Chemotherapy Plus Trastuzumab in Treating Patients With Breast Cancer

OBJECTIVES:

• Determine the maximum tolerated dose of vinorelbine in combination with trastuzumab (Herceptin) in patients with HER-2/neu overexpressing unresectable or metastatic non-small cell lung cancer (closed to accrual as of 4/16/01) or refractory locally advanced or metastatic breast cancer.
• Determine the pharmacokinetic and pharmacodynamic profiles of this regimen in this patient population.
• Determine the objective response rate of patients treated with this regimen.

OUTLINE: This is a dose-escalation study of vinorelbine.

Patients receive vinorelbine IV over 5-10 minutes on days 1 and 8, and trastuzumab (Herceptin) IV over 30-90 minutes on days 8 and 15 of course 1 and days 1, 8, and 15 of all subsequent courses. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3 to 6 patients receive escalating doses of vinorelbine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 6 patients experience dose-limiting toxicity.

PROJECTED ACCRUAL: Approximately 30-35 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed unresectable or metastatic non-small cell lung cancer

• Stage IIIB or IV (closed to accrual as of 4/16/01) OR
• Histologically confirmed locally advanced breast cancer that has progressed after first-line chemotherapy or metastatic breast cancer
• HER-2/neu overexpression (1+ to 3+)
• Hormone receptor status:

• Not specified

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Menopausal status:

• Not specified

Performance status:

• Karnofsky 60-100%

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count at least 2,000/mm3
• Platelet count at least 100,000/mm3

Hepatic:

• Bilirubin no greater than 2 times upper limit of normal (ULN)
• ALT no greater than 3 times ULN

Renal:

• Creatinine no greater than 2 times ULN

Cardiovascular:

• No prior or concurrent unstable angina
• No prior symptomatic congestive heart failure
• No myocardial infarction within the past 6 months
• LVEF at least 45% by echocardiogram or MUGA if received prior anthracycline or anthrapyrazole therapy

Other:

• No prior hypersensitivity to trastuzumab, Chinese hamster ovary cell proteins, or any component of these products
• No other medical illness that would preclude study
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior trastuzumab (Herceptin)

Chemotherapy:

• See Disease Characteristics
• No prior vinorelbine

Endocrine therapy:

• Not specified

Radiotherapy:

• Not specified

Surgery:

• Not specified