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Doxorubicin, Cyclophosphamide, and Paclitaxel With or Without Bevacizumab in Treating Patients With Lymph Node-Positive or High-Risk, Lymph Node-Negative Breast Cancer
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), January 2009
Sponsors and Collaborators: Eastern Cooperative Oncology Group
National Cancer Institute (NCI)
North Central Cancer Treatment Group
Cancer and Leukemia Group B
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00433511
  Purpose

RATIONALE: Drugs used in chemotherapy, such as doxorubicin, cyclophosphamide, and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of breast cancer by blocking blood flow to the tumor. Giving chemotherapy together with bevacizumab after surgery may kill any tumor cells that remain after surgery. It is not yet known whether doxorubicin, cyclophosphamide, and paclitaxel are more effective with or without bevacizumab in treating breast cancer.

PURPOSE: This randomized phase III trial is studying doxorubicin, cyclophosphamide, and paclitaxel to see how well they work with or without bevacizumab in treating patients with lymph node-positive or high-risk, lymph node-negative breast cancer.


Condition Intervention Phase
Breast Cancer
Drug: bevacizumab
Drug: cyclophosphamide
Drug: paclitaxel
Drug: pegylated liposomal doxorubicin hydrochloride
Drug: placebo
Phase III

Genetics Home Reference related topics: breast cancer
MedlinePlus related topics: Breast Cancer Cancer
Drug Information available for: Doxorubicin Doxorubicin hydrochloride Cyclophosphamide Paclitaxel Bevacizumab
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized, Open Label, Placebo Control
Official Title: A Double-Blind Phase III Trial of Doxorubicin and Cyclophosphamide Followed by Paclitaxel With Bevacizumab or Placebo in Patients With Lymph Node Positive and High Risk Lymph Node Negative Breast Cancer

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Disease-free survival (DFS) [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Efficacy of short-term vs long-term bevacizumab, in terms of DFS [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]

Estimated Enrollment: 4950
Study Start Date: November 2007
Estimated Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Arm I: Active Comparator
Patients receive doxorubicin hydrochloride IV, cyclophosphamide IV over 20-30 minutes, and placebo IV over 30-90 minutes on day 1. Treatment repeats every 2 or 3 weeks for 4 courses. Patients then receive paclitaxel IV over 1 hour on days 1, 8, and 15 and placebo IV over 30-90 minutes on day 1. Treatment with paclitaxel and placebo repeats every 3 weeks for 4 courses.
Drug: cyclophosphamide
Given IV
Drug: paclitaxel
Given IV
Drug: pegylated liposomal doxorubicin hydrochloride
Given IV
Drug: placebo
Given IV over 30-90 minutes
Arm II: Experimental
Patients receive doxorubicin hydrochloride and cyclophosphamide as in arm I and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 2 or 3 weeks for 4 courses. Patients then receive paclitaxel as in arm I and bevacizumab IV over 30-90 minutes on day 1. Treatment with paclitaxel and bevacizumab repeats every 3 weeks for 4 courses.
Drug: bevacizumab
Given IV
Drug: cyclophosphamide
Given IV
Drug: paclitaxel
Given IV
Drug: pegylated liposomal doxorubicin hydrochloride
Given IV
Arm III: Experimental
Patients receive doxorubicin hydrochloride and cyclophosphamide as in arm I and bevacizumab as in arm II. Treatment repeats every 2 or 3 weeks for 4 courses. Patients then receive paclitaxel as in arm I and bevacizumab as in arm II. Treatment with paclitaxel and bevacizumab repeats every 3 weeks for 4 courses. Patients then receive open-label bevacizumab IV over 30-90 minutes on day 1. Treatment with bevacizumab alone repeats every 3 weeks for 10 courses.
Drug: bevacizumab
Given IV
Drug: cyclophosphamide
Given IV
Drug: paclitaxel
Given IV
Drug: pegylated liposomal doxorubicin hydrochloride
Given IV

Detailed Description:

OBJECTIVES:

Primary

  • Compare the disease-free survival (DFS) of patients with lymph node-positive or high-risk, lymph node-negative breast cancer treated with adjuvant therapy comprising doxorubicin hydrochloride, cyclophosphamide, and paclitaxel with vs. without bevacizumab.

Secondary

  • Compare the overall survival of patients treated with these regimens.
  • Determine the toxicity of these regimens.
  • Compare the efficacy of short-term (20-24 weeks) vs long-term (50-54 weeks) bevacizumab, in terms of DFS, in these patients.

OUTLINE: This is a randomized, partially double-blind, placebo-controlled, partially open-label, multicenter study. Patients are stratified according to planned dose schedule of doxorubicin hydrochloride and cyclophosphamide (every 3 weeks vs every 2 weeks). Patients are further stratified according to estrogen receptor status (positive vs negative), lymph node involvement (node-negative vs 1-3 positive node[s] vs ≥ 4 positive nodes), and received/planned treatment (lumpectomy and whole breast radiation therapy vs lumpectomy and accelerated partial-breast radiation therapy [before or after chemotherapy] vs mastectomy with no planned radiation therapy vs mastectomy with planned radiation therapy). Patients are randomized to 1 of 3 treatment arms (20% of patients are randomized to Arm I, 40% to Arm II, and 40% to Arm III).

  • Arm I: Patients receive doxorubicin hydrochloride IV, cyclophosphamide IV over 20-30 minutes, and placebo IV over 30-90 minutes on day 1. Treatment repeats every 2 or 3 weeks for 4 courses. Patients then receive paclitaxel IV over 1 hour on days 1, 8, and 15 and placebo IV over 30-90 minutes on day 1. Treatment with paclitaxel and placebo repeats every 3 weeks for 4 courses.
  • Arm II: Patients receive doxorubicin hydrochloride and cyclophosphamide as in arm I and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 2 or 3 weeks for 4 courses. Patients then receive paclitaxel as in arm I and bevacizumab IV over 30-90 minutes on day 1. Treatment with paclitaxel and bevacizumab repeats every 3 weeks for 4 courses.
  • Arm III: Patients receive doxorubicin hydrochloride and cyclophosphamide as in arm I and bevacizumab as in arm II. Treatment repeats every 2 or 3 weeks for 4 courses. Patients then receive paclitaxel as in arm I and bevacizumab as in arm II. Treatment with paclitaxel and bevacizumab repeats every 3 weeks for 4 courses. Patients then receive open-label bevacizumab IV over 30-90 minutes on day 1. Treatment with bevacizumab alone repeats every 3 weeks for 10 courses.

In all arms, treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for up to 15 years.

PROJECTED ACCRUAL: A total of 4,950 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed adenocarcinoma of the breast

    • Significant risk of distant recurrence based on ≥ 1 of the following criteria:

      • At least 1 axillary lymph node (LN) positive on routine histologic examination (must be demonstrated by more than immunohistochemistry alone)
      • LN negative with estrogen receptor (ER)-negative tumor ≥ 1 cm
      • LN negative with ER+ tumor ≥ 5 cm regardless of recurrence score
      • LN negative with ER+ tumor ≥ 1 cm but < 5 cm with a recurrence score ≥ 11

        • Patients enrolled on ECOG-PACCT-1 clinical trial are eligible
  • Has undergone definitive breast surgery within the past 29-84 days, including total mastectomy and axillary dissection (modified radical mastectomy), total mastectomy and sentinel node biopsy, lumpectomy and axillary dissection, or lumpectomy and sentinel node biopsy

    • Surgical margins must be histologically free of invasive breast cancer and ductal carcinoma in situ

      • Resection margins positive for lobular carcinoma in situ allowed
  • Planned post-lumpectomy radiation therapy required, including any of the following:

    • Whole breast radiation therapy after chemotherapy
    • Accelerated partial breast radiation therapy after chemotherapy
    • Accelerated partial breast radiation therapy prior to chemotherapy
  • Planned post-mastectomy radiation therapy required for patients with a primary tumor of ≥ 5 cm or involvement of ≥ 4 lymph nodes
  • No HER2/neu positive breast cancer (i.e., 3+ by immunohistochemistry or positive by fluorescent in situ hybridization [FISH])
  • No clinical evidence of inflammatory disease or fixed axillary nodes (N2) at diagnosis
  • May have synchronous bilateral breast cancer (diagnosed ≤ 1 month) if the higher TNM stage tumor meets the eligibility criteria for this trial
  • Hormone receptor status known

PATIENT CHARACTERISTICS:

  • Male or female
  • Pre- or post-menopausal
  • ECOG performance status 0-1
  • Absolute neutrophil count ≥ 1,000/mm³
  • Platelet count ≥ 100,000/mm³
  • Bilirubin ≤ 1.5 mg/dL
  • AST ≤ 2 times upper limit of normal (ULN)
  • Creatinine ≤ 1.5 mg/dL
  • Urine protein:creatinine ratio < 1.0
  • PTT ≤ 1.5 times ULN
  • LVEF normal by echocardiogram or MUGA
  • No clinically significant cardiovascular or cerebrovascular disease, including any of the following:

    • Uncontrolled arrhythmia

      • Controlled atrial fibrillation allowed
    • Uncontrolled hypertension, defined as systolic blood pressure (BP) > 160 mm Hg or diastolic BP > 90 mm Hg
    • Transient ischemic attack, stroke, or subarachnoid hemorrhage
    • Ischemic bowel
    • Myocardial infarction within the past 12 months
    • Unstable angina within the past 12 months
    • New York Heart Association class II-IV congestive heart failure within the past 12 months
    • Peripheral vascular disease ≥ grade 2 within the past 12 months
  • No bleeding diathesis, hereditary or acquired bleeding disorder, or coagulopathy
  • No nonhealing wound or fracture
  • No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
  • No hypersensitivity to paclitaxel or drugs using the vehicle Cremophor EL, Chinese hamster ovary cell products, or other recombinant human antibodies
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for ≥ 3 months after completion of study treatment

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • More than 28 days since prior major surgery

    • Nonoperative biopsy not considered major surgery
  • More than 24 hours since prior placement of a vascular access device
  • No prior cytotoxic chemotherapy or hormonal therapy for study cancer

    • May have received prior (but no concurrent) tamoxifen or raloxifene for chemoprevention
  • No prior anthracycline, anthracenedione, or taxane for any condition
  • Concurrent full-dose anticoagulation allowed provided the following criteria are met:

    • INR in-range (usually between 2 and 3) on a stable dose of warfarin or low molecular weight heparin
    • No active bleeding or pathological conditions that carry a high risk of bleeding (e.g., varices)
  • Concurrrent prophylactic anticoagulants to maintain patency of a vascular access device allowed
  • No concurrent cardioprotectant drugs
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00433511

  Show 650 Study Locations
Sponsors and Collaborators
Eastern Cooperative Oncology Group
North Central Cancer Treatment Group
Cancer and Leukemia Group B
Investigators
Study Chair: Kathy Miller, MD Indiana University Melvin and Bren Simon Cancer Center
Investigator: Ramona Swaby, MD Fox Chase Cancer Center
Study Chair: Donald W. Northfelt, MD, FACP Mayo Clinic Scottsdale
Investigator: Chau T. Dang, MD Memorial Sloan-Kettering Cancer Center
  More Information

Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

Study ID Numbers: CDR0000528955, ECOG-E5103
Study First Received: February 8, 2007
Last Updated: January 10, 2009
ClinicalTrials.gov Identifier: NCT00433511  
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
male breast cancer
stage I breast cancer
stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer

Study placed in the following topic categories:
Skin Diseases
Breast Neoplasms, Male
Paclitaxel
Breast Neoplasms
Bevacizumab
Cyclophosphamide
Doxorubicin
Breast Diseases

Additional relevant MeSH terms:
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Growth Substances
Mitosis Modulators
Physiological Effects of Drugs
Antimitotic Agents
Antibiotics, Antineoplastic
Angiogenesis Inhibitors
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Neoplasms by Site
Therapeutic Uses
Tubulin Modulators
Myeloablative Agonists
Growth Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Antineoplastic Agents, Phytogenic
Alkylating Agents

ClinicalTrials.gov processed this record on January 13, 2009