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

Phase 2

Completed

• Conditions: Breast Cancer
• Interventions: Drug: Trastuzumab; Drug: Bevacizumab; Drug: Docetaxel

• Registration Number: NCT00428922
• Lead Sponsor: Bhuvaneswari Ramaswamy

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.

Study Timeline

• Study First Submitted: 2007-01-29
• Study First Submitted QC: 2007-01-29
• Study First Posted: 2007-01-30
• Study Start: 2007-06-14
• Primary Completion: 2012-11-01
• Results First Submitted: 2015-11-10
• Results First Submitted QC: 2016-01-14
• Results First Posted: 2016-02-12
• Study Completion: 2017-02-07
• Status Verified: 2018-07
• Last Update Submitted: 2018-07-11
• Last Update Posted: 2018-08-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 26

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Progression-free Survival (PFS) and to Evaluate Safety of the Trastuzumab, Bevacizumab and Docetaxel Regimen.	up to 3 years	The trial was designed as a single-stage phase II rather then usual two-stage design because of the progression free survival (PFS) primary endpoint, as it is impractical to wait to assess PFS for patients in the first stage. We will consider a PFS of 50% at twelve months (median PFS of 12 months) or less uninteresting and a PFS of 70% at twelve months (median PFS of twenty months) worthy of pursuing the regimen in a future trials. The single-stage design is as follows: p0=0.50, p1=0.70, α=0.10, β= 0.10. This leads to a total sample size of 39 patients, 24 or higher of who are progression-free at 12 months.

Secondary Outcome Measures

Name	Time	Method
Changes in CTCs as Predictors of PFS and Clinical Benefit	Day 1 and Day 22	Circulating tumor cells (CTCs) evaluated at baseline (day 1 of treatment) and after 1 treatment cycle (day 22 prior to cycle 2 treatment).
Overall Clinical Benefit Rate (CR+PR+SD)	at least 24 weeks	Defined as best response of CR or PR or stable disease for at least 24 weeks. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI and/or CT: Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for a Partial Response nor sufficient increase to qualify for Progression of Disease (POD); POD, 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Complete Response (CR), Disappearance of all target lesions
Changes in CECs as Predictors of PFS and Clinical Benefit	Day 1 and Day 22	Circulating endothelial cells (CECs) are to be collected day 1 prior to treatment and day 22 prior to treatment. These samples are to be collected at the PI's discretion based upon the availability of the cell processing laboratory, the patients will be informed when consented if the samples will collected or not.

Trial Locations

Locations (3)

Cleveland Clinic Foundation; 🇺🇸 Cleveland, Ohio, United States

Ohio State University; 🇺🇸 Columbus, Ohio, United States

University of Pittsburgh; 🇺🇸 Pittsburgh, Pennsylvania, United States