Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Docetaxel With or Without Bevacizumab Followed by Surgery, Radiation Therapy, and Combination Chemotherapy in Treating Patients With Locally Advanced Breast Cancer(Closed to accrual as of 11/05/09)

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Closed	18 and over	NCI	CWRU-3100 NCI-2722, NCT00027885, 2722, CASE-3100

Objectives

1. 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.
2. Determine the safety profile of this regimen in these patients.
3. Compare the effect of docetaxel and bevacizumab, in terms of objective response, stabilization of disease, and progression-free survival, in these patients.

Entry 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

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

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/mm³
• Absolute neutrophil count at least 1,500/mm³
• Platelet count at least 100,000/mm³

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

Expected Enrollment

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

Outcomes

Tumor microvessel density and apoptosis as measured by breast biopsy at baseline, and weeks 8 and 17
Tumor perfusion as measured by MRI at baseline, and weeks 8 and 17

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.

Trial Contact Information

Trial Lead Organizations

Ireland Cancer Center at University Hospitals/Case Medical Center

Paula Silverman, MD, Protocol chair		Ph: 216-844-8510 Email: pxs7@case.edu

Registry Information
Official Title		A Randomized Phase II Study of Bevacizumab in Combination with Docetaxel in Locally Advanced Breast Cancer
Trial Start Date		2001-11-16
Registered in ClinicalTrials.gov		NCT00027885
Date Submitted to PDQ		2001-10-18
Information Last Verified		2005-09-07
NCI Grant/Contract Number		CA43703, CA62502

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