SU011248 in Treating Women With Metastatic Breast Cancer That Did Not Respond to Anthracycline or Taxane Chemotherapy

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed breast adenocarcinoma

  • Metastatic disease
• Not amenable to surgery, radiotherapy, or combined modality therapy with curative intent

• Anthracycline-resistant OR taxane-resistant disease, defined as relapse or disease progression during treatment or within 12 months after completion of an anthracycline or a taxane

  • Received both a prior anthracycline-based and a prior taxane-based chemotherapy regimen either concurrently or sequentially in the adjuvant and/or advanced disease treatment setting

• Measurable disease, defined as ≥ 1 unidimensional lesion ≥ 20 mm by conventional radiographic techniques or MRI OR ≥ 10-16 mm by spiral CT scan (depending on interval)

  • Positron emission tomography or ultrasound may not be substituted for MRI or CT scan

  • The following are not considered measurable disease:

    • Bone lesions
    • Ascites
    • Peritoneal carcinomatosis
    • Miliary lesions
    • Pleural or pericardial effusions
    • Lymphangitis of the skin or lung
    • Cystic lesions
    • Irradiated lesions
    • Disease documented by indirect evidence only (e.g., by laboratory tests such as alkaline phosphatase)
• No known brain metastases or carcinomatous meningitis
• No new evidence of brain or leptomeningeal disease on screening CT scan or MRI
• No spinal cord compression

• Hormone receptor status:

  • Not specified

PATIENT CHARACTERISTICS:

Age

• 18 and over

Sex

• Female

Menopausal status

• Not specified

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

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

Hepatic

• AST and ALT ≤ 2.5 times upper limit of normal (ULN) (5 times ULN if due to liver metastases)
• Bilirubin ≤ 1.5 times ULN
• PT and PTT ≤ 1.5 times ULN
• Albumin ≥ 3.0 g/dL

Renal

• Creatinine ≤ 1.5 times ULN

Cardiovascular

• LVEF ≥ 10% above lower limit of normal by MUGA

• None of the following within the past year:

  • Myocardial infarction
  • Severe or unstable angina
  • Symptomatic congestive heart failure
  • Cerebrovascular accident or transient ischemic attack
  • Deep vein thrombosis
  • Other thromboembolic event
• No ongoing cardiac dysrhythmias ≥ grade 2
• No atrial fibrillation of any grade
• No prolongation of the QTc interval to > 470 msec

Pulmonary

• No pulmonary embolism within the past year

Other

• Adrenocorticotrophic hormone-stimulation test normal
• Amylase and lipase normal
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
• No other severe acute or chronic medical or psychiatric condition or laboratory abnormality that would preclude study participation
• No known HIV infection or AIDS-related illness
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 30 days after study treatment

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Chemotherapy
• Recovered from prior cytokine therapy
• Prior immunotherapy in the adjuvant and/or advanced/metastatic disease setting allowed
• At least 3 weeks since prior immunotherapy
• No other concurrent vascular endothelial growth factor inhibitors or angiogenic inhibitors
• No concurrent biologic response modifiers
• No concurrent immunotherapy

Chemotherapy

• See Disease Characteristics
• No prior non-anthracycline non-taxane chemotherapy agent in the advanced/metastatic disease setting
• No prior chemoembolization to only site of measurable disease
• At least 3 weeks since prior chemotherapy
• No prior high-dose-chemotherapy requiring hematopoietic stem cell rescue
• No concurrent chemotherapy

Endocrine therapy

• Prior hormonal therapy in the adjuvant and/or advanced/metastatic disease setting allowed
• At least 3 weeks since prior hormonal therapy
• No concurrent hormonal therapy

Radiotherapy

• No prior radiotherapy to only site of measurable disease
• At least 3 weeks since prior radiotherapy and recovered
• No prior radiotherapy to > 25% of the bone marrow
• Concurrent palliative radiotherapy allowed provided measurable lesions are outside the irradiated field

Surgery

• Recovered from prior surgery
• No prior surgery to only site of measurable disease
• More than 1 year since prior coronary or peripheral artery bypass graft
• No concurrent surgery to only site of measurable disease

Other

• No prior cryotherapy to only site of measurable disease
• Concurrent bisphosphonate therapy allowed for metastatic bone disease provided treatment was initiated at least 3 months before study entry
• No other concurrent tyrosine kinase inhibitors
• No concurrent treatment on another clinical trial
• No concurrent drugs with dysrhythmic potential (e.g., terfenadine, quinidine, procainamide, disopyramide, sotalol, probucol, bepridil, haloperidol, risperidone, or indapamide)
• No concurrent ketoconazole
• No other concurrent approved or investigational anticancer therapy