Clinical trial NCT00095706: Treatment of HER2-Positive Metastatic Breast Cancer With Herceptin and Bevacizumab (Antibodies Against HER2 and VEGF)
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Breast Cancer
Keywords: Metastatic breast cancer
HER2
Trastuzumab
Herceptin
VEGF
Bevacizumab
Avastin
Lead sponsor: Translational Oncology Research International
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
First posted: 2004-11-08
Enrollment: 50
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility 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)

Primary outcomes:
measure: 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:
measure: To evaluate the clinical safety and toxicities of rhuMAb VEGF when administered in combination with Herceptin
measure: To characterize the pharmacokinetics of rhuMAb VEGF and Herceptin given in combination
measure: 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
Other outcomes:
Locations:
city: Alhambra
country: United States
facility: Central Hematology Oncology Medical Group, Inc.
state: California
city: Bakersfield
country: United States
facility: Comprehensive Blood and Cancer Center
state: California
city: Fullerton
country: United States
facility: Virginia K. Crosson Cancer Center
state: California
city: Long Beach
country: United States
facility: Pacific Shores Medical Group
state: California
city: Los Angeles
country: United States
facility: UCLA Medical Center
state: California
city: Northridge
country: United States
facility: North Valley Hematology/Oncology Medical Group
state: California
city: Oxnard
country: United States
facility: Ventura County Hematology-Oncology Specialists
state: California
city: Pomona
country: United States
facility: Wilshire Oncology Medical Group, Inc.
state: California
city: Redondo Beach
country: United States
facility: Cancer Care Associates Medical Group, Inc.
state: California
city: Santa Barbara
country: United States
facility: Sansum Santa Barbara Medical Foundation Clinic
state: California
city: Santa Barbara
country: United States
facility: Santa Barbara Hematology Oncology Medical Group, Inc.
state: California
city: Vista
country: United States
facility: San Diego Cancer Center
state: California
city: Orlando
country: United States
facility: Cancer Institute of Florida, P.A.
state: Florida
city: Athens
country: United States
facility: Northeast Georgia Cancer Care, LLC
state: Georgia
city: Lawrenceville
country: United States
facility: Suburban Hematology-Oncology Associates, P.A.
state: Georgia
city: Marietta
country: United States
facility: Northwest Georgia Oncology Centers, P.C.
state: Georgia
city: Peoria
country: United States
facility: Oncology Hematology Associates of Central Illinois, P.C.
state: Illinois
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
Study officials:
affiliation: University of California, Los Angeles
name: Mark D Pegram, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Chief Medical Officer, TORI
name: Fairooz Kabbinavar, MD
role: STUDY_CHAIR
References: