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
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Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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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
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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.

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.

Serious Adverse Events
    Trastuzumab Emtansine - Planned Treatment Period     Treatment of Physician’s Choice - Planned Treatment Period     Trastuzumab Emtansine - Post-crossover Period  
Total, serious adverse events        
# participants affected / at risk     74/403 (18.36%)     38/184 (20.65%)     2/44 (4.55%)  
Blood and lymphatic system disorders        
Febrile neutropenia † 1      
# participants affected / at risk     1/403 (0.25%)     7/184 (3.80%)     0/44 (0.00%)  
Neutropenia † 1      
# participants affected / at risk     1/403 (0.25%)     2/184 (1.09%)     0/44 (0.00%)  
Anaemia † 1      
# participants affected / at risk     1/403 (0.25%)     1/184 (0.54%)     0/44 (0.00%)  
Thrombocytopenia † 1      
# participants affected / at risk     1/403 (0.25%)     1/184 (0.54%)     0/44 (0.00%)  
Granulocytopenia † 1      
# participants affected / at risk     0/403 (0.00%)     1/184 (0.54%)     0/44 (0.00%)  
Ear and labyrinth disorders        
Vertigo † 1      
# participants affected / at risk     1/403 (0.25%)     0/184 (0.00%)     0/44 (0.00%)  
Endocrine disorders        
Hypercalcaemia of malignancy † 1      
# participants affected / at risk     0/403 (0.00%)     1/184 (0.54%)     0/44 (0.00%)  
Eye disorders        
Vision blurred † 1      
# participants affected / at risk     1/403 (0.25%)     0/184 (0.00%)     0/44 (0.00%)  
Gastrointestinal disorders        
Abdominal pain † 1      
# participants affected / at risk     3/403 (0.74%)     3/184 (1.63%)     0/44 (0.00%)  
Diarrhoea † 1      
# participants affected / at risk     2/403 (0.50%)     1/184 (0.54%)     0/44 (0.00%)  
Vomiting † 1      
# participants affected / at risk     1/403 (0.25%)     2/184 (1.09%)     0/44 (0.00%)  
Colitis † 1      
# participants affected / at risk     2/403 (0.50%)     0/184 (0.00%)     0/44 (0.00%)  
Nausea † 1      
# participants affected / at risk     0/403 (0.00%)     2/184 (1.09%)     0/44 (0.00%)  
Abdominal pain upper † 1      
# participants affected / at risk     0/403 (0.00%)     1/184 (0.54%)     0/44 (0.00%)  
Abdominal wall haematoma † 1      
# participants affected / at risk     1/403 (0.25%)     0/184 (0.00%)     0/44 (0.00%)  
Gastric haemorrhage † 1      
# participants affected / at risk     1/403 (0.25%)     0/184 (0.00%)     0/44 (0.00%)  
Obstruction gastric † 1      
# participants affected / at risk     1/403 (0.25%)     0/184 (0.00%)     0/44 (0.00%)  
Pancreatitis † 1      
# participants affected / at risk     1/403 (0.25%)     0/184 (0.00%)     0/44 (0.00%)  
Proctitis haemorrhagic † 1      
# participants affected / at risk     1/403 (0.25%)     0/184 (0.00%)     0/44 (0.00%)  
Small intestinal obstruction † 1      
# participants affected / at risk     1/403 (0.25%)     0/184 (0.00%)     0/44 (0.00%)  
Upper gastrointestinal haemorrhage † 1      
# participants affected / at risk     0/403 (0.00%)     1/184 (0.54%)     0/44 (0.00%)  
General disorders        
Pyrexia † 1      
# participants affected / at risk     3/403 (0.74%)     2/184 (1.09%)     0/44 (0.00%)  
Oedema peripheral † 1      
# participants affected / at risk     1/403 (0.25%)     2/184 (1.09%)     0/44 (0.00%)  
Asthenia † 1      
# participants affected / at risk     2/403 (0.50%)     0/184 (0.00%)     0/44 (0.00%)  
Fatigue † 1      
# participants affected / at risk     1/403 (0.25%)     1/184 (0.54%)     0/44 (0.00%)  
Malaise † 1      
# participants affected / at risk     2/403 (0.50%)     0/184 (0.00%)     0/44 (0.00%)  
Adverse drug reaction † 1      
# participants affected / at risk     1/403 (0.25%)     0/184 (0.00%)     0/44 (0.00%)  
Device occlusion † 1      
# participants affected / at risk     1/403 (0.25%)     0/184 (0.00%)     0/44 (0.00%)  
General physical health deterioration † 1      
# participants affected / at risk     1/403 (0.25%)     0/184 (0.00%)     0/44 (0.00%)  
Non−cardiac chest pain † 1      
# participants affected / at risk     0/403 (0.00%)     1/184 (0.54%)     0/44 (0.00%)  
Pain † 1      
# participants affected / at risk     0/403 (0.00%)     1/184 (0.54%)     0/44 (0.00%)  
Spinal pain † 1      
# participants affected / at risk     1/403 (0.25%)     0/184 (0.00%)     0/44 (0.00%)  
Vessel puncture site haemorrhage † 1      
# participants affected / at risk     1/403 (0.25%)     0/184 (0.00%)     0/44 (0.00%)  
Hepatobiliary disorders        
Cholangitis † 1      
# participants affected / at risk     1/403 (0.25%)     0/184 (0.00%)     0/44 (0.00%)  
Cholecystitis † 1      
# participants affected / at risk     1/403 (0.25%)     0/184 (0.00%)     0/44 (0.00%)  
Immune system disorders        
Drug hypersensitivity † 1      
# participants affected / at risk     0/403 (0.00%)     1/184 (0.54%)     0/44 (0.00%)  
Hypersensitivity † 1      
# participants affected / at risk     1/403 (0.25%)     0/184 (0.00%)     0/44 (0.00%)  
Infections and infestations        
Cellulitis † 1      
# participants affected / at risk     2/403 (0.50%)     4/184 (2.17%)     1/44 (2.27%)  
Pneumonia † 1      
# participants affected / at risk     5/403 (1.24%)     0/184 (0.00%)     0/44 (0.00%)  
Urinary tract infection † 1      
# participants affected / at risk     3/403 (0.74%)     0/184 (0.00%)     0/44 (0.00%)  
Infection † 1      
# participants affected / at risk     2/403 (0.50%)     0/184 (0.00%)     0/44 (0.00%)  
Sepsis † 1      
# participants affected / at risk     2/403 (0.50%)     0/184 (0.00%)     0/44 (0.00%)  
Sinusitis † 1      
# participants affected / at risk     1/403 (0.25%)     1/184 (0.54%)     0/44 (0.00%)  
Breast infection † 1      
# participants affected / at risk     0/403 (0.00%)     1/184 (0.54%)     0/44 (0.00%)  
Clostridium bacteraemia † 1      
# participants affected / at risk     0/403 (0.00%)     1/184 (0.54%)     0/44 (0.00%)  
Device related infection † 1      
# participants affected / at risk     0/403 (0.00%)     1/184 (0.54%)     0/44 (0.00%)  
Enterocolitis infectious † 1      
# participants affected / at risk     0/403 (0.00%)     1/184 (0.54%)     0/44 (0.00%)  
Gastroenteritis † 1      
# participants affected / at risk     1/403 (0.25%)     0/184 (0.00%)     0/44 (0.00%)  
Infected fistula † 1      
# participants affected / at risk     1/403 (0.25%)     0/184 (0.00%)     0/44 (0.00%)  
Neutropenic sepsis † 1      
# participants affected / at risk     0/403 (0.00%)     1/184 (0.54%)     0/44 (0.00%)  
Pharyngotonsillitis † 1      
# participants affected / at risk     0/403 (0.00%)     1/184 (0.54%)     0/44 (0.00%)  
Tracheitis † 1      
# participants affected / at risk     1/403 (0.25%)     0/184 (0.00%)     0/44 (0.00%)  
Urosepsis † 1      
# participants affected / at risk     1/403 (0.25%)     0/184 (0.00%)     0/44 (0.00%)  
Wound infection † 1      
# participants affected / at risk     1/403 (0.25%)     0/184 (0.00%)     0/44 (0.00%)  
Injury, poisoning and procedural complications        
Infusion related reaction † 1      
# participants affected / at risk     1/403 (0.25%)     1/184 (0.54%)     0/44 (0.00%)  
Wound haemorrhage † 1      
# participants affected / at risk     1/403 (0.25%)     1/184 (0.54%)     0/44 (0.00%)  
Fall † 1      
# participants affected / at risk     1/403 (0.25%)     0/184 (0.00%)     0/44 (0.00%)  
Sternal fracture † 1      
# participants affected / at risk     1/403 (0.25%)     0/184 (0.00%)     0/44 (0.00%)  
Subdural haematoma † 1      
# participants affected / at risk     1/403 (0.25%)     0/184 (0.00%)     0/44 (0.00%)  
Subdural haemorrhage † 1      
# participants affected / at risk     1/403 (0.25%)     0/184 (0.00%)     0/44 (0.00%)  
Wound decomposition † 1      
# participants affected / at risk     0/403 (0.00%)     1/184 (0.54%)     0/44 (0.00%)  
Investigations        
White blood cell count decreased † 1      
# participants affected / at risk     0/403 (0.00%)     1/184 (0.54%)     0/44 (0.00%)  
Metabolism and nutrition disorders        
Hyponatraemia † 1      
# participants affected / at risk     3/403 (0.74%)     0/184 (0.00%)     0/44 (0.00%)  
Decreased appetite † 1      
# participants affected / at risk     1/403 (0.25%)     0/184 (0.00%)     0/44 (0.00%)  
Dehydration † 1      
# participants affected / at risk     1/403 (0.25%)     0/184 (0.00%)     0/44 (0.00%)  
Hypercalcaemia † 1      
# participants affected / at risk     1/403 (0.25%)     0/184 (0.00%)     0/44 (0.00%)  
Hyperglycaemia † 1      
# participants affected / at risk     1/403 (0.25%)     0/184 (0.00%)     0/44 (0.00%)  
Hypokalaemia † 1      
# participants affected / at risk     1/403 (0.25%)     0/184 (0.00%)     0/44 (0.00%)  
Hypophagia † 1      
# participants affected / at risk     1/403 (0.25%)     0/184 (0.00%)     0/44 (0.00%)  
Malnutrition † 1      
# participants affected / at risk     0/403 (0.00%)     1/184 (0.54%)     0/44 (0.00%)  
Musculoskeletal and connective tissue disorders        
Back pain † 1      
# participants affected / at risk     2/403 (0.50%)     0/184 (0.00%)     0/44 (0.00%)  
Arthralgia † 1      
# participants affected / at risk     1/403 (0.25%)     0/184 (0.00%)     0/44 (0.00%)  
Muscle haemorrhage † 1      
# participants affected / at risk     1/403 (0.25%)     0/184 (0.00%)     0/44 (0.00%)  
Musculoskeletal chest pain † 1      
# participants affected / at risk     0/403 (0.00%)     1/184 (0.54%)     0/44 (0.00%)  
Myalgia † 1      
# participants affected / at risk     0/403 (0.00%)     1/184 (0.54%)     0/44 (0.00%)  
Neoplasms benign, malignant and unspecified (incl cysts and polyps)        
Rectal adenocarcinoma † 1      
# participants affected / at risk     1/403 (0.25%)     0/184 (0.00%)     0/44 (0.00%)  
Tumour associated fever † 1      
# participants affected / at risk     1/403 (0.25%)     0/184 (0.00%)     0/44 (0.00%)  
Tumour haemorrhage † 1      
# participants affected / at risk     1/403 (0.25%)     0/184 (0.00%)     0/44 (0.00%)  
Tumour pain † 1      
# participants affected / at risk     0/403 (0.00%)     1/184 (0.54%)     0/44 (0.00%)  
Nervous system disorders        
Convulsion † 1      
# participants affected / at risk     5/403 (1.24%)     0/184 (0.00%)     0/44 (0.00%)  
Ataxia † 1      
# participants affected / at risk     0/403 (0.00%)     1/184 (0.54%)     0/44 (0.00%)  
Brain oedema † 1      
# participants affected / at risk     1/403 (0.25%)     0/184 (0.00%)     0/44 (0.00%)  
Burning sensation † 1      
# participants affected / at risk     0/403 (0.00%)     1/184 (0.54%)     0/44 (0.00%)  
Cerebral haemorrhage † 1      
# participants affected / at risk     1/403 (0.25%)     0/184 (0.00%)     0/44 (0.00%)  
Cognitive disorder † 1      
# participants affected / at risk     0/403 (0.00%)     1/184 (0.54%)     0/44 (0.00%)  
Depressed level of consciousness † 1      
# participants affected / at risk     1/403 (0.25%)     0/184 (0.00%)     0/44 (0.00%)  
Dizziness † 1      
# participants affected / at risk     1/403 (0.25%)     0/184 (0.00%)     0/44 (0.00%)  
Hepatic encephalopathy † 1      
# participants affected / at risk     1/403 (0.25%)     0/184 (0.00%)     0/44 (0.00%)  
Nervous system disorder † 1      
# participants affected / at risk     1/403 (0.25%)     0/184 (0.00%)     0/44 (0.00%)  
Paraesthesia † 1      
# participants affected / at risk     0/403 (0.00%)     1/184 (0.54%)     0/44 (0.00%)  
Paraparesis † 1      
# participants affected / at risk     0/403 (0.00%)     1/184 (0.54%)     0/44 (0.00%)  
Somnolence † 1      
# participants affected / at risk     1/403 (0.25%)     0/184 (0.00%)     0/44 (0.00%)  
Subarachnoid haemorrhage † 1      
# participants affected / at risk     1/403 (0.25%)     0/184 (0.00%)     0/44 (0.00%)  
Transient ischaemic attack † 1      
# participants affected / at risk     1/403 (0.25%)     0/184 (0.00%)     0/44 (0.00%)  
Psychiatric disorders        
Confusional state † 1      
# participants affected / at risk     1/403 (0.25%)     0/184 (0.00%)     0/44 (0.00%)  
Renal and urinary disorders        
Haematuria † 1      
# participants affected / at risk     1/403 (0.25%)     1/184 (0.54%)     0/44 (0.00%)  
Respiratory, thoracic and mediastinal disorders        
Dyspnoea † 1      
# participants affected / at risk     6/403 (1.49%)     3/184 (1.63%)     1/44 (2.27%)  
Pleural effusion † 1      
# participants affected / at risk     3/403 (0.74%)     2/184 (1.09%)     0/44 (0.00%)  
Pulmonary embolism † 1      
# participants affected / at risk     1/403 (0.25%)     2/184 (1.09%)     0/44 (0.00%)  
Pneumonitis † 1      
# participants affected / at risk     1/403 (0.25%)     1/184 (0.54%)     0/44 (0.00%)  
Epistaxis † 1      
# participants affected / at risk     1/403 (0.25%)     0/184 (0.00%)     0/44 (0.00%)  
Hydropneumothorax † 1      
# participants affected / at risk     0/403 (0.00%)     1/184 (0.54%)     0/44 (0.00%)  
Non−cardiogenic pulmonary oedema † 1      
# participants affected / at risk     0/403 (0.00%)     1/184 (0.54%)     0/44 (0.00%)  
Pleuritic pain † 1      
# participants affected / at risk     1/403 (0.25%)     0/184 (0.00%)     0/44 (0.00%)  
Pneumonia aspiration † 1      
# participants affected / at risk     1/403 (0.25%)     0/184 (0.00%)     0/44 (0.00%)  
Respiratory failure † 1      
# participants affected / at risk     1/403 (0.25%)     0/184 (0.00%)     0/44 (0.00%)  
Vascular disorders        
Lymphoedema † 1      
# participants affected / at risk     0/403 (0.00%)     1/184 (0.54%)     1/44 (2.27%)  
Deep vein thrombosis † 1      
# participants affected / at risk     2/403 (0.50%)     0/184 (0.00%)     0/44 (0.00%)  
Embolism † 1      
# participants affected / at risk     1/403 (0.25%)     0/184 (0.00%)     0/44 (0.00%)  
Embolism venous † 1      
# participants affected / at risk     0/403 (0.00%)     1/184 (0.54%)     0/44 (0.00%)  
Hypertensive crisis † 1      
# participants affected / at risk     1/403 (0.25%)     0/184 (0.00%)     0/44 (0.00%)  
Hypotension † 1      
# participants affected / at risk     1/403 (0.25%)     0/184 (0.00%)     0/44 (0.00%)  
Superior vena cava syndrome † 1      
# participants affected / at risk     1/403 (0.25%)     0/184 (0.00%)     0/44 (0.00%)  
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA (16.0)




  Other Adverse Events


  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