Lonafarnib, Trastuzumab, and Paclitaxel in Treating Patients With HER2/Neu-Overexpressing Stage IIIB, Stage IIIC, or Stage IV Breast Cancer

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed breast cancer

  • Stage IIIB, IIIC, or IV

• HER2/neu overexpression

  • 3+ by immunohistochemistry

    • 2+ allowed if positive fluorescent in situ hybridization

• Disease meets the following treatment criteria:

  • Paclitaxel/trastuzumab (Herceptin®) may be appropriate therapy
  • Anthracycline therapy is not a suitable approach
• No clinical signs of CNS involvement

• Hormone receptor status:

  • Not specified

PATIENT CHARACTERISTICS:

Age

• 18 and over

Sex

• Male or female

Menopausal status

• Not specified

Performance status

• ECOG 0-2 OR
• WHO 0-2

Life expectancy

• Not specified

Hematopoietic

• Neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 10.0 g/dL (6.2 mmol/L)

Hepatic

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• Alkaline phosphatase less than 2.5 times ULN (5 times ULN if liver metastases are present)
• AST and ALT less than 2.5 times ULN (5 times ULN if liver metastases are present)

Renal

• Creatinine clearance at least 40 mL/min

Cardiovascular

• Cardiac ejection fraction normal by MUGA
• QTc interval no greater than 440 msec
• No cardiac dysfunction

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for up to 3 months after study participation
• No concurrent severe/unstable systemic disease
• No infection
• No circumstances that would preclude study participation (e.g., alcoholism or substance abuse)
• No psychological, familial, sociological, or geographical condition that would preclude study compliance and follow-up

PRIOR CONCURRENT THERAPY:

Biologic therapy

• More than 1 year since prior trastuzumab
• No concurrent prophylactic growth factors

Chemotherapy

• More than 1 year since prior paclitaxel
• More than 4 weeks since other prior chemotherapy

Endocrine therapy

• More than 1 day since prior hormonal therapy
• More than 2 days since prior high-dose chronic steroids
• More than 2 days since prior ethinyl estradiol
• No concurrent high-dose chronic steroids
• No concurrent ethinyl estradiol

Radiotherapy

• More than 4 weeks since prior radiotherapy

Surgery

• Not specified

Other

• More than 2 days since prior administration of and no concurrent CYP3A4 inducers or inhibitors, including any of the following:

  • Gestodene
  • Itraconazole
  • Ketoconazole
  • Cimetidine
  • Erythromycin
  • Carbamazepine
  • Phenobarbital
  • Phenytoin
  • Rifampin
  • Sulfinpyrazone
• No concurrent grapefruit juice
• No other concurrent anticancer agents
• No other concurrent investigational therapy