A Phase II Study Of The Efficacy And Safety Of SU011248 In Patients With Anthracycline- And Taxane-Resistant Metastatic Breast Cancer

Inclusion Criteria

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