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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01419197
First received: August 16, 2011
Last updated: April 3, 2014
Last verified: April 2014
Results First Received: February 7, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   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
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

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.

Participant Flow:   Overall Study
    Trastuzumab Emtansine     Treatment of Physician’s Choice  
STARTED     404     198  
Crossed-over to Trastuzumab Emtansine     0     44  
COMPLETED     319     125  
NOT COMPLETED     85     73  
Death                 61                 44  
Lost to Follow-up                 2                 0  
Non-compliance                 1                 1  
Withdrawal by Subject                 19                 26  
Physician Decision                 2                 2  



  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  
Number of Participants  
[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) ]


  Serious Adverse Events


  Other Adverse Events
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Time Frame After initiation of study treatment, adverse events (AE) were collected until 30 days following the last administration of study treatment or study discontinuation. After this period, only serious AEs considered related to study treatment were reported.
Additional Description Safety population: All randomized participants who received any amount of study treatment. 15 participants did not receive any treatment, trastuzumab emtansine = 2 and treatment of physician’s choice = 13. One treatment of physician’s choice participant received trastuzumab emtansine in error and was included in that arm for all safety analyses.

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

Reporting Groups
  Description
Trastuzumab Emtansine - Planned Treatment Period 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 - Planned Treatment Period 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-crossover Period 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 - Planned Treatment Period     Treatment of Physician’s Choice - Planned Treatment Period     Trastuzumab Emtansine - Post-crossover Period  
Total, other (not including serious) adverse events        
# participants affected / at risk     351/403     143/184     24/44  
Blood and lymphatic system disorders        
Thrombocytopenia † 1      
# participants affected / at risk     60/403 (14.89%)     5/184 (2.72%)     3/44 (6.82%)  
Neutropenia † 1      
# participants affected / at risk     21/403 (5.21%)     39/184 (21.20%)     0/44 (0.00%)  
Anaemia † 1      
# participants affected / at risk     35/403 (8.68%)     18/184 (9.78%)     0/44 (0.00%)  
Leukopenia † 1      
# participants affected / at risk     3/403 (0.74%)     11/184 (5.98%)     0/44 (0.00%)  
Gastrointestinal disorders        
Nausea † 1      
# participants affected / at risk     133/403 (33.00%)     39/184 (21.20%)     5/44 (11.36%)  
Dry mouth † 1      
# participants affected / at risk     49/403 (12.16%)     0/184 (0.00%)     4/44 (9.09%)  
Diarrhoea † 1      
# participants affected / at risk     39/403 (9.68%)     39/184 (21.20%)     3/44 (6.82%)  
Constipation † 1      
# participants affected / at risk     78/403 (19.35%)     29/184 (15.76%)     0/44 (0.00%)  
Vomiting † 1      
# participants affected / at risk     70/403 (17.37%)     14/184 (7.61%)     0/44 (0.00%)  
Abdominal pain † 1      
# participants affected / at risk     23/403 (5.71%)     20/184 (10.87%)     0/44 (0.00%)  
Dyspepsia † 1      
# participants affected / at risk     14/403 (3.47%)     11/184 (5.98%)     0/44 (0.00%)  
General disorders        
Pyrexia † 1      
# participants affected / at risk     64/403 (15.88%)     20/184 (10.87%)     4/44 (9.09%)  
Fatigue † 1      
# participants affected / at risk     108/403 (26.80%)     46/184 (25.00%)     3/44 (6.82%)  
Asthenia † 1      
# participants affected / at risk     61/403 (15.14%)     29/184 (15.76%)     0/44 (0.00%)  
Oedema peripheral † 1      
# participants affected / at risk     23/403 (5.71%)     10/184 (5.43%)     0/44 (0.00%)  
Mucosal inflammation † 1      
# participants affected / at risk     13/403 (3.23%)     12/184 (6.52%)     0/44 (0.00%)  
Infections and infestations        
Upper respiratory tract infection † 1      
# participants affected / at risk     23/403 (5.71%)     7/184 (3.80%)     3/44 (6.82%)  
Nasopharyngitis † 1      
# participants affected / at risk     25/403 (6.20%)     9/184 (4.89%)     0/44 (0.00%)  
Investigations        
Aspartate aminotransferase increased † 1      
# participants affected / at risk     34/403 (8.44%)     10/184 (5.43%)     0/44 (0.00%)  
Alanine aminotransferase increased † 1      
# participants affected / at risk     26/403 (6.45%)     7/184 (3.80%)     0/44 (0.00%)  
Metabolism and nutrition disorders        
Decreased appetite † 1      
# participants affected / at risk     57/403 (14.14%)     23/184 (12.50%)     6/44 (13.64%)  
Hypokalaemia † 1      
# participants affected / at risk     21/403 (5.21%)     4/184 (2.17%)     0/44 (0.00%)  
Musculoskeletal and connective tissue disorders        
Myalgia † 1      
# participants affected / at risk     42/403 (10.42%)     14/184 (7.61%)     0/44 (0.00%)  
Arthralgia † 1      
# participants affected / at risk     45/403 (11.17%)     7/184 (3.80%)     0/44 (0.00%)  
Pain in extremity † 1      
# participants affected / at risk     35/403 (8.68%)     7/184 (3.80%)     0/44 (0.00%)  
Back pain † 1      
# participants affected / at risk     25/403 (6.20%)     11/184 (5.98%)     0/44 (0.00%)  
Nervous system disorders        
Headache † 1      
# participants affected / at risk     89/403 (22.08%)     15/184 (8.15%)     3/44 (6.82%)  
Dizziness † 1      
# participants affected / at risk     24/403 (5.96%)     5/184 (2.72%)     0/44 (0.00%)  
Psychiatric disorders        
Insomnia † 1      
# participants affected / at risk     25/403 (6.20%)     6/184 (3.26%)     3/44 (6.82%)  
Respiratory, thoracic and mediastinal disorders        
Cough † 1      
# participants affected / at risk     63/403 (15.63%)     19/184 (10.33%)     4/44 (9.09%)  
Epistaxis † 1      
# participants affected / at risk     47/403 (11.66%)     5/184 (2.72%)     0/44 (0.00%)  
Dyspnoea † 1      
# participants affected / at risk     35/403 (8.68%)     15/184 (8.15%)     0/44 (0.00%)  
Skin and subcutaneous tissue disorders        
Rash † 1      
# participants affected / at risk     19/403 (4.71%)     19/184 (10.33%)     0/44 (0.00%)  
Pruritus † 1      
# participants affected / at risk     17/403 (4.22%)     14/184 (7.61%)     0/44 (0.00%)  
Alopecia † 1      
# participants affected / at risk     4/403 (0.99%)     18/184 (9.78%)     0/44 (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


No publications provided


Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01419197     History of Changes
Other Study ID Numbers: TDM4997g, BO25734, 2011-000509-29
Study First Received: August 16, 2011
Results First Received: February 7, 2014
Last Updated: April 3, 2014
Health Authority: United States: Food and Drug Administration