Treatment of HER2-Positive Metastatic Breast Cancer With Herceptin and Bevacizumab (Antibodies Against HER2 and VEGF)

Sponsor

Translational Oncology Research International (Other)

Overall Status

Completed

CT.gov ID

NCT00095706

Collaborator

Genentech, Inc. (Industry)

Enrollment

Locations

103

Duration (Months)

2.8

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: Bevacizumab (drug), Herceptin (drug)	Phase 1/Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase I/II Combined Biological Therapy of Breast Cancer Using Monoclonal Antibodies Directed Against HER2/Neu Proto-Oncogene and Vascular Endothelial Growth Factor

Study Start Date :

Jun 1, 2003

Actual Primary Completion Date :

Apr 1, 2007

Actual Study Completion Date :

Jan 1, 2012

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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 []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Central Hematology Oncology Medical Group, Inc.	Alhambra	California	United States	91801
2	Comprehensive Blood and Cancer Center	Bakersfield	California	United States	93309
3	Virginia K. Crosson Cancer Center	Fullerton	California	United States	92835
4	Pacific Shores Medical Group	Long Beach	California	United States	90813
5	UCLA Medical Center	Los Angeles	California	United States	90095
6	North Valley Hematology/Oncology Medical Group	Northridge	California	United States	91328
7	Ventura County Hematology-Oncology Specialists	Oxnard	California	United States	93030
8	Wilshire Oncology Medical Group, Inc.	Pomona	California	United States	91767
9	Cancer Care Associates Medical Group, Inc.	Redondo Beach	California	United States	90277
10	Sansum Santa Barbara Medical Foundation Clinic	Santa Barbara	California	United States	93105
11	Santa Barbara Hematology Oncology Medical Group, Inc.	Santa Barbara	California	United States	93105
12	San Diego Cancer Center	Vista	California	United States	92081
13	Cancer Institute of Florida, P.A.	Orlando	Florida	United States	32804
14	Northeast Georgia Cancer Care, LLC	Athens	Georgia	United States	30607
15	Suburban Hematology-Oncology Associates, P.A.	Lawrenceville	Georgia	United States	30045
16	Northwest Georgia Oncology Centers, P.C.	Marietta	Georgia	United States	30060
17	Oncology Hematology Associates of Central Illinois, P.C.	Peoria	Illinois	United States	61615
18	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada	United States	89109