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A Study of Trastuzumab Emtansine in Comparison With Treatment of Physician's Choice in Participants With HER2-positive Breast Cancer Who Have Received at Least Two Prior Regimens of HER2-directed Therapy (TH3RESA)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01419197
First received: August 16, 2011
Last updated: August 17, 2016
Last verified: August 2016
Results First Received: February 7, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Breast Cancer
Interventions: Drug: Trastuzumab emtansine
Drug: Treatment of physician's choice

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A total of 602 patients were randomized to the study (404 to receive Trastuzumab Emtansine and 198 to receive Treatment of Physician’s Choice).

Reporting Groups
  Description
Trastuzumab Emtansine Trastuzumab emtansine 3.6 mg/kg intravenously every 3 weeks until disease progression (as assessed by the investigator) or unmanageable toxicity.
Treatment of Physician’s Choice Treatment of physician’s choice until disease progression (as assessed by the investigator) or unmanageable toxicity. The treatments included single-agent chemotherapy, single-agent or dual-agent hormonal therapy for hormone receptor positive-disease, and human epidermal growth factor receptor 2 (HER2)-directed therapy.

Participant Flow:   Overall Study
    Trastuzumab Emtansine   Treatment of Physician’s Choice
STARTED   404   198 
Switched to Trastuzumab Emtansine   0   94 
COMPLETED   0   0 
NOT COMPLETED   404   198 
Death                247                122 
Physician Decision                4                4 
Non-compliance                3                1 
Withdrawal by Subject                33                32 
Study Completed by Sponsor                103                34 
Reason Not Specified                0                1 
Lost to Follow-up                14                4 



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Randomized population: All participants who were randomized to the study.

Reporting Groups
  Description
Trastuzumab Emtansine Trastuzumab emtansine 3.6 mg/kg intravenously every 3 weeks until disease progression (as assessed by the investigator) or unmanageable toxicity.
Treatment of Physician’s Choice Treatment of physician’s choice until disease progression (as assessed by the investigator) or unmanageable toxicity. The treatments included single-agent chemotherapy, single-agent or dual-agent hormonal therapy for hormone receptor positive-disease, and HER2-directed therapy.
Total Total of all reporting groups

Baseline Measures
   Trastuzumab Emtansine   Treatment of Physician’s Choice   Total 
Overall Participants Analyzed 
[Units: Participants]
 404   198   602 
Age 
[Units: Years]
Mean (Standard Deviation)
 53.3  (10.4)   54.3  (10.8)   53.6  (10.5) 
Gender 
[Units: Participants]
     
Female   401   197   598 
Male   3   1   4 


  Outcome Measures
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1.  Primary:   Progression-free Survival   [ Time Frame: Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years) ]

2.  Primary:   Overall Survival   [ Time Frame: Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years) ]

3.  Secondary:   Percentage of Participants With an Objective Response   [ Time Frame: Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years) ]

4.  Secondary:   Duration of the Objective Response   [ Time Frame: Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years) ]

5.  Secondary:   6-month and 1-year Survival   [ Time Frame: Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years) ]

6.  Secondary:   Time to Pain Symptom Progression   [ Time Frame: Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years) ]

7.  Secondary:   Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle   [ Time Frame: Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years) ]

8.  Secondary:   Overall Survival (Final Analysis)   [ Time Frame: Baseline to the clinical cut-off date of 13 Feb 2015 (up to 4 years) ]

9.  Secondary:   6-month and 1-year Survival (Final Analysis)   [ Time Frame: Baseline to the clinical cut-off date of 13 Feb 2015 (up to 4 years) ]


  Serious Adverse Events


  Other Adverse Events
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Time Frame Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years).
Additional Description Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).

Frequency Threshold
Threshold above which other adverse events are reported   5%  

Reporting Groups
  Description
Trastuzumab Emtansine Trastuzumab emtansine 3.6 mg/kg intravenously every 3 weeks until disease progression (as assessed by the investigator) or unmanageable toxicity.
Treatment of Physician’s Choice (TPC) Treatment of physician’s choice until disease progression (as assessed by the investigator) or unmanageable toxicity. The treatments included single-agent chemotherapy, single-agent or dual-agent hormonal therapy for hormone receptor positive-disease, and HER2-directed therapy.
Trastuzumab Emtansine - Post TPC Treatment Switch Participants, who switched treatment in the Treatment of Physician's Choice arm to trastuzumab emtansine, were administered trastuzumab emtansine 3.6 mg/kg intravenously every 3 weeks until disease progression (as assessed by the investigator) or unmanageable toxicity.

Other Adverse Events
    Trastuzumab Emtansine   Treatment of Physician’s Choice (TPC)   Trastuzumab Emtansine - Post TPC Treatment Switch
Total, Other (not including serious) Adverse Events       
# participants affected / at risk   371/403 (92.06%)   148/184 (80.43%)   74/94 (78.72%) 
Blood and lymphatic system disorders       
Anaemia † 1       
# participants affected / at risk   45/403 (11.17%)   19/184 (10.33%)   7/94 (7.45%) 
Leukopenia † 1       
# participants affected / at risk   9/403 (2.23%)   11/184 (5.98%)   0/94 (0.00%) 
Neutropenia † 1       
# participants affected / at risk   30/403 (7.44%)   39/184 (21.20%)   5/94 (5.32%) 
Thrombocytopenia † 1       
# participants affected / at risk   81/403 (20.10%)   6/184 (3.26%)   17/94 (18.09%) 
Eye disorders       
Lacrimation increased † 1       
# participants affected / at risk   0/403 (0.00%)   0/184 (0.00%)   5/94 (5.32%) 
Gastrointestinal disorders       
Abdominal pain † 1       
# participants affected / at risk   27/403 (6.70%)   20/184 (10.87%)   9/94 (9.57%) 
Constipation † 1       
# participants affected / at risk   90/403 (22.33%)   32/184 (17.39%)   7/94 (7.45%) 
Diarrhoea † 1       
# participants affected / at risk   52/403 (12.90%)   40/184 (21.74%)   10/94 (10.64%) 
Dry mouth † 1       
# participants affected / at risk   51/403 (12.66%)   2/184 (1.09%)   9/94 (9.57%) 
Dyspepsia † 1       
# participants affected / at risk   21/403 (5.21%)   12/184 (6.52%)   0/94 (0.00%) 
Gingival bleeding † 1       
# participants affected / at risk   21/403 (5.21%)   0/184 (0.00%)   0/94 (0.00%) 
Nausea † 1       
# participants affected / at risk   144/403 (35.73%)   40/184 (21.74%)   16/94 (17.02%) 
Stomatitis † 1       
# participants affected / at risk   13/403 (3.23%)   11/184 (5.98%)   0/94 (0.00%) 
Vomiting † 1       
# participants affected / at risk   77/403 (19.11%)   16/184 (8.70%)   10/94 (10.64%) 
Abdominal pain upper † 1       
# participants affected / at risk   0/403 (0.00%)   0/184 (0.00%)   7/94 (7.45%) 
General disorders       
Asthenia † 1       
# participants affected / at risk   76/403 (18.86%)   33/184 (17.93%)   15/94 (15.96%) 
Chills † 1       
# participants affected / at risk   21/403 (5.21%)   4/184 (2.17%)   0/94 (0.00%) 
Fatigue † 1       
# participants affected / at risk   123/403 (30.52%)   48/184 (26.09%)   10/94 (10.64%) 
Influenza like illness † 1       
# participants affected / at risk   21/403 (5.21%)   2/184 (1.09%)   0/94 (0.00%) 
Mucosal inflammation † 1       
# participants affected / at risk   17/403 (4.22%)   10/184 (5.43%)   7/94 (7.45%) 
Oedema peripheral † 1       
# participants affected / at risk   26/403 (6.45%)   11/184 (5.98%)   0/94 (0.00%) 
Pyrexia † 1       
# participants affected / at risk   77/403 (19.11%)   22/184 (11.96%)   14/94 (14.89%) 
Pain † 1       
# participants affected / at risk   0/403 (0.00%)   0/184 (0.00%)   5/94 (5.32%) 
Infections and infestations       
Nasopharyngitis † 1       
# participants affected / at risk   35/403 (8.68%)   12/184 (6.52%)   6/94 (6.38%) 
Upper respiratory tract infection † 1       
# participants affected / at risk   35/403 (8.68%)   8/184 (4.35%)   8/94 (8.51%) 
Urinary tract infection † 1       
# participants affected / at risk   26/403 (6.45%)   7/184 (3.80%)   9/94 (9.57%) 
Sinusitis † 1       
# participants affected / at risk   0/403 (0.00%)   0/184 (0.00%)   5/94 (5.32%) 
Investigations       
Alanine aminotransferase increased † 1       
# participants affected / at risk   38/403 (9.43%)   10/184 (5.43%)   7/94 (7.45%) 
Aspartate aminotransferase increased † 1       
# participants affected / at risk   51/403 (12.66%)   13/184 (7.07%)   13/94 (13.83%) 
Blood alkaline phosphatase increased † 1       
# participants affected / at risk   21/403 (5.21%)   5/184 (2.72%)   7/94 (7.45%) 
Blood bilirubin increased † 1       
# participants affected / at risk   38/403 (9.43%)   2/184 (1.09%)   5/94 (5.32%) 
Ejection fraction decreased † 1       
# participants affected / at risk   11/403 (2.73%)   12/184 (6.52%)   0/94 (0.00%) 
Metabolism and nutrition disorders       
Decreased appetite † 1       
# participants affected / at risk   66/403 (16.38%)   25/184 (13.59%)   15/94 (15.96%) 
Hypokalaemia † 1       
# participants affected / at risk   30/403 (7.44%)   4/184 (2.17%)   6/94 (6.38%) 
Hyperglycaemia † 1       
# participants affected / at risk   0/403 (0.00%)   0/184 (0.00%)   5/94 (5.32%) 
Musculoskeletal and connective tissue disorders       
Arthralgia † 1       
# participants affected / at risk   60/403 (14.89%)   8/184 (4.35%)   7/94 (7.45%) 
Back pain † 1       
# participants affected / at risk   35/403 (8.68%)   13/184 (7.07%)   6/94 (6.38%) 
Bone pain † 1       
# participants affected / at risk   22/403 (5.46%)   7/184 (3.80%)   0/94 (0.00%) 
Muscle spasms † 1       
# participants affected / at risk   26/403 (6.45%)   9/184 (4.89%)   0/94 (0.00%) 
Musculoskeletal pain † 1       
# participants affected / at risk   18/403 (4.47%)   10/184 (5.43%)   7/94 (7.45%) 
Myalgia † 1       
# participants affected / at risk   47/403 (11.66%)   14/184 (7.61%)   6/94 (6.38%) 
Pain in extremity † 1       
# participants affected / at risk   44/403 (10.92%)   9/184 (4.89%)   0/94 (0.00%) 
Nervous system disorders       
Dizziness † 1       
# participants affected / at risk   31/403 (7.69%)   6/184 (3.26%)   6/94 (6.38%) 
Headache † 1       
# participants affected / at risk   100/403 (24.81%)   22/184 (11.96%)   16/94 (17.02%) 
Neuropathy peripheral † 1       
# participants affected / at risk   20/403 (4.96%)   10/184 (5.43%)   7/94 (7.45%) 
Paraesthesia † 1       
# participants affected / at risk   28/403 (6.95%)   11/184 (5.98%)   9/94 (9.57%) 
Psychiatric disorders       
Insomnia † 1       
# participants affected / at risk   35/403 (8.68%)   6/184 (3.26%)   8/94 (8.51%) 
Respiratory, thoracic and mediastinal disorders       
Cough † 1       
# participants affected / at risk   76/403 (18.86%)   24/184 (13.04%)   12/94 (12.77%) 
Dyspnoea † 1       
# participants affected / at risk   42/403 (10.42%)   21/184 (11.41%)   6/94 (6.38%) 
Epistaxis † 1       
# participants affected / at risk   67/403 (16.63%)   7/184 (3.80%)   12/94 (12.77%) 
Skin and subcutaneous tissue disorders       
Alopecia † 1       
# participants affected / at risk   9/403 (2.23%)   20/184 (10.87%)   0/94 (0.00%) 
Pruritus † 1       
# participants affected / at risk   23/403 (5.71%)   17/184 (9.24%)   0/94 (0.00%) 
Rash † 1       
# participants affected / at risk   27/403 (6.70%)   19/184 (10.33%)   0/94 (0.00%) 
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA (16.0)



  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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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 agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Medical Communications
Organization: Hoffmann-La Roche
phone: 800 821-8590


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01419197     History of Changes
Other Study ID Numbers: TDM4997g
BO25734 ( Other Identifier: Hoffmann-La Roche )
2011-000509-29 ( EudraCT Number )
Study First Received: August 16, 2011
Results First Received: February 7, 2014
Last Updated: August 17, 2016