The purpose of this study is to evaluate the safety and effectiveness of combined treatment with trastuzumab (Herceptin) and bevacizumab (anti-VEGF antibody) in patients with HER2-positive metastatic breast cancer.

Condition	Treatment or Intervention	Phase
Breast Cancer	Drug: Bevacizumab (drug), Herceptin (drug)	Phase I Phase II

Further Study Details: 

Primary Outcomes: To establish the maximum tolerated dose (MTD) or recommended phase II dose of rhuMAb VEGF (bevacizumab) administered intravenously every 14 days to patients with HER2-amplified relapsed or metastatic breast cancer receiving concomitant Herceptin therapy
Secondary Outcomes: To evaluate the clinical safety and toxicities of rhuMAb VEGF when administered in combination with Herceptin; To characterize the pharmacokinetics of rhuMAb VEGF and Herceptin given in combination; To evaluate the efficacy of rhuMAb VEGF plus Herceptin in terms of clinical activity when administered as an intravenous infusion, in patients with previously untreated metastatic or relapsed breast cancer
Expected Total Enrollment:  50

Based on preclinical experiments conducted in our laboratories, we hypothesize that the aggressive behavior of HER2-overexpressing breast cancers is due in part to increased angiogenesis resulting from HER2-induced increases in vascular endothelial growth factor (VEGF) expression. In vivo experiments suggest that combined blockade of the HER2 receptor and VEGF results in superior anti-tumor efficacy compared with either treatment alone.

The current clinical trial, for which the phase I portion has been completed, will examine the efficacy and safety of trastuzumab (Herceptin) and bevacizumab (anti-VEGF antibody) in the treatment of HER2-overexpressing metastatic breast cancer.

Ages Eligible for Study:  18 Years   -   75 Years,  Genders Eligible for Study:  Female

Criteria

Inclusion Criteria:

• Metastatic or relapsed locally advanced breast cancer
• HER2-positive by FISH
• No prior chemotherapy for metastatic disease
• ECOG performance status 0-2
• Normal left ventricular ejection fraction
• Bidimensionally measurable disease
• Oxygen saturation > 90% on room air

Exclusion Criteria:

• Other invasive malignancy within 5 years
• More than 3 different metastatic sites
• >50% liver involvement by metastasis
• Newly diagnosed untreated Stage IIIB breast cancer
• Prior chemotherapy for metastatic disease
• Clinically significant cardiovascular disease
• History or evidence of CNS disease
• Major surgery within 28 days prior to day 0
• Current or recent use of parenteral anticoagulants
• WBC < 3,000/uL
• Platelet count < 75,000/uL
• Hemoglobin < 9.0 g/dL
• Total Bilirubin > 2.0 mg/dL
• AST or ALT > 5 time upper limit of normal for subjects with documented liver metastases; > 2.5 times upper limit of normal for subjects without evidence of liver metastases
• Proteinuria (> 1g protein/24 hours at baseline)
• Prior therapy with Herceptin or rhuMAb VEGF (bevacizumab)

David M Reese, MD      310-824-1919    dreese@transonc.org
Nancy Ryba, RN      310-794-6500    nryba@mednet.ucla.edu

California
      UCLA Medical Center, Los Angeles,  California,  90095,  United States; Recruiting
      Comprehensive Blood and Cancer Center, Bakersfield,  California,  93309,  United States; Recruiting
      California Oncology of the Central Valley, Fresno,  California,  93710,  United States; Recruiting
      Virginia K. Crosson Cancer Center, Fullerton,  California,  92835,  United States; Recruiting
      Wilshire Oncology Medical Group, Pomona,  California,  91767,  United States; Recruiting
      Pacific Shores Medical Group, Long Beach,  California,  90813,  United States; Recruiting
      Central Hematology Oncology Medical Group, Inc., Monterey Park,  California,  91754,  United States; Recruiting
      North Valley Hematology/Oncology Medical Group, Northridge,  California,  91328,  United States; Recruiting
      Ventura County Hematology-Oncology Specialists, Oxnard,  California,  93030,  United States; Recruiting
      Cancer Care Associates Medical Group, Inc., Redondo Beach,  California,  90277,  United States; Recruiting
      Santa Barbara Hematology Oncology Medical Group, Santa Barbara,  California,  93105,  United States; Recruiting
      Sansum Santa Barbara Medical Foundation Clinic, Santa Barbara,  California,  93105,  United States; Recruiting
      San Diego Cancer Center Medical Group, Vista,  California,  92081,  United States; Recruiting
Florida
      Hematology and Oncology Associates, P.A., Orlando,  Florida,  32804,  United States; Recruiting
Georgia
      Hematology & Oncology of Northeast Georgia, Athens,  Georgia,  30607,  United States; Recruiting
      Peachtree Hematology & Oncology Consultants, P.C., Atlanta,  Georgia,  30309,  United States; Recruiting
      Medical Oncology Associates, P.C., Augusta,  Georgia,  30901,  United States; Recruiting
      Central Georgia Hematology/Oncology Associates, P.C., Macon,  Georgia,  31201,  United States; Recruiting
      Northwest Georgia Oncology Centers, P.C., Marietta,  Georgia,  30060,  United States; Recruiting
      Atlanta Cancer Care, Roswell,  Georgia,  30076,  United States; Recruiting
      Suburban Hematology-Oncology Associates, Snellville,  Georgia,  30078,  United States; Recruiting
Illinois
      Oncology Hematology Associates of Central Illinois, P.C., Peoria,  Illinois,  61615,  United States; Recruiting
Nevada
      Comprehensive Cancer Centers of Nevada, Las Vegas,  Nevada,  89109,  United States; Recruiting

Study chairs or principal investigators

Mark D Pegram, MD,  Study Chair,  University of California, Los Angeles   
David M Reese, MD,  Study Director,  Translational Oncology Research International (TORI)   

Study ID Numbers:  TORI B-03; Western IRB #20041069; UCLA IRB #01-09-030
Record last reviewed:  January 2005
Last Updated:  January 18, 2005
Record first received:  November 5, 2004
ClinicalTrials.gov Identifier:  NCT00095706
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-04-08