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A Randomized Phase II Study of Bevacizumab in Combination With Docetaxel in Locally Advanced Breast Cancer


Phase 2
18 Years
N/A
Not Enrolling
Both
Breast Cancer

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Trial Information

A Randomized Phase II Study of Bevacizumab in Combination With Docetaxel in Locally Advanced Breast Cancer


OBJECTIVES:

- Determine the effect of bevacizumab and docetaxel on reduction of microvessel density
and induction of apoptosis of endothelial and tumor cells in patients with locally
advanced breast cancer.

- Determine the safety profile of this regimen in these patients.

- Compare the effect of docetaxel and bevacizumab, in terms of objective response,
stabilization of disease, and progression-free survival, in these patients.

OUTLINE: This is a randomized study. Patients are stratified according to disease stage.
Patients are randomized to 1 of 2 treatment arms.

- Arm I: Patients receive docetaxel IV over 1 hour once weekly on weeks 1-6 and
bevacizumab IV over 60 minutes once every 2 weeks on weeks 1-8.

- Arm II: Patients receive docetaxel as in arm I. Treatment in both arms repeats every 8
weeks for 2 courses in the absence of disease progression or unacceptable toxicity.

After the second course, patients with stable or responsive disease undergo modified radical
mastectomy or breast-conserving surgery. Three to six weeks after surgery, patients undergo
radiotherapy 5 days a week for 7 weeks.

Approximately 4 weeks after the completion of radiotherapy, patients receive doxorubicin IV
over 5 minutes and cyclophosphamide IV over 30-60 minutes on day 1. Treatment repeats every
21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

Patients with estrogen and/or progesterone receptor-positive disease also receive oral
tamoxifen daily for 5 years beginning after the completion of chemotherapy. Post-menopausal
patients may receive oral anastrozole once daily for 5 years instead of tamoxifen.

Patients are followed at 3, 6, and 12 months, every 6 months for 4 years, and then annually
thereafter.

PROJECTED ACCRUAL: A total of 60 patients (30 per treatment arm) will be accrued for this
study.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically confirmed adenocarcinoma of the breast

- Stage IIIA or IIIB

- Stage IV if patient has clinical evidence of locally advanced breast cancer only

- Inoperable disease

- Prior carcinoma in situ of the breast or bilateral breast cancer is allowed

- No CNS metastases

- Hormone receptor status:

- Estrogen and progesterone receptor status known

PATIENT CHARACTERISTICS:

Age:

- 18 and over

Sex:

- Female or male

Menopausal status:

- Not specified

Performance status:

- ECOG 0-2 OR

- Karnofsky 60-100%

Life expectancy:

- More than 6 months

Hematopoietic:

- WBC at least 3,000/mm^3

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

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

Hepatic:

- Bilirubin normal (no greater than 2 times upper limit of normal [ULN] in patients
with an inherited disorder)

- AST/ALT no greater than 2.5 times ULN

- INR and PTT normal

Renal:

- Creatinine normal OR

- Creatinine clearance at least 60 mL/min

- No proteinuria or clinically significant renal impairment

Cardiovascular:

- LVEF at least 45% by echocardiogram or MUGA scan

- No New York Heart Association class III or IV heart disease

- No symptomatic congestive heart failure

- No unstable angina pectoris

- No cardiac arrhythmia

- No inadequately controlled hypertension

- No history of deep vein thrombosis or other thromboses

- No clinically significant peripheral artery disease

- No arterial thromboembolic event within the past 6 months including the following:

- Transient ischemic attack

- Cerebrovascular accident

- Myocardial infarction

Other:

- No other prior or concurrent malignancy within the past 10 years except inactive
nonmelanoma skin cancer or carcinoma in situ of the cervix

- No other uncontrolled concurrent illness

- No ongoing or active infection

- No non-healing wounds

- No psychiatric illness or social situation that would preclude study participation

- No prior allergic reaction to compounds of similar chemical or biological composition
to bevacizumab, docetaxel, polysorbate 80 (Tween) formulations, or other agents used
in this study

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective barrier contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- No concurrent cytokines during docetaxel/bevacizumab administration

- Concurrent cytokines during doxorubicin/cyclophosphamide administration allowed
at the discretion of the treating physician

Chemotherapy:

- No prior chemotherapy

Endocrine therapy:

- Prior hormonal therapy (e.g., tamoxifen) allowed

Radiotherapy:

- Prior radiotherapy to affected breast allowed

Surgery:

- More than 28 days since prior major surgery

Other:

- At least 10 days since prior thrombolytic agents

- At least 10 days since prior full-dose oral or parenteral anticoagulants except to
maintain patency of permanent indwelling IV catheters

- Concurrent warfarin allowed provided INR is less than 1.5

- Concurrent bisphosphonates allowed for osseous metastases provided they are not
initiated on day 1 of cycle 1

- No concurrent combination antiretroviral therapy for HIV-positive patients

- No concurrent full-dose oral or parenteral anticoagulants except to maintain patency
of permanent indwelling IV catheters

- No concurrent thrombolytic agents

- No other concurrent anticancer agents or therapies

- No other concurrent investigational agents

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To evaluate the ability of bevacizumab and docetaxel to reduce microvessel density and induce apoptosis of endothelial and tumor cells.

Outcome Description:

The primary outcome measure is the difference in change in biologic parameters between the two arms. Tumor biopsies are required to perform pre- and post-treatment tumor microvessel density determination, apoptosis by TUNEL assay, proliferation markers by immunohistochemistry(e.g. PCNA, Ki-67), and expression of nuclear clusterin/XIP8.

Outcome Time Frame:

weeks 8 and 17

Safety Issue:

No

Principal Investigator

Paula Silverman, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

Authority:

United States: Federal Government

Study ID:

CWRU3100

NCT ID:

NCT00027885

Start Date:

November 2001

Completion Date:

August 2010

Related Keywords:

  • Breast Cancer
  • stage IV breast cancer
  • stage IIIA breast cancer
  • stage IIIB breast cancer
  • stage IIIC breast cancer
  • male breast cancer
  • Breast Neoplasms

Name

Location

Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer CenterCleveland, Ohio  44106-5065
UH-SouthwestMiddleburgh Heights, Ohio  44130
UH-Chagrin HighlandsOrange Village, Ohio  44122
UH-Green RoadSouth Euclid, Ohio  44121
UH-WestlakeWestlake, Ohio  44145