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

Metastatic Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00509769
• Other study ID #: TDM4258g
• Status: Completed
• Phase: Phase 2
• First received: July 27, 2007
• Last updated: February 22, 2013
• Start date: July 2007
• Est. completion date: June 2009

Study information

• Verified date: February 2013
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 112
• Est. completion date: June 2009
• Est. primary completion date: January 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

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 Design

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Neoplasms
• Metastatic Breast Cancer

Intervention

Drug:
• Trastuzumab emtansine [Kadcyla]
Trastuzumab emtansine was provided in either a liquid or a lyophilized formulation.

Locations

Country	Name	City	State
United States	New York Oncology Hematology	Albany	New York
United States	Texas Oncology Cancer Center	Austin	Texas
United States	Texas Oncology, P.A.	Bedford	Texas
United States	Lynn Cancer Institute - West	Boca Raton	Florida
United States	Eastchester Center/Cancer Care	Bronx	New York
United States	Carolinas Hem-Oncology Assoc	Charlotte	North Carolina
United States	Missouri Cancer Associates	Columbia	Missouri
United States	Cancer Specialists of South Te	Corpus Christi	Texas
United States	Sammons Cancer Center	Dallas	Texas
United States	Texas Oncology, P.A.	Dallas	Texas
United States	US Oncology Research, Inc.	Dallas	Texas
United States	USO	Dallas	Texas
United States	Florida Cancer Care	Davie	Florida
United States	Rocky Mountain Cancer Center	Denver	Colorado
United States	El Paso Cancer Treatment Ctr	El Paso	Texas
United States	Midwestern Regional Med Center	Eugene	Oregon
United States	Fairfax N Virginia Hem/Onc PC	Fairfax	Virginia
United States	Texas Oncology PA	Fort Worth	Texas
United States	John McClean, M.D. - Private P	Galesburg	Illinois
United States	Texas Oncology, P.A.	Houston	Texas
United States	Mayo Clinic	Jacksonville	Florida
United States	Kansas City Cancer Center, LLC	Lee's Summit	Missouri
United States	Little Rock Hem Onc Assoc	Little Rock	Arkansas
United States	St. Barnabas Health Care Sys	Livingston	New Jersey
United States	Kentuckiana Cancer Institute	Louisville	Kentucky
United States	Northwest Georgia Onc Ctrs PC	Marietta	Georgia
United States	US Oncology	Midland	Texas
United States	Minnesota Oncology Hematology,	Minneapolis	Minnesota
United States	Northern Utah Associates	Ogden	Utah
United States	Hem/Onc Assoc - Treasure Coast	Port St Lucie	Florida
United States	Raleigh Hemotology & Oncology	Raleigh	North Carolina
United States	St. Louis Cancer & Breast Inst	Saint Louis	Missouri
United States	Gulfcoast Oncology Associates	Saint Petersburg	Florida
United States	Northwest Medical Specialties	Tacoma	Washington
United States	Bay Area Oncology	Tampa	Florida
United States	USO - Tyler Cancer Ctr	Tyler	Texas
United States	Northwest Cancer Specialists	Vancouver	Washington
United States	Waco Cancer Care & Research Ce	Waco	Texas
United States	Washington Cancer Institute	Washington	District of Columbia
United States	Cedar Valley Med Specialists	Waterloo	Iowa

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No