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

PURPOSE: This phase II trial is studying how well sorafenib works in treating patients with metastatic breast cancer.

Condition	Treatment or Intervention	Phase
stage IV breast cancer recurrent breast cancer Male Breast Cancer	Drug: sorafenib  Procedure: anti-cytokine therapy  Procedure: antiangiogenesis therapy  Procedure: biological response modifier therapy  Procedure: enzyme inhibitor therapy  Procedure: growth factor antagonist therapy	Phase II

Further Study Details: 

OBJECTIVES:

• Determine the tumor response rate in patients with metastatic breast cancer previously treated with an anthracycline- and/or taxane-containing regimen receiving sorafenib.
• Assess the toxicity profile of this drug in these patients.
• Determine time to disease progression and survival time of patients treated with this drug.
• Correlate pre-treatment levels of activated ERK1/2 with tumor response in patients treated with this drug.

OUTLINE: This is a multicenter study.

Patients receive oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients are followed every 6 months until disease progression and then every 3 months for up to 5 years.

PROJECTED ACCRUAL: A total of 20-42 patients will be accrued for this study within 5-18 months.

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

Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed breast cancer
• Clinical evidence of metastatic disease
• Measurable disease
• At least 1 lesion with longest diameter ≥ 20 mm by CT scan or MRI OR ≥ 10 mm by spiral CT scan
• HER2-positive or -negative disease
• If HER2 gene amplified or strongly positive for HER2 by immunohistochemistry, patient must have had prior treatment containing trastuzumab (Herceptin®) unless contraindicated
• Previously treated with anthracycline- and/or taxane-containing regimen in the neoadjuvant, adjuvant, or metastatic setting
• No more than 2 prior chemotherapy regimens, including neoadjuvant and adjuvant therapy
• No more than 1 prior chemotherapy regimen for metastatic disease
• Candidate for first- or second-line chemotherapy for metastatic disease
• Core block or tumor slides of the primary or metastatic tumor available
• No known brain metastases
• Hormone receptor status:
• Not specified

PATIENT CHARACTERISTICS: Age

• 18 and over

Sex

• Male or female

Menopausal status

• Not specified

Performance status

• ECOG 0-1

Life expectancy

• At least 3 months

Hematopoietic

• WBC ≥ 3,000/mm^3
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 8.5 g/dL
• No evidence of bleeding diathesis

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST ≤ 3 times ULN
• Alkaline phosphatase ≤ 3 times ULN
• PT normal
• PTT normal
• INR normal

Renal

• Creatinine ≤ 1.5 times ULN
• Calcium normal

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia
• No uncontrolled hypertension

Gastrointestinal

• No gastrointestinal tract disease that would preclude taking oral medication
• No active peptic ulcer disease

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer
• No history of allergic reaction attributed to compounds of similar chemical or biological composition to sorafenib or other study agents
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study participation
• No other uncontrolled illness

PRIOR CONCURRENT THERAPY: Biologic therapy

• See Disease Characteristics
• More than 4 weeks since prior immunotherapy
• No concurrent anticancer immunotherapy
• No concurrent bevacizumab

Chemotherapy

• See Disease Characteristics
• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
• No concurrent anticancer chemotherapy

Endocrine therapy

• Prior hormonal therapy in the neoadjuvant, adjuvant, or metastatic setting is allowed
• No concurrent anticancer hormonal therapy

Radiotherapy

• No prior radiotherapy to ≥ 25% of the bone marrow
• More than 4 weeks since prior radiotherapy

Surgery

• More than 4 weeks since prior major surgery
• No prior surgical procedure that would affect gastrointestinal absorption

Other

• No other concurrent drugs that target vascular endothelial growth factor (VEGF) or VEGF receptors
• No concurrent antiretroviral therapy for HIV-positive patients
• No other concurrent investigational agents
• No other concurrent anticancer therapy
• No concurrent cytochrome P450 enzyme-inducing antiepileptic drugs, including any of the following:
• Phenytoin
• Carbamazepine
• Phenobarbital
• No concurrent rifampin
• No concurrent Hypericum perforatum (St. John's wort)
• No concurrent therapeutic anticoagulation
• Concurrent prophylactic anticoagulation (i.e., low-dose warfarin) for venous or arterial devices is allowed

Alabama
      MBCCOP - Gulf Coast, Mobile,  Alabama,  36607,  United States; Recruiting
Arizona
      CCOP - Mayo Clinic Scottsdale Oncology Program, Scottsdale,  Arizona,  85259-5404,  United States; Recruiting
District of Columbia
      MBCCOP - Howard University Cancer Center, Washington,  District of Columbia,  20060,  United States; Recruiting
Florida
      Mayo Clinic - Jacksonville, Jacksonville,  Florida,  32224,  United States; Recruiting
Georgia
      CCOP - Atlanta Regional, Atlanta,  Georgia,  30342-1701,  United States; Recruiting
Hawaii
      MBCCOP - Hawaii, Honolulu,  Hawaii,  96813,  United States; Recruiting
Illinois
      CCOP - Carle Cancer Center, Urbana,  Illinois,  61801,  United States; Recruiting
      CCOP - Illinois Oncology Research Association, Peoria,  Illinois,  61615-7828,  United States; Recruiting
Iowa
      CCOP - Cedar Rapids Oncology Project, Cedar Rapids,  Iowa,  52403-1206,  United States; Recruiting
      CCOP - Iowa Oncology Research Association, Des Moines,  Iowa,  50309-1016,  United States; Recruiting
      Siouxland Hematology-Oncology, Sioux City,  Iowa,  51101-1733,  United States; Recruiting
Kansas
      CCOP - Wichita, Wichita,  Kansas,  67214-3882,  United States; Recruiting
Louisiana
      CCOP - Ochsner, New Orleans,  Louisiana,  70121,  United States; Recruiting
Michigan
      CCOP - Michigan Cancer Research Consortium, Ann Arbor,  Michigan,  48106,  United States; Recruiting
Minnesota
      CCOP - Duluth, Duluth,  Minnesota,  55805,  United States; Recruiting
      CCOP - Metro-Minnesota, Saint Louis Park,  Minnesota,  55416,  United States; Recruiting
      Coborn Cancer Center, Saint Cloud,  Minnesota,  56303,  United States; Recruiting
      Mayo Clinic Cancer Center, Rochester,  Minnesota,  55905,  United States; Recruiting
      Virginia Piper Cancer Institute at Abbott-Northwestern Hospital, Minneapolis,  Minnesota,  55407,  United States; Recruiting
Montana
      CCOP - Montana Cancer Consortium, Billings,  Montana,  59101,  United States; Recruiting
Nebraska
      CCOP - Missouri Valley Cancer Consortium, Omaha,  Nebraska,  68106,  United States; Recruiting
North Dakota
      Altru Cancer Center, Grand Forks,  North Dakota,  58201,  United States; Recruiting
      CCOP - Merit Care Hospital, Fargo,  North Dakota,  58122,  United States; Recruiting
      Medcenter One Health System, Bismarck,  North Dakota,  58501-5505,  United States; Recruiting
Ohio
      CCOP - Dayton, Dayton,  Ohio,  45429,  United States; Recruiting
      CCOP - Toledo Community Hospital, Toledo,  Ohio,  43623-3456,  United States; Recruiting
Oklahoma
      CCOP - Oklahoma, Tulsa,  Oklahoma,  74136,  United States; Recruiting
Pennsylvania
      Allegheny General Hospital, Pittsburgh,  Pennsylvania,  15212-4772,  United States; Recruiting
      CCOP - Geisinger Clinic and Medical Center, Danville,  Pennsylvania,  17822-2001,  United States; Recruiting
South Carolina
      CCOP - Upstate Carolina, Spartanburg,  South Carolina,  29303,  United States; Recruiting
South Dakota
      CCOP - Sioux Community Cancer Consortium, Sioux Falls,  South Dakota,  57104,  United States; Recruiting
      Rapid City Regional Hospital, Rapid City,  South Dakota,  57709,  United States; Recruiting
Wisconsin
      CCOP - St. Vincent Hospital Cancer Center, Green Bay, Green Bay,  Wisconsin,  54301,  United States; Recruiting
Canada, Saskatchewan
      Allan Blair Cancer Centre at Pasqua Hospital, Regina,  Saskatchewan,  S4T 7T1,  Canada; Recruiting

Study chairs or principal investigators

Edith A. Perez, MD,  Study Chair,  Mayo Clinic - Jacksonville   
Roscoe F. Morton, MD, FACP,  John Stoddard Cancer Center at Iowa Methodist Medical Center   

Study ID Numbers:  CDR0000393224; NCCTG-N0336; NCT00096434
Record last reviewed:  October 2004
Last Updated:  April 4, 2005
Record first received:  November 9, 2004
ClinicalTrials.gov Identifier:  NCT00096434
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08