Phase II Bevacizumab + Tax In Advanced Breast Cancer

NCT00027885 | Completed Phase 2 DMC

• 5 other identifiers: CWRU3100U01CA062502P30CA043703CWRU-3100NCI-2722
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 5

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.

Conditions

Breast Cancer

Keywords

stage IV breast cancer; stage IIIA breast cancer; stage IIIB breast cancer; stage IIIC breast cancer; male breast cancer

Outcome Measures

Primary Outcomes (1)

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

  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.

  weeks 8 and 17

Secondary Outcomes (1)

• Number of patients with objective response

  5 years

Study Arms (2)

Docetaxel

ACTIVE COMPARATOR

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

Drug: cyclophosphamide; Drug: docetaxel; Drug: doxorubicin hydrochloride; Procedure: adjuvant therapy; Procedure: conventional surgery; Procedure: neoadjuvant therapy; Radiation: radiation therapy

Combine bevacizumab and docetaxel.

EXPERIMENTAL

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.

Biological: bevacizumab; Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Procedure: adjuvant therapy; Procedure: conventional surgery; Procedure: neoadjuvant therapy; Radiation: radiation therapy

Interventions

bevacizumab BIOLOGICAL

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

Combine bevacizumab and docetaxel.

cyclophosphamide 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.

Combine bevacizumab and docetaxel.; Docetaxel

docetaxel DRUG

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

Also known as: Taxotere

Docetaxel

doxorubicin hydrochloride 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.

Combine bevacizumab and docetaxel.; Docetaxel

adjuvant therapy 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.

Combine bevacizumab and docetaxel.; Docetaxel

conventional surgery PROCEDURE

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

Combine bevacizumab and docetaxel.; Docetaxel

neoadjuvant therapy 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.

Combine bevacizumab and docetaxel.; Docetaxel

radiation therapy RADIATION

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

Combine bevacizumab and docetaxel.; Docetaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Case Comprehensive Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (5)

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

Cleveland, Ohio, 44106-5055, United States

Location

UH-Southwest

Middleburg Heights, Ohio, 44130, United States

Location

UH-Chagrin Highlands

Orange, Ohio, 44122, United States

Location

UH-Green Road

South Euclid, Ohio, 44121, United States

Location

UH-Westlake

Westlake, Ohio, 44145, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Breast Neoplasms, Male

Interventions

Bevacizumab; Cyclophosphamide; Docetaxel; Doxorubicin; Chemotherapy, Adjuvant; Neoadjuvant Therapy; Radiotherapy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Diterpenes; Terpenes; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Combined Modality Therapy; Therapeutics; Drug Therapy

Study Officials

• Paula Silverman, MD

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

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 7, 2001
• First Posted: January 27, 2003
• Study Start: November 1, 2001
• Primary Completion: December 1, 2005
• Study Completion: August 1, 2010
• Last Updated: June 17, 2013

Record last verified: 2013-06

Locations

US (5)