Clinical trial NCT00428922: Trastuzumab (Herceptin), Bevacizumab, and Docetaxel (Taxotere) Trial in Stage IV Metastatic Breast Cancer (MBC) Patients
Official title: Phase II Trial of Trastuzumab (Herceptin), Bevacizumab, and Docetaxel (Taxotere) Trial in Stage IV Metastatic Breast Cancer (MBC) Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: Metastatic
Breast Cancer
MBC
Lead sponsor: Ohio State University Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
name: Case Comprehensive Cancer Center
name: University of Pittsburgh
First posted: 2007-01-30
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary objectives are to determine the progression-free survival (PFS) and to evaluate safety of the trastuzumab, bevacizumab and docetaxel regimen.

Detailed description: Rationale: Antibodies are proteins that are normally part of the immune system that bind to foreign agents in the body. Researchers manufacture antibodies outside of the human body that bind to specific targets such as proteins in cancer cells. Herceptin is a monoclonal antibody that binds to the human epidermal growth factor receptor (HER-2), and can kill HER2-positive cancer cells. Herceptin is used to treat breast cancer that is HER2-positive, and has spread after treatment with other drugs. Bevacizumab is a signal transduction inhibitor that works by preventing the growth of new blood vessels from surrounding tissue into tumors. Bevacizumab specifically inhibits the vascular endothelial growth factor (VEGF), a substance made by cells that stimulates new blood vessel formation. Research indicates that HER-2 signaling helps to induce VEGF expression. Therefore, cancer treatments targeting both HER-2 and VEGF may improve anti-cancer efficacy in patients. Docetaxel is a chemotherapy agent used against breast and other types of cancer. The current study builds on previous research suggesting the safety and potential for efficacy with combination trastuzumab, bevacizumab, and docetaxel.

Purpose: The primary objectives are to determine the progression free survival and evaluate the safety of trastuzumab, bevacizumab, and docetaxel. Secondary objectives are to assess early changes in circulating tumor cells and circulating endothelial cells as predictors of progression free survival and clinical benefit, as well as to determine the overall clinical benefit rate.

Treatment: Study participants will be given trastuzumab, bevacizumab, and docetaxel. All study drugs will be given through intravenous infusions once every 21 days. A cycle is considered 3 weeks. A minimum of 6 study treatment cycles is required unless study participants experience disease growth or intolerable toxicity. The decision to stop docetaxel after 6 cycles is up to the discretion of the treating physician and the patient. Study participants who are deriving a benefit from the study drugs may continue on trastuzumab and bevacizumab alone. Several tests and exams will be given throughout the study to closely monitor study participants.

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed breast cancer with evidence of metastatic disease
* HER2 3+ or FISH (fluorescent in situ hybridization)+
* Age ≥ 18 years
* No prior trastuzumab, except as given in the adjuvant or neoadjuvant setting.
* No prior chemotherapy in the metastatic setting.

Exclusion Criteria:

* CNS (central nervous system) metastases
* Prior radiation therapy within the last 4 weeks
* Pregnant (positive pregnancy test) or lactating women
* Major surgical procedure, open biopsy, non-healing wounds, or significant traumatic injury within 28 days prior to starting study or anticipation of need for major surgical procedure during the study
* Minor surgical procedures such as fine needle aspirations or core biopsies within 7 days prior to start of study.

Primary outcomes:
measure: Progression-free Survival (PFS) and to Evaluate Safety of the Trastuzumab, Bevacizumab and Docetaxel Regimen.
timeFrame: up to 3 years
Secondary outcomes:
measure: Changes in CTCs as Predictors of PFS and Clinical Benefit
timeFrame: Day 1 and Day 22
measure: Overall Clinical Benefit Rate (CR+PR+SD)
timeFrame: at least 24 weeks
measure: Changes in CECs as Predictors of PFS and Clinical Benefit
timeFrame: Day 1 and Day 22
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
Study officials:
affiliation: Ohio State University
name: Bhuvaneswari Ramaswamy, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Puhalla S, Mrozek E, Young D, Ottman S, McVey A, Kendra K, Merriman NJ, Knapp M, Patel T, Thompson ME, Maher JF, Moore TD, Shapiro CL. Randomized phase II adjuvant trial of dose-dense docetaxel before or after doxorubicin plus cyclophosphamide in axillary node-positive breast cancer. J Clin Oncol. 2008 Apr 1;26(10):1691-7. doi: 10.1200/JCO.2007.14.3941. Epub 2008 Mar 3.