Tipifarnib Plus Trastuzumab in Treating Patients With Metastatic Breast Cancer

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed metastatic adenocarcinoma of the breast

  • HER2/neu 3+ by immunohistochemical staining

    • 2+ eligible provided HER2/neu positive by fluorescent in-situ hybridization (FISH)
    • HER2/neu positive by FISH alone allowed

• Unidimensionally measurable disease

  • At least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan
• Must have received prior trastuzumab (Herceptin)

• Patients with known brain metastases meeting any of the following criteria are not eligible:

  • Require high-dose steroid therapy or enzyme-inducing anticonvulsant drugs
  • No prior cranial radiotherapy
  • Have progressive neurologic dysfunction that would preclude study evaluation
  • Have evidence of progressive CNS disease by CT scan or MRI

• Hormone receptor status:

  • Not specified

PATIENT CHARACTERISTICS:

Age

• Over 18

Sex

• Male or female

Menopausal status

• Not specified

Performance status

• ECOG 0-2 OR
• Karnofsky 70-100%

Life expectancy

• At least 12 weeks

Hematopoietic

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 9.0 g/dL

Hepatic

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

Renal

• Creatinine no greater than 1.5 times ULN OR
• Creatinine clearance greater than 60 mL/min

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia
• Ejection fraction greater than 50% by MUGA or echocardiogram

Gastrointestinal

• No gastrointestinal tract disease resulting in an inability to tolerate oral medication
• No requirement for IV alimentation
• No active peptic ulcer disease

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No significant traumatic injury within the past 21 days
• No other malignancy within the past 3 years except nonmelanoma skin cancer or carcinoma in situ of the cervix
• No ongoing or active infection
• No prior allergic reaction attributed to compounds of similar chemical or biological composition to tipifarnib (e.g., quinolones) or trastuzumab
• No psychiatric illness or social situation that would preclude study compliance
• No other concurrent medical illness that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics
• No prior bone marrow transplantation with high-dose chemotherapy
• No concurrent immunotherapy

Chemotherapy

• See Biologic therapy
• No more than 2 prior chemotherapy regimens for metastatic disease

• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered

  • Prior combination chemotherapy allowed
• No concurrent chemotherapy

Endocrine therapy

• See Disease Characteristics
• Prior hormonal therapy allowed
• No concurrent hormonal therapy for cancer

Radiotherapy

• See Disease Characteristics
• More than 4 weeks since prior wide-field radiotherapy and recovered
• No concurrent radiotherapy

Surgery

• Prior modified radical mastectomy or lumpectomy with axillary node dissection allowed
• Prior resection of metastatic lesions allowed
• More than 21 days since prior major surgery
• No prior surgery affecting absorption

Other

• No prior tipifarnib
• More than 6 weeks since initiation of bisphosphonate therapy (if bone lesions are the only site of measurable disease)
• Bisphosphonate therapy may not be initiated during study
• No other concurrent investigational agents
• No other concurrent anticancer therapy
• No concurrent antacids within 2 hours of study drug