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

Study Overview
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Brief Summary
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This was a multi-institutional, open-label, single-arm, Phase II study of trastuzumab emtansine (T-DM1) administered by intravenous (IV) infusion to patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC).

Official Title
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A Phase II, Single-arm, Open-label Study of Trastuzumab-MCC-DM1 Administered Intravenously to Patients With HER2-Positive Metastatic Breast Cancer Who Have Progressed While Receiving HER2-Directed Therapy

Conditions
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Metastatic Breast Cancer

Intervention / Treatment
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* Drug: Trastuzumab emtansine [Kadcyla]


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent form. Human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC); tissue (slides or blocks) available for HER2 confirmation. History of progression on HER2-directed therapy for the treatment of HER2-positive breast cancer. At least 1, and no more than 3, chemotherapy regimens for MBC. Granulocyte count ≥ 1500/μL, platelet count ≥ 100,000/μL, and hemoglobin ≥ 9 g/dL. Serum bilirubin ≤ 1.5 mg/dL, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase ≤ 2.5x the upper limit of normal (ULN). Serum creatinine ≤ 1.5 mg/dL or creatinine clearance ≥ 60 mL/min. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2. Exclusion Criteria: Any chemotherapy, hormonal therapy, radiotherapy, immunotherapy, or biological therapy for the treatment of breast cancer within 2 weeks of the first study treatment. Prior cumulative doxorubicin dose > 360 mg/m^2 or the equivalent. History of significant cardiac disease, unstable angina, congestive heart failure (CHF), myocardial infarction, or ventricular arrythmia requiring medication.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Trastuzumab emtansine 3.6 mg/kg<br>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. | Drug: Trastuzumab emtansine [Kadcyla]<br>* Trastuzumab emtansine was provided in either a liquid or a lyophilized formulation.<br>* Other names: T-DM1;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Assessed by the Independent Review Facility Using Response Evaluation Criteria in Solid Tumors (RECIST) | 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. | 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) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Objective Response (OR) Assessed by the Independent Review Facility Using Response Evaluation Criteria in Solid Tumors (RECIST) | 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. | 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) | 
| Progression-free Survival (PFS) Assessed by the Independent Review Facility Using Response Evaluation Criteria in Solid Tumors (RECIST) | 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. | 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) | 
| Objective Response Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST) | 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. | 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) | 
| Duration of Objective Response Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST) | 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. | 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) | 
| Progression-free Survival Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST) | 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. | 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Trastuzumab emtansine, MBC, Breast cancer, HER2-positive breast cancer, HER2