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

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

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).

Study Overview

• Status: Completed
• Conditions: Metastatic Breast Cancer
• Intervention / Treatment: Drug: Trastuzumab emtansine [Kadcyla]

• Study Type: Interventional
• Enrollment (Actual): 112
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Little Rock Hem Onc Assoc
  • Colorado
    • Denver, Colorado, United States, 80220
      • Rocky Mountain Cancer Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Washington Cancer Institute
  • Florida
    • Boca Raton, Florida, United States, 33428
      • Lynn Cancer Institute - West
    • Davie, Florida, United States, 33328
      • Florida Cancer Care
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic
    • Port St Lucie, Florida, United States, 34952
      • Hem/Onc Assoc - Treasure Coast
    • Saint Petersburg, Florida, United States, 33705
      • Gulfcoast Oncology Associates
    • Tampa, Florida, United States, 33607
      • Bay Area Oncology
  • Georgia
    • Marietta, Georgia, United States, 30060
      • Northwest Georgia Onc Ctrs PC
  • Illinois
    • Galesburg, Illinois, United States, 61401
      • John McClean, M.D. - Private P
  • Iowa
    • Waterloo, Iowa, United States, 50702
      • Cedar Valley Med Specialists
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Kentuckiana Cancer Institute
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Minnesota Oncology Hematology,
  • Missouri
    • Columbia, Missouri, United States, 65201
      • Missouri Cancer Associates
    • Lee's Summit, Missouri, United States, 64064
      • Kansas City Cancer Center, LLC
    • Saint Louis, Missouri, United States, 63141
      • St. Louis Cancer & Breast Inst
  • New Jersey
    • Livingston, New Jersey, United States, 07039
      • St. Barnabas Health Care Sys
  • New York
    • Albany, New York, United States, 12206
      • New York Oncology Hematology
    • Bronx, New York, United States, 10469
      • Eastchester Center/Cancer Care
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Carolinas Hem-Oncology Assoc
    • Raleigh, North Carolina, United States, 27607
      • Raleigh Hemotology & Oncology
  • Oregon
    • Eugene, Oregon, United States, 97401-8122
      • Midwestern Regional Med Center
  • Texas
    • Austin, Texas, United States, 78731
      • Texas Oncology Cancer Center
    • Bedford, Texas, United States, 76022
      • Texas Oncology, P.A.
    • Corpus Christi, Texas, United States, 78412
      • Cancer Specialists of South Te
    • Dallas, Texas, United States, 75231-4400
      • Texas Oncology, P.A.
    • Dallas, Texas, United States, 75246
      • Sammons Cancer Center
    • Dallas, Texas, United States, 75204
      • US Oncology Research, Inc.
    • Dallas, Texas, United States, 75230-2510
      • USO
    • El Paso, Texas, United States, 79915
      • El Paso Cancer Treatment Ctr
    • Fort Worth, Texas, United States, 76104
      • Texas Oncology PA
    • Houston, Texas, United States, 77024-2305
      • Texas Oncology, P.A.
    • Midland, Texas, United States, 79701
      • US Oncology
    • Tyler, Texas, United States, 75702
      • USO - Tyler Cancer Ctr
    • Waco, Texas, United States, 76712
      • Waco Cancer Care & Research Ce
  • Utah
    • Ogden, Utah, United States, 84403
      • Northern Utah Associates
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Fairfax N Virginia Hem/Onc PC
  • Washington
    • Tacoma, Washington, United States, 98405
      • Northwest Medical Specialties
    • Vancouver, Washington, United States, 98684
      • Northwest Cancer Specialists

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / 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: T-DM1; trastuzumab-DM1; trastuzumab-MCC-DM1

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Genentech, Inc.

Study record dates

Study Major Dates

• Study Start: July 1, 2007
• Primary Completion (Actual): January 1, 2009
• Study Completion (Actual): June 1, 2009

Study Registration Dates

• First Submitted: July 27, 2007
• First Submitted That Met QC Criteria: July 27, 2007
• First Posted (Estimate): July 31, 2007

Study Record Updates

• Last Update Posted (Estimate): April 2, 2013
• Last Update Submitted That Met QC Criteria: February 22, 2013
• Last Verified: February 1, 2013

More Information

Terms related to this study

• Keywords: HER2; Breast cancer; HER2-positive breast cancer; MBC; Trastuzumab emtansine
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Trastuzumab; Maytansine; Ado-Trastuzumab Emtansine
• Other Study ID Numbers: TDM4258g