Trastuzumab (Herceptin), Bevacizumab, and Docetaxel (Taxotere) Trial in Stage IV Metastatic Breast Cancer (MBC) Patients

NCT ID: NCT00428922

Last Updated: 2018-08-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-06-14
• Study Completion Date: 2017-02-07

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.

Conditions

Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Trastuzumab, Bevacizumab, and Docetaxel

Trastuzumab \[6mg/kg\], Bevacizumab \[15mg/kg\], and Docetaxel \[75 mg/M²\]

Group Type: EXPERIMENTAL

Trastuzumab

Intervention Type: DRUG

administered every three weeks on day 1, every 21 days. The dose given will be 6 mg/kg. The initial loading dose is 8mg/kg and is administered as a 90-minute infusion. Thereafter, the maintenance dose is 6mg/kg every three weeks administered as a 30 minute infusion (unless the treating physician indicates a longer infusion duration is warranted). Trastuzumab is given prior to bevacizumab. Trastuzumab is to be continued until disease progression or unacceptable toxicity.

Bevacizumab

Intervention Type: DRUG

administered every three weeks on day 1, every 21 days. The dose given will be 15 mg/kg. The initial dose is administered over 90 minutes. If the first infusion is well tolerated, the second dose is given over 60 minutes, and if that is well tolerated, then subsequent doses may be given over 30 minutes. Avastin is given after trastuzumab and prior to docetaxel.

Docetaxel

Intervention Type: DRUG

administered every three weeks on day 1, every 21 days. The dose given will be 75 mg/M². All doses of docetaxel are administered over 60 minutes. Docetaxel is given after trastuzumab and bevacizumab.

Interventions

Trastuzumab

administered every three weeks on day 1, every 21 days. The dose given will be 6 mg/kg. The initial loading dose is 8mg/kg and is administered as a 90-minute infusion. Thereafter, the maintenance dose is 6mg/kg every three weeks administered as a 30 minute infusion (unless the treating physician indicates a longer infusion duration is warranted). Trastuzumab is given prior to bevacizumab. Trastuzumab is to be continued until disease progression or unacceptable toxicity.

Intervention Type: DRUG

Bevacizumab

administered every three weeks on day 1, every 21 days. The dose given will be 15 mg/kg. The initial dose is administered over 90 minutes. If the first infusion is well tolerated, the second dose is given over 60 minutes, and if that is well tolerated, then subsequent doses may be given over 30 minutes. Avastin is given after trastuzumab and prior to docetaxel.

Intervention Type: DRUG

Docetaxel

administered every three weeks on day 1, every 21 days. The dose given will be 75 mg/M². All doses of docetaxel are administered over 60 minutes. Docetaxel is given after trastuzumab and bevacizumab.

Intervention Type: DRUG

Other Intervention Names

Herceptin; Avastin; Taxotere

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genentech, Inc.

INDUSTRY

Sponsor Role: collaborator

Case Comprehensive Cancer Center

OTHER

Sponsor Role: collaborator

University of Pittsburgh

OTHER

Sponsor Role: collaborator

Bhuvaneswari Ramaswamy

OTHER

Sponsor Role: lead

Responsible Party

Bhuvaneswari Ramaswamy

Principal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Bhuvaneswari Ramaswamy, MD

Role: PRINCIPAL_INVESTIGATOR

Ohio State University

Locations

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Ohio State University

Columbus, Ohio, United States

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 18316792 (View on PubMed)

Related Links

http://cancer.osu.edu

Jamesline

Other Identifiers

NCI-2011-03219

Identifier Type: REGISTRY

Identifier Source: secondary_id

OSU-06027

Identifier Type: -

Identifier Source: org_study_id