A Safety and Efficacy Study of Doxil and Taxotere +/- Herceptin in Advanced Breast Cancer
I. Assess the safety, toxicity, and feasibility of doxorubicin hydrochloride (HCL) liposome
and docetaxel with or without trastuzumab (Herceptin™) in patients with metastatic breast
cancer, particularly with respect to cardiotoxicity.
II. Assess the overall objective response rate, response duration, time to treatment
failure, and median survival of these patients with these treatment regimens.
III. Assess any association between trough plasma levels of cardiac troponin T and brain
natriuretic peptide and any cardiac event (congestive heart failure or left ventricular
ejection fraction decrease).
OUTLINE: Patients are assigned to one of two treatment arms according to HER2 overexpression
Arm I (HER2 nonoverexpressed): Patients receive doxorubicin hydrochloride liposome IV over
30 minutes followed by docetaxel IV over 1 hour. Treatment is repeated every 3 weeks for 8
courses in the absence of disease progression or unacceptable toxicity.
Patients may receive maintenance therapy of docetaxel IV over 1 hour either weekly or every
3 weeks. Maintenance continues in the absence of disease progression or unacceptable
Arm II (HER2 overexpressed): Patients receive trastuzumab IV over 90 minutes on day 1, with
subsequent doses over 30 minutes. Patients receive doxorubicin HCl liposome IV over 30
minutes followed by docetaxel IV over 1 hour on day 2 of course 1, followed by subsequent
doses on day 1 of each course. Antibody therapy continues weekly and chemotherapy every 3
weeks for 8 courses.
Patients may receive maintenance therapy of trastuzumab IV over 30 minutes weekly followed
by docetaxel IV over 1 hour weekly or every 3 weeks. Maintenance continues in the absence of
disease progression or unacceptable toxicity.
Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Grades of Cardiotoxicity Events in the Subset of Patients Reporting a Cardiotoxicity Event
This table summarizes the cardiotoxicity events of different grades. Grade 1 is a decline of left ventricular ejection fraction(LVEF) >=10% but <20% of baseline value. Grade 2 is LVEF below LLN (50%) or decline of LVEF >=20% of baseline value. Grade 3 is congestive heart failure responsive to treatment. Please note that only a subset of patients reported cardiotoxic events so the totals will not add up to the total number of participants.
Baseline, after cycle 4 (~84 days), after cycle 8 (~168 days), and 30 or more days after last cycle of induction therapy
Antonio C. Wolff, MD
The Johns Hopkins Oncology Center Cancer Research Building
United States: Federal Government
|CCOP - Carle Cancer Center||Urbana, Illinois 61801|
|CCOP - Iowa Oncology Research Association||Des Moines, Iowa 50309-1016|
|CCOP - Kalamazoo||Kalamazoo, Michigan 49007-3731|
|CCOP - Metro-Minnesota||Saint Louis Park, Minnesota 55416|
|West Michigan Cancer Center||Kalamazoo, Michigan 49007-3731|
|CCOP - Duluth||Duluth, Minnesota 55805|
|Penn State Cancer Institute at Milton S. Hershey Medical Center||Hershey, Pennsylvania 17033-0850|
|CCOP - Merit Care Hospital||Fargo, North Dakota 58122|
|CCOP - Sioux Community Cancer Consortium||Sioux Falls, South Dakota 57105-1080|
|CCOP - Columbus||Columbus, Ohio 43206|
|CCOP - MainLine Health||Wynnewood, Pennsylvania 19096|
|CCOP - Northern Indiana CR Consortium||South Bend, Indiana 46601|
|MetroHealth's Cancer Care Center at MetroHealth Medical Center||Cleveland, Ohio 44106|
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins||Baltimore, Maryland 21231-2410|
|CCOP - St. Vincent Hospital Cancer Center, Green Bay||Green Bay, Wisconsin 54301|
|Albert Einstein Clinical Cancer Center||Bronx, New York 10461|
|Tufts - New England Medical Center||Boston, Massachusetts 02111|
|Winship Cancer Institute of Emory University||Atlanta, Georgia 30322|
|CCOP - Marshfield Clinic Research Foundation||Marshfield, Wisconsin 54449|
|Cancer Institute of New Jersey at Robert Wood Johnson University Hospital||New Brunswick, New Jersey 08903|
|MBCCOP-Our Lady of Mercy Cancer Center||Bronx, New York 10466|
|Robert H. Lurie Comprehensive Cancer Center at Northwestern University||Chicago, Illinois 60611|
|Lankenau Cancer Center at Lankenau Hospital||Wynnewood, Pennsylvania 19096|