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