GW572016 and Trastuzumab in Treating Patients With Metastatic Breast Cancer That Overexpresses HER2/Neu

• Histologically or cytologically confirmed breast cancer
• Metastatic disease
• Measurable or evaluable disease
• HER2/neu overexpression (2+ or 3+) confirmed by immunohistochemistry and/or HER2 gene amplification by fluorescence in situ hybridization

• Brain metastases treated by surgery and/or radiotherapy allowed provided the following criteria are met:

  • Neurologic status stable 2 weeks after discontinuing dexamethasone
  • No concurrent anticonvulsants that induce metabolism (e.g., phenytoin, carbamazepine, or phenobarbital)
• 18 and over
• Male or female
• Karnofsky 70-100%
• Life expectancy, At least 12 weeks

• Hematopoietic

  • Absolute granulocyte count ≥ 1,500/mm\^3
  • Platelet count ≥ 100,000/mm\^3
  • Hemoglobin ≥ 9 g/dL
  • AST and ALT ≤ 3 times upper limit of normal (ULN) (5 times ULN if patient has liver metastases)
  • Bilirubin \< 1.5 mg/dL
  • Creatinine clearance > 30 mL/min

• Cardiovascular

  • LVEF > 50%
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 4 weeks after study participation
• Adequate venous access
• Able to swallow and retain oral medication
• Prior adjuvant/neoadjuvant chemotherapy allowed
• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin.
• More than 4 weeks since prior radiotherapy
• More than 4 weeks since prior major surgery
• Recovered from all prior therapy
• More than 28 days since prior participation in another investigational study
• More than 28 days since prior investigational drugs

Exclusion Criteria:

• extensive tumor, pleural effusions, or parenchymal masses) resulting in dyspnea at rest
• uncontrolled brain metastases or leptomeningeal disease
• prior myocardial infarction
• pre-existing cardiac dysfunction (e.g., congestive heart failure)
• clinically significant cardiac disease
• angina pectoris
• symptomatic intrinsic pulmonary disease (e.g., asthma or chronic obstructive pulmonary disease) resulting in dyspnea at rest
• pregnant or nursing
• active infection
• known hypersensitivity to Chinese Hamster Ovary cell proteins or any component of this product
• known immediate or delayed hypersensitivity reaction or idiosyncrasy to products of similar chemical composition as study drug
• known contraindications to trastuzumab (Herceptin\^®)
• malabsorption syndrome
• disease significantly affecting gastrointestinal function
• psychiatric disorder that would preclude study compliance
• other serious illness or condition
• concurrent biologic therapy
• prior cumulative dose of doxorubicin > 400 mg/m\^2 (including liposomal doxorubicin)
• concurrent hormonal therapy*
• concurrent glucocorticoids
• concurrent radiotherapy
• prior major resection of the stomach or small bowel that could affect absorption of GW572016
• concurrent cytotoxic therapy
• other concurrent anticancer therapy
• other concurrent investigational drugs during and for 28 days after study treatment
• concurrent administration of any of the following medications or substances:

• Antibiotics

  • Clarithromycin
  • Erythromycin
  • Troleandomycin
  • Ciprofloxacin
  • Rifampin
  • Norfloxacin
  • Rifabutin

• HIV antivirals

  • Delaviridine
  • Indinavir
  • Nelfinavir
  • Ritonavir
  • Saquinavir
  • Efavirenz
  • Nevirapine
  • Amprenavir
  • Lopinavir

• Anticonvulsants

  • Phenytoin
  • Carbamazepine
  • Phenobarbital

• Antidepressants

  • Fluoxetine
  • Nefazodone
  • Fluvoxamine

• Antifungals

  • Itraconazole
  • Ketoconazole
  • Fluconazole
  • Voriconazole
• Antacids (within 1 hour before and after study drug administration)
• Cimetidine
• Amiodarone
• Diltiazem
• Pioglitazone
• Hypericum perforatum (St. John's wort)
• Grapefruit or grapefruit juice
• Rifabutin
• Diethyldithiocarbamate
• Gestodene
• Mifepristone
• Modafinil