Trastuzumab Plus Paclitaxel in Treating Women With Metastatic Breast Cancer That Overexpresses HER2
Trastuzumab Plus Paclitaxel in Treating Women With Metastatic Breast Cancer That Overexpresses HER2
RATIONALE: Monoclonal antibodies, such as trastuzumab, can locate tumor cells and either kill
 them or deliver tumor-killing substances to them without harming normal cells. Drugs used in
 chemotherapy use different ways to stop tumor cells from dividing so they stop growing or
 die. Combining monoclonal antibody therapy with chemotherapy may kill more tumor cells.

 PURPOSE: Randomized phase II trial to study the effectiveness of two different regimens of
 trastuzumab plus paclitaxel in treating women who have metastatic breast cancer that
 overexpresses HER2.
OBJECTIVES: I. Evaluate the safety and tolerability of subcutaneous trastuzumab (Herceptin)
 plus paclitaxel in women with HER2 overexpressing metastatic breast cancer. II. Assess the
 activity of this treatment regimen in these patients. III. Determine the pharmacokinetics of
 trastuzumab and paclitaxel in this regimen.

 OUTLINE: This is a randomized, open label, multicenter study. Patients are randomized to one
 of two treatment arms. Patients receive a loading dose of trastuzumab (Herceptin) IV over 90
 minutes followed by paclitaxel IV over 3 hours on day 0. Paclitaxel is repeated every 3 weeks
 for 6 courses in the absence of disease progression or unacceptable toxicity. Arm I: Patients
 receive trastuzumab subcutaneously (SC) weekly starting day 7. Arm II: Patients receive
 trastuzumab SC twice weekly starting day 7. Treatment with trastuzumab SC continues for 48
 weeks in the absence of disease progression or unacceptable toxicity.

 PROJECTED ACCRUAL: A total of 80 patients (40 per treatment arm) will be accrued for this
 study.
DISEASE CHARACTERISTICS: HER2 overexpressing (3+) metastatic breast cancer by
 immunohistochemistry, or amplified by fluorescent in situ hybridization (FISH) No prior
 chemotherapy for breast cancer metastases No bilateral disease Bidimensionally measurable
 disease At least 1 target lesion greater than 1 cm2 No significant lymphedema in the arm
 ipsilateral to mastectomy site, unless patient has an indwelling catheter for the purpose
 of chemotherapy infusion No CNS metastases Hormone receptor status: Not specified

 PATIENT CHARACTERISTICS: Age: 18 and over Sex: Female Menopausal status: Not specified
 Performance status: Karnofsky 70-100% Life expectancy: Not specified Hematopoietic:
 Hemoglobin at least 9.0 g/dL WBC at least 3,000/mm3 Platelet count at least 100,000/mm3
 Granulocyte count at least 1,500/mm3 Hepatic: Bilirubin no greater than 1.5 times upper
 limit of normal (ULN) ALT, AST, and alkaline phosphatase no greater than 2.5 times ULN (no
 greater than 4.0 times ULN with liver or bone metastases) Renal: Creatinine no greater than
 1.5 times ULN Cardiovascular: No clinically significant cardiovascular disease (e.g.,
 uncontrolled hypertension, myocardial infarction, unstable angina, intractable arrhythmia,
 congestive heart failure, or New York Heart Association class II-IV heart disease) Left
 ventricular ejection fraction at least 50% or above lower limit of normal, whichever is
 lower Other: No severe hypersensitivity to products containing Cremophor EL (e.g.,
 cyclosporine or teniposide for injection concentrate) No other serious medical condition
 that would preclude study Not pregnant or nursing Negative pregnancy test Fertile patients
 must use effective contraception

 PRIOR CONCURRENT THERAPY: Biologic therapy: At least 14 days since prior immunotherapy No
 prior trastuzumab (Herceptin) No other concurrent immunotherapy Chemotherapy: See Disease
 Characteristics Prior cytotoxic chemotherapy allowed in adjuvant setting Prior cumulative
 doxorubicin exposure no greater than 300 mg/m2 At least 1 year since prior taxane therapy
 No other concurrent chemotherapy Endocrine therapy: At least 14 days since prior hormonal
 therapy No concurrent hormonal therapy (e.g., tamoxifen, megestrol acetate,
 fluoxymesterone, or aminoglutethimide) Radiotherapy: At least 14 days since prior
 radiotherapy No concurrent radiotherapy to target lesions Surgery: Not specified Other: At
 least 30 days since other prior investigational agent or procedure No other concurrent
 investigational agents