) 
Metabolism and nutrition disorders   
Hypokalaemia  1  27/112 (24.11%) 
Anorexia  1  22/112 (19.64%) 
Decreased appetite  1  16/112 (14.29%) 
Dehydration  1  6/112 (5.36%) 
Musculoskeletal and connective tissue disorders   
Pain in extremity  1  25/112 (22.32%) 
Arthralgia  1  24/112 (21.43%) 
Back pain  1  14/112 (12.50%) 
Musculoskeletal pain  1  13/112 (11.61%) 
Myalgia  1  11/112 (9.82%) 
Muscle spasms  1  10/112 (8.93%) 
Musculoskeletal chest pain  1  9/112 (8.04%) 
Neck pain  1  8/112 (7.14%) 
Muscular weakness  1  6/112 (5.36%) 
Nervous system disorders   
Headache  1  45/112 (40.18%) 
Neuropathy peripheral  1  20/112 (17.86%) 
Dizziness  1  13/112 (11.61%) 
Dysgeusia  1  7/112 (6.25%) 
Psychiatric disorders   
Insomnia  1  15/112 (13.39%) 
Depression  1  14/112 (12.50%) 
Anxiety  1  12/112 (10.71%) 
Confusional state  1  7/112 (6.25%) 
Respiratory, thoracic and mediastinal disorders   
Epistaxis  1  40/112 (35.71%) 
Cough  1  31/112 (27.68%) 
Dyspnoea  1  23/112 (20.54%) 
Rhinorrhoea  1  9/112 (8.04%) 
Oropharyngeal pain  1  8/112 (7.14%) 
Skin and subcutaneous tissue disorders   
Rash  1  19/112 (16.96%) 
Pruritus  1  8/112 (7.14%) 
Vascular disorders   
Hypertension  1  7/112 (6.25%) 
Hot flush  1  6/112 (5.36%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (11.1)
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: Genentech, Inc.
Phone: 800 821-8590
Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT00509769     History of Changes
Other Study ID Numbers: TDM4258g
First Submitted: July 27, 2007
First Posted: July 31, 2007
Results First Submitted: February 22, 2013
Results First Posted: April 2, 2013
Last Update Posted: April 2, 2013