A Randomized, Open-Label, Phase III Study of Taxane Based Chemotherapy With Lapatinib or Trastuzumab as First-Line Therapy for Women With HER2/Neu Positive Metastatic Breast Cancer
- To compare the progression-free survival of women with HER2/neu-positive metastatic
breast cancer treated with taxane-based chemotherapy in combination with lapatinib
ditosylate or trastuzumab (Herceptin®).
- To compare the overall survival.
- To compare the time to CNS metastases at the time of first progression.
- To compare the incidence rates of CNS metastases at the time of progression.
- To compare the overall objective response rate (complete or partial response), time to
response, and duration of response in patients with measurable disease at baseline.
- To compare the clinical benefit response rate.
- To compare the adverse event profile.
- To compare the quality of life.
- To compare clinical outcomes using biomarker changes in biological samples.
- To compare health economics, including healthcare utilization and health utilities.
OUTLINE: This is a multicenter study. Patients are stratified according to prior
neoadjuvant/adjuvant anti-HER2/neu-targeted therapy (yes vs no), prior neoadjuvant/adjuvant
taxane chemotherapy (yes vs no), planned taxane therapy (paclitaxel vs docetaxel), and liver
metastasis (yes vs no). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive either paclitaxel IV on days 1, 8, and 15; treatment with
paclitaxel repeats every 4 weeks for 6 courses in the absence of disease progression or
unacceptable toxicity. Alternatively, patients may receive docetaxel IV on day 1;
treatment with docetaxel repeats every 3 weeks for 8 courses. Patients on docetaxel
also receive filgrastim (G-CSF) according to institutional standard. All patients
receive oral lapatinib ditosylate once daily during taxane treatment and continue after
completion of taxane treatment, in the absence of disease progression or unacceptable
- Arm II: Patients receive paclitaxel IV on days 1, 8, and 15 and trastuzumab
(Herceptin®) IV on days 1, 8, 15, and 22. Treatment repeats every 4 weeks for 6 courses
in the absence of disease progression or unacceptable toxicity. Alternatively, patients
may receive docetaxel IV and trastuzumab IV on day 1. Treatment repeats every 3 weeks
for 8 courses in the absence of disease progression or unacceptable toxicity. After
completion of taxane chemotherapy and trastuzumab, all patients receive trastuzumab
alone IV once every 3 weeks in the absence of disease progression or unacceptable
Formalin-fixed paraffin-embedded tissue samples are analyzed for ER, PgR, EGFR, CK5/6, Ki67,
and other molecular biomarkers by tissue microarray and immunohistochemistry.
Patients complete quality of life questionnaires (EORTC QLQ-C30 and a Trial Specific
Checklist) at baseline, every 12 weeks for 96 weeks, and then every 24 weeks until disease
After completion of study treatment, patients are followed at 4 weeks post treatment, and
then every 12 weeks thereafter (counting from the beginning of study therapy).
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Karen A. Gelmon, MD
British Columbia Cancer Agency
United States: Food and Drug Administration
|Advocate Christ Medical Center||Oak Lawn, Illinois 60453|
|Bozeman Deaconess Hospital||Bozeman, Montana 59715|
|Denver Health Medical Center||Denver, Colorado 80204-4507|
|Penrose Cancer Center||Colorado Springs, Colorado 80933|
|Cancer Care Center||New Albany, Indiana 47150|
|Arizona Clinical Research Center||Tucson, Arizona 85712|
|University of Washington||Seattle, Washington 98195|
|Genesis Cancer Center||Hot Springs, Arkansas 71913|
|South Carolina Oncology Associates||Columbia, South Carolina 29201|
|Greenwich Hospital - Bendheim Cancer Center||Greenwich, Connecticut 06830|
|Saint Joseph Medical Center, Cancer Care Program||Towson, Maryland 21204|
|Cascade Cancer Center||Kirkland, Washington 98034-3013|
|Osceola Cancer Center||Kissimmee, Florida 34741|
|Creticos Cancer Center||Chicago, Illinois 60657|
|Florida Cancer Institute||New Port Richey, Florida 34652|
|Kaiser Permanente||Portland, Oregon 97227|
|The West Clinic||Memphis, Tennessee 38120|
|Suburban Hematology-Oncology||Snellville, Georgia 30078-6782|
|Multicare Health System||Tacoma, Washington 98415|
|Clinical Trials and Research Associates, Inc.||Montebello, California 60460|
|Hematology Oncology P.C.||Stamford, Connecticut 06902-3628|
|Medical Oncology and Hematology||Waterbury, Connecticut 06708|
|Augusta Oncology Associates, PC||Augusta, Georgia 30901|
|Kootenai Cancer Center||Post Falls, Idaho 83854|
|Skagit Valley Hospital||Mt. Vernon, Washington 98273|
|Summit Cancer Care||Savannah, Georgia 31405|
|Cancer Specialists of Tidewater, Ltd.||Chesapeake, Virginia 23320|
|Cancer Center of Central Connecticut||Southington, Connecticut|
|St. Francis Medical Center||Grand Island, Nebraska 68803|
|Katmai Oncology Associates||Anchorage, Alaska 99508|
|Alta Bates Comprehensive Cancer Centre||Berkeley, California 94704|
|Oncology Association of Bridgeport-Bridgeport-US||Trumbull, Connecticut 06611|
|Oncology and Hematology Associates of Palm Beach||Lake Worth, Florida 33461|
|St. Francis Hospital and Health Centres||Beech Grove, Indiana 46107|
|Deaconess Clinic, Inc.||Evansville, Indiana 47713|
|IU Health Goshen Center for Cancer Care||Goshen, Indiana 46526|
|Community Hospital - Munster||Munster, Indiana 46321|
|Holy Cross Hospital Cancer Research||Silver Spring, Maryland 20902|
|Heartland Hematology and Oncology||Kearney, Nebraska 68845|
|Platte Valley Medical Group||Kearney, Nebraska 68847|
|Saint Clares Hospital Oncology and Hematology||Denville, New Jersey 7834|
|Saint Clares Health System at Parsippany Commons||Parsippany, New Jersey 07054|
|NY Medical College||Valhalla, New York 10595|
|Moses Cone Health System - Regional Cancer Center||Greensboro, North Carolina 27403|
|Tri-County Hematology and Oncology Specialists||Canton, Ohio 44718|
|Lawrence M. Stallings, MD, Ltd.||Wooster, Ohio 44691|
|Blue Ridge Cancer Centre||Salem, Virginia 24153|
|Overlake Internal Medicine Associates||Bellevue, Washington 98004|
|Olympic Medical Cancer Center Olympic Medical Park||Sequim, Washington 98382|