RATIONALE: SU011248 may stop the growth of tumor cells by blocking the enzymes necessary for their growth and by stopping blood flow to the tumor.

PURPOSE: Phase II trial to study the effectiveness of SU012248 in treating women who have metastatic breast cancer that did not respond to previous chemotherapy that included drugs such as daunorubicin, doxorubicin, epirubicin, docetaxel, or paclitaxel.

Condition	Treatment or Intervention	Phase
stage IV breast cancer recurrent breast cancer	Drug: SU011248  Procedure: anti-cytokine therapy  Procedure: antiangiogenesis therapy  Procedure: biological response modifier therapy  Procedure: enzyme inhibitor therapy  Procedure: growth factor antagonist therapy  Procedure: protein tyrosine kinase inhibitor therapy	Phase II

Further Study Details: 

OBJECTIVES: Primary

• Determine the antitumor efficacy of SU011248, in terms of objective response rate (confirmed complete or partial response), in women with anthracycline- or taxane-resistant metastatic breast cancer.

Secondary

• Determine the duration of tumor control and 1-year survival rate of patients treated with this drug.
• Determine the safety of this drug in these patients.
• Correlate plasma concentrations of this drug with efficacy and safety parameters in these patients.
• Correlate potential cancer biomarkers with cancer- and treatment-related outcomes in patients treated with this drug.

OUTLINE: This is an open-label, multicenter study.

Patients receive oral SU011248 once daily on days 1-28. Courses repeat every 42 days for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients may then continue to receive SU011248 on this protocol or a separate continuation protocol.

Patients are followed at 1 month and then every 2 months for 1 year.

PROJECTED ACCRUAL: A total of 38-63 patients will be accrued for this study.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

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 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

California
      Jonsson Comprehensive Cancer Center, UCLA, Los Angeles,  California,  90095-1781,  United States; Recruiting

Study chairs or principal investigators

Mark D. Pegram, MD,  Study Chair,  Jonsson Comprehensive Cancer Center   

Study ID Numbers:  CDR0000393973; UCLA-0402087-01; PFIZER-A6181002; PFIZER-PHA-RTKC-0511; NCT00095615
Record last reviewed:  October 2004
Last Updated:  February 4, 2005
Record first received:  November 5, 2004
ClinicalTrials.gov Identifier:  NCT00095615
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08