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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.

Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Metastatic Breast Cancer Drug: Trastuzumab emtansine [Kadcyla] Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 112 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : July 2007
Actual Primary Completion Date : January 2009
Actual Study Completion Date : June 2009

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
U.S. FDA Resources

Arm Intervention/treatment
Experimental: Trastuzumab emtansine 3.6 mg/kg
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]
Trastuzumab emtansine was provided in either a liquid or a lyophilized formulation.
Other Names:
  • trastuzumab-DM1
  • trastuzumab-MCC-DM1
  • T-DM1



Primary Outcome Measures :
  1. Objective Response Assessed by the Independent Review Facility Using Response Evaluation Criteria in Solid Tumors (RECIST) [ 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) ]
    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.


Secondary Outcome Measures :
  1. Duration of Objective Response (OR) Assessed by the Independent Review Facility Using Response Evaluation Criteria in Solid Tumors (RECIST) [ 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) ]
    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.

  2. Progression-free Survival (PFS) Assessed by the Independent Review Facility Using Response Evaluation Criteria in Solid Tumors (RECIST) [ 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) ]
    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.

  3. Objective Response Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST) [ 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) ]
    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.

  4. Duration of Objective Response Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST) [ 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) ]
    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.

  5. Progression-free Survival Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST) [ 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) ]
    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.



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Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00509769


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Sponsors and Collaborators
Genentech, Inc.
Investigators
Study Director: Scott Holden, M.D. Genentech, Inc.

Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT00509769     History of Changes
Other Study ID Numbers: TDM4258g
First Posted: July 31, 2007    Key Record Dates
Results First Posted: April 2, 2013
Last Update Posted: April 2, 2013
Last Verified: February 2013

Keywords provided by Genentech, Inc.:
Trastuzumab emtansine
MBC
Breast cancer
HER2-positive breast cancer
HER2

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Ado-trastuzumab emtansine
Trastuzumab
Maytansine
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic