Bevacizumab and Docetaxel in Treating Women With Locally Advanced or Metastatic Breast Cancer

Stage IV Breast Cancer Clinical Trial

Official title:

PHASE 2 STUDY OF BEVACIZUMAB IN COMBINATION WITH DOCETAXEL IN PATIENTS WITH ADVANCED BREAST CANCER

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00055861
• Other study ID #: NCI-2012-01433
• Secondary ID: OSU 0218NCI-2715
• Status: Completed
• Phase: Phase 2
• First received: March 6, 2003
• Last updated: June 3, 2013
• Start date: July 2002

Study information

• Verified date: June 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This phase II trial is to see if combining bevacizumab with docetaxel works in treating women who have locally advanced or metastatic breast cancer. Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies, such as bevacizumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or deliver cancer-killing substances to them. Combining chemotherapy with monoclonal antibody therapy may kill more tumor cells.

Description:

PRIMARY OBJECTIVES:

I. Determine the response rate in women with locally advanced or metastatic breast cancer treated with bevacizumab and docetaxel.

II. Determine the side effects of this regimen in these patients. III. Correlate soluble activated endothelial cell markers and adhesion molecules, quantitation of tumor and/or endothelial cell apoptosis, and quantitation of microvessel density with clinical outcome in patients treated with this regimen.

OUTLINE: This is a multicenter study. Patients receive bevacizumab IV over 30-90 minutes on weeks 1 and 3 and docetaxel IV over 60 minutes on weeks 1, 2, and 3. Treatment repeats every 4 weeks for up to 12 courses in the absence of unacceptable toxicity or disease progression. After completion of 6 courses of combined treatment, patients with an ongoing response may receive bevacizumab alone in the absence of disease progression.

PROJECTED ACCRUAL: A total of 16-27 patients will be accrued for this study within 14-27 months.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. primary completion date: August 2006
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically or cytologically confirmed breast cancer

• Local-regional recurrences or metastatic disease

• At least 1 unidimensionally measurable lesion at least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan

• No history or evidence of CNS disease (e.g., primary brain tumor or any brain metastases)

• Hormone receptor status:

• Not specified

• Female

• Performance status - ECOG 0-2

• Performance status - Karnofsky 60-100%

• More than 3 months

• WBC at least 3,000/mm^3

• Absolute neutrophil count at least 1,500/mm^3

• Platelet count at least 100,000/mm^3

• No bleeding diathesis or coagulopathy

• Bilirubin normal

• AST/ALT no greater than 2.5 times upper limit of normal

• INR less than 1.5 (patients receiving warfarin)

• Creatinine normal

• Creatinine clearance at least 60 mL/min

• No baseline proteinuria

• Patients with proteinuria of 1+ or greater at baseline are allowed provided 24-hour urinary protein is less than 500 mg

• No symptomatic congestive heart failure

• No cardiac arrhythmia

• No uncontrolled hypertension

• No history of stroke

• No clinically significant peripheral artery disease

• No arterial thromboembolic event within the past 6 months, including any of the following:

• Transient ischemic attack

• Cerebrovascular accident

• Unstable angina

• Myocardial infarction

• HIV negative

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No seizures not controlled with standard medical therapy

• No prior allergic reactions attributed to compounds of similar chemical or biological composition to study agents

• No psychiatric illness or social situation that would preclude study compliance

• No ongoing or active infection

• No other concurrent uncontrolled illness

• No non-healing wounds

• No significant traumatic injury within the past 28 days

• Prior adjuvant chemotherapy allowed (up to 1 regimen for metastatic disease)

• More than 6 months since prior taxane-containing adjuvant chemotherapy

• More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered

• More than 3 weeks since prior radiotherapy

• More than 28 days since prior major surgery or open biopsy

• More than 7 days since prior fine needle aspirations other than in the breast

• More than 7 days since prior placement of a vascular access device

• No concurrent major surgical procedure

• No concurrent or recent full-dose oral or parenteral anticoagulants or thrombolytic agents (except as required to maintain patency of preexisting, permanent indwelling IV catheters)

• No other concurrent investigational agents

• No concurrent chronic daily aspirin (more than 325 mg/day) or nonsteroidal anti-inflammatory medications (known to inhibit platelet function at doses used to treat chronic inflammatory diseases)

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Neoplasms
• Recurrent Breast Cancer
• Stage IV Breast Cancer

Intervention

Biological:
• bevacizumab
Given IV

Drug:
• docetaxel
Given IV

Other:
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
United States	University of Colorado Cancer Center - Anschutz Cancer Pavilion	Aurora	Colorado
United States	Ohio State University Medical Center	Columbus	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response rate according to Response Evaluation Criteria in Solid Tumors (RECIST)	The response rate will be estimated with exact binomial 95% confidence intervals.	Up to 4 years	No
Primary	Side effects as assessed by the National Cancer Institute (NCI) Common Toxicity Criteria (CTC) version 2.0		Up to 4 years	No
Secondary	Correlation of biologic studies with clinical outcomes	Associations between laboratory endpoints (pre-study plasma VEGF and IL-8, E-selectin, P-selectin, CD31, ICAM-1, VCAM_1, CD44, PDGF, FGF, MMP-2 and MMP-9.) and response or toxicity will be investigated using Wilcoxon rank-sum tests for ordinal or continuous endpoints, or chi-square tests for binary or categorical endpoints.	Up to 4 years	No