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

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00095706
• Other study ID #: TORI B-03
• Secondary ID: Western IRB #200
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: November 5, 2004
• Last updated: September 23, 2015
• Start date: June 2003
• Est. completion date: January 2012

Study information

• Verified date: September 2015
• Source: Translational Oncology Research International
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT00093535

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: January 2012
• Est. primary completion date: April 2007
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 75 Years

Eligibility

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)

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Bevacizumab (drug), Herceptin (drug)

Locations

Country	Name	City	State
United States	Central Hematology Oncology Medical Group, Inc.	Alhambra	California
United States	Northeast Georgia Cancer Care, LLC	Athens	Georgia
United States	Comprehensive Blood and Cancer Center	Bakersfield	California
United States	Virginia K. Crosson Cancer Center	Fullerton	California
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Suburban Hematology-Oncology Associates, P.A.	Lawrenceville	Georgia
United States	Pacific Shores Medical Group	Long Beach	California
United States	UCLA Medical Center	Los Angeles	California
United States	Northwest Georgia Oncology Centers, P.C.	Marietta	Georgia
United States	North Valley Hematology/Oncology Medical Group	Northridge	California
United States	Cancer Institute of Florida, P.A.	Orlando	Florida
United States	Ventura County Hematology-Oncology Specialists	Oxnard	California
United States	Oncology Hematology Associates of Central Illinois, P.C.	Peoria	Illinois
United States	Wilshire Oncology Medical Group, Inc.	Pomona	California
United States	Cancer Care Associates Medical Group, Inc.	Redondo Beach	California
United States	Sansum Santa Barbara Medical Foundation Clinic	Santa Barbara	California
United States	Santa Barbara Hematology Oncology Medical Group, Inc.	Santa Barbara	California
United States	San Diego Cancer Center	Vista	California

Sponsors (2)

Lead Sponsor	Collaborator
Translational Oncology Research International	Genentech, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	To evaluate the clinical safety and toxicities of rhuMAb VEGF when administered in combination with Herceptin
Secondary	To characterize the pharmacokinetics of rhuMAb VEGF and Herceptin given in combination
Secondary	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