Phase II Bevacizumab + Tax In Advanced Breast Cancer

NCT ID: NCT00027885

Last Updated: 2013-06-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 49 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2001-11-30
• Study Completion Date: 2010-08-31

Brief Summary

RATIONALE: 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.

PURPOSE: This randomized phase II trial is to see if docetaxel with or without bevacizumab followed by surgery, radiation therapy, and combination chemotherapy works better in treating patients who have stage III or stage IV breast cancer.

Detailed Description

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.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Docetaxel

Patients receive docetaxel IV over 1 hour once weekly on weeks 1-6.

Group Type: ACTIVE_COMPARATOR

cyclophosphamide

Intervention Type: DRUG

Approximately 4 weeks after the completion of radiotherapy, patients receive 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.

docetaxel

Intervention Type: DRUG

Patients receive docetaxel IV over 1 hour once weekly on weeks 1-6.

doxorubicin hydrochloride

Intervention Type: DRUG

Approximately 4 weeks after the completion of radiotherapy, patients receive doxorubicin IV over 5 minutes. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

adjuvant therapy

Intervention Type: PROCEDURE

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.

conventional surgery

Intervention Type: PROCEDURE

After the second course, patients with stable or responsive disease undergo modified radical mastectomy or breast-conserving surgery.

neoadjuvant therapy

Intervention Type: PROCEDURE

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.

radiation therapy

Intervention Type: RADIATION

Three to six weeks after surgery, patients undergo radiotherapy 5 days a week for 7 weeks.

Combine bevacizumab and docetaxel.

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.

Group Type: EXPERIMENTAL

bevacizumab

Intervention Type: BIOLOGICAL

Patients receive bevacizumab IV over 60 minutes once every 2 weeks on weeks 1-8.

cyclophosphamide

Intervention Type: DRUG

Approximately 4 weeks after the completion of radiotherapy, patients receive 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.

doxorubicin hydrochloride

Intervention Type: DRUG

Approximately 4 weeks after the completion of radiotherapy, patients receive doxorubicin IV over 5 minutes. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

adjuvant therapy

Intervention Type: PROCEDURE

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.

conventional surgery

Intervention Type: PROCEDURE

After the second course, patients with stable or responsive disease undergo modified radical mastectomy or breast-conserving surgery.

neoadjuvant therapy

Intervention Type: PROCEDURE

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.

radiation therapy

Intervention Type: RADIATION

Three to six weeks after surgery, patients undergo radiotherapy 5 days a week for 7 weeks.

Interventions

bevacizumab

Patients receive bevacizumab IV over 60 minutes once every 2 weeks on weeks 1-8.

Intervention Type: BIOLOGICAL

cyclophosphamide

Approximately 4 weeks after the completion of radiotherapy, patients receive 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.

Intervention Type: DRUG

docetaxel

Patients receive docetaxel IV over 1 hour once weekly on weeks 1-6.

Intervention Type: DRUG

doxorubicin hydrochloride

Approximately 4 weeks after the completion of radiotherapy, patients receive doxorubicin IV over 5 minutes. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

Intervention Type: DRUG

adjuvant therapy

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.

Intervention Type: PROCEDURE

conventional surgery

After the second course, patients with stable or responsive disease undergo modified radical mastectomy or breast-conserving surgery.

Intervention Type: PROCEDURE

neoadjuvant therapy

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.

Intervention Type: PROCEDURE

radiation therapy

Three to six weeks after surgery, patients undergo radiotherapy 5 days a week for 7 weeks.

Intervention Type: RADIATION

Other Intervention Names

Taxotere

Eligibility Criteria

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

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

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Case Comprehensive Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Paula Silverman, MD

Role: STUDY_CHAIR

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

Locations

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

Cleveland, Ohio, United States

UH-Southwest

Middleburg Heights, Ohio, United States

UH-Chagrin Highlands

Orange, Ohio, United States

UH-Green Road

South Euclid, Ohio, United States

UH-Westlake

Westlake, Ohio, United States

Countries

United States

Other Identifiers

U01CA062502

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA043703

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CWRU-3100

Identifier Type: OTHER

Identifier Source: secondary_id

NCI-2722

Identifier Type: OTHER

Identifier Source: secondary_id

CWRU3100

Identifier Type: -

Identifier Source: org_study_id