COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC:

Get the latest research information from NIH: Menu

Bevacizumab, Doxorubicin, and Cyclophosphamide Followed By Paclitaxel Albumin-Stabilized Nanoparticle Formulation and Bevacizumab in Treating Patients Who Have Undergone Surgery for Early-Stage Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00436709
Recruitment Status : Unknown
Verified June 2007 by National Cancer Institute (NCI).
Recruitment status was:  Active, not recruiting
First Posted : February 19, 2007
Last Update Posted : January 6, 2014
National Cancer Institute (NCI)
Information provided by:
National Cancer Institute (NCI)

Brief Summary:

RATIONALE: 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. Drugs used in chemotherapy, such as doxorubicin, cyclophosphamide, and paclitaxel albumin-stabilized nanoparticle formulation, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bevacizumab together with chemotherapy after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This clinical trial is studying the side effects and how well giving bevacizumab together with doxorubicin and cyclophosphamide followed by paclitaxel albumin-stabilized nanoparticle formulation and bevacizumab works in treating patients who have undergone surgery for early-stage breast cancer.

Condition or disease Intervention/treatment Phase
Breast Cancer Biological: bevacizumab Biological: pegfilgrastim Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: paclitaxel albumin-stabilized nanoparticle formulation Other: flow cytometry Other: immunoenzyme technique Other: immunologic technique Other: laboratory biomarker analysis Procedure: adjuvant therapy Procedure: immunoscintigraphy Not Applicable

Detailed Description:



  • Determine the cardiac safety of adjuvant concurrent bevacizumab and dose-dense doxorubicin hydrochloride and cyclophosphamide followed by dose-dense paclitaxel albumin-stabilized nanoparticle formulation and maintenance therapy comprising bevacizumab alone in patients with early-stage breast cancer.


  • Determine the noncardiac toxicity of this regimen in these patients.
  • Determine the efficacy of this regimen, in terms of time to tumor recurrence and overall survival, in these patients.
  • Explore changes in circulating endothelial cells and circulating tumor cells from pre-treatment levels in patients with no evidence of disease.
  • Prospectively explore the use of serial troponin I as a predictor of cardiac toxicity in patients treated with this regimen.
  • Prospectively explore the relationship between plasma renin activity and hypertension in patients treated with bevacizumab and chemotherapy.

OUTLINE: This is a nonrandomized, pilot, multicenter study.

Patients receive doxorubicin hydrochloride IV, cyclophophamide IV, and bevacizumab IV over 30-90 minutes on day 1 and pegfilgrastim subcutaneously (SC) on day 2. Treatment repeats every 2 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Patients then receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on day 1 and pegfilgrastim SC on day 2. Treatment with paclitaxel albumin-stabilized nanoparticle formulation and pegfilgrastim repeats every 2 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance therapy comprising bevacizumab IV over 30-90 minutes on day 1. Treatment with maintenance therapy repeats every 3 weeks for 12 courses in the absence of disease progression or unacceptable toxicity.

Blood samples are collected at baseline and periodically during study treatment. Samples are analyzed for circulating endothelial cells (by flow cytomery [FC]), circulating epithelial cells (by immunocytochemistry and FC), troponin I concentrations (by enzyme immunoassay or chemiluminescent microparticle immunoassay), and plasma renin activity (by radioimmunoassay).

After completion of study treatment, patients are followed every 4-6 months for 3 years, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 75 patients will be accrued for this study.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 75 participants
Allocation: Non-Randomized
Primary Purpose: Treatment
Official Title: A Pilot Study of Bevacizumab With Dose Dense Doxorubicin and Cyclophosphamide (AC) Followed by Dose Dense Nanoparticle Albumin Bound Paclitaxel for the Treatment of Early Stage Breast Cancer
Study Start Date : July 2006

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Primary Outcome Measures :
  1. Safety

Secondary Outcome Measures :
  1. Noncardiac toxicity
  2. Time to tumor recurrence
  3. Overall survival

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically or cytologically confirmed invasive breast cancer meeting the following criteria:

    • Early-stage disease

      • No stage IV disease
    • More than one synchronous primary breast tumor
    • Lymph node positive OR high-risk lymph node negative
  • Candidate for treatment with anthracycline- and taxane-based chemotherapy in the adjuvant setting

    • Must begin therapy within 84 days after the final required surgical procedure
  • HER2/neu-negative breast cancer, defined as an immunohistochemistry (IHC) score of 0, 1+ or 2+ and fluorescent in situ hybridization (FISH) not amplified
  • No CNS disease (e.g., primary brain tumor or brain metastasis)
  • Hormone receptor status known


  • Male or female
  • Pre- or post-menopausal
  • ECOG performance status 0-1
  • Absolute neutrophil count ≥ 1,000/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Bilirubin normal
  • AST or ALT ≤ 2.5 times upper limit of normal
  • Creatinine normal OR creatinine clearance ≥ 60 mL/min
  • Urine protein:creatinine ratio ≤ 1.0
  • PT and PTT normal
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 6 months after completion of study therapy
  • LVEF normal by MUGA scan at baseline
  • No significant bleeding within the past 6 months
  • No uncontrolled underlying bleeding diathesis
  • No nonmalignant systemic disease (e.g., cardiovascular, renal, or hepatic) that would preclude study therapy, including any of the following conditions:

    • Blood pressure > 150/100 mm Hg
    • Unstable angina
    • New York Heart Association class II -IV congestive heart failure
    • Myocardial infarction or stroke within the past 12 months
    • Clinically significant peripheral vascular disease
  • No seizures not controlled with standard medical therapy
  • No history of stroke
  • No known allergy or hypersensitivity to study drugs (prior hypersensitivity to paclitaxel allowed)
  • No significant traumatic injury within the past 28 days
  • No serious nonhealing wound, ulcer, or bone fracture
  • No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
  • No active gastroduodenal ulcer
  • No uncontrolled intercurrent illness, including psychiatric illness or social situation that would limit compliance with study requirements


  • See Disease Characteristics
  • Prior therapy for an ipsilateral or contralateral breast cancer primary allowed provided the following criteria are met:

    • No prior anthracycline therapy
    • Prior hormonal therapy for this previous breast cancer is allowed, but must be stopped during study therapy
    • At least 1 year since prior taxane therapy
  • More than 28 days since prior and no concurrent major surgery or open biopsy

    • Anticipated reconstructive surgery (e.g., tissue expander exchange) is allowed during the course of the study (bevacizumab will be held during that time as per protocol guidelines)
  • More than 7 days since prior minor surgery, including fine-needle aspiration or core biopsy

    • At least 24 hours since prior indwelling catheter placement
  • No prior bevacizumab or other KDR inhibitors (e.g., VEGF Trap, semaxanib, SU6668, vandetanib, vatalanib, AEE788, or IMC-1CII)
  • No concurrent full-dose anticoagulation therapy
  • No concurrent hormonal therapy as chemoprevention
  • Concurrent participation in adjuvant hormone therapy or correlative or companion (e.g., bisphosphonate clinic) studies allowed
  • No other concurrent anticancer therapy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00436709

Layout table for location information
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
National Cancer Institute (NCI)
Layout table for investigator information
Study Chair: Maura N. Dickler, MD Memorial Sloan Kettering Cancer Center
Layout table for additonal information Identifier: NCT00436709    
Other Study ID Numbers: CDR0000529855
First Posted: February 19, 2007    Key Record Dates
Last Update Posted: January 6, 2014
Last Verified: June 2007
Keywords provided by National Cancer Institute (NCI):
male breast cancer
stage I breast cancer
stage II breast cancer
stage IIIA breast cancer
Additional relevant MeSH terms:
Layout table for MeSH terms
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Liposomal doxorubicin
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Myeloablative Agonists
Antineoplastic Agents, Immunological
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antibiotics, Antineoplastic