Patient case: 49-year-old female with lung cancer; genetic feature: ERBB2

Clinical trial: Chemotherapy Plus Trastuzumab in Treating Patients With Breast Cancer

Summary: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells.
  PURPOSE: Phase I trial to study the effectiveness of vinorelbine plus trastuzumab in treating patients who have refractory or metastatic breast cancer.

Detailed description: 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.

Eligibility: 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

Relevance to patient case: definitely relevant