Combination Chemotherapy and Bevacizumab in Treating Women With HER2/Neu-Negative Stage II or Stage III 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: NCT00679029
Recruitment Status : Active, not recruiting
First Posted : May 16, 2008
Last Update Posted : January 25, 2018
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Elizabeth Reed, MD, University of Nebraska

Brief Summary:

RATIONALE: Drugs used in chemotherapy, such as doxorubicin hydrochloride, cyclophosphamide, paclitaxel, and gemcitabine hydrochloride, 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 combination chemotherapy together with bevacizumab after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This phase II trial is studying the side effects and how well giving combination chemotherapy together with bevacizumab works in treating women with HER2/neu-negative stage II or stage III breast cancer

Condition or disease Intervention/treatment Phase
HER2-negative Breast Cancer Stage II Breast Cancer Stage IIIA Breast Cancer Stage IIIB Breast Cancer Stage IIIC Breast Cancer Drug: doxorubicin hydrochloride Drug: cyclophosphamide Biological: bevacizumab Drug: paclitaxel Drug: gemcitabine hydrochloride Other: laboratory biomarker analysis Biological: pegfilgrastim Phase 2

Detailed Description:


I. To assess the feasibility of administering two sequential chemotherapy doublets with Avastin in the adjuvant setting.

II. To assess the safety of Avastin in the adjuvant setting particularly regarding cardiac function, wound healing and toxicity of radiation.


I. To determine the effect of Avastin on immunity, especially VEGF-A upregulation of MDSC and suppression of T-Cells.

II. To determine the effect of therapy on numbers of myeloid derived suppressor cells and compare the humoral and cellular response to p53 in breast cancer patients treated with the same chemotherapy.

III. Patients will be followed for freedom from tumor progression and survival.


COURSES 1-4: Patients receive doxorubicin hydrochloride IV and cyclophosphamide IV on day 1 and pegfilgrastim subcutaneously (SC) on day 1. Treatment repeats every 2 weeks for 4 courses in the absence of unacceptable toxicity or disease progression.

COURSES 5-7: Patients receive paclitaxel IV and gemcitabine hydrochloride IV on day 1 and pegfilgrastim SC on day 1. Patients also receive bevacizumab IV on day 1 in courses 5-7. Treatment repeats every 2 weeks for 4 courses in the absence of unacceptable toxicity or disease progression.

COURSES 8-16: Patients receive bevacizumab IV alone on day 1. Treatment repeats every 3 weeks for 8 courses in the absence of unacceptable toxicity or disease progression.

After course 8, patients may undergo radiotherapy and hormone therapy, if clinically indicated.

After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 5 years.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 26 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Adjuvant Doxorubicin, Cyclophosphamide Followed by Avastin Given With Paclitaxel and Gemcitabine for Stage II and III Breast Cancer That Does Not Over-express HER-2/Neu
Study Start Date : May 2008
Estimated Primary Completion Date : August 2018
Estimated Study Completion Date : August 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Arm I
See Detailed Description
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF

Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana

Biological: bevacizumab
Given IV
Other Names:
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • Avastin
  • rhuMAb VEGF

Drug: paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol

Drug: gemcitabine hydrochloride
Given IV
Other Names:
  • dFdC
  • difluorodeoxycytidine hydrochloride
  • gemcitabine
  • Gemzar

Other: laboratory biomarker analysis
Correlative studies

Biological: pegfilgrastim
Given subcutaneously
Other Names:
  • Filgrastim SD-01
  • GCSF-SD01
  • Neulasta
  • SD-01 sustained duration G-CSF

Primary Outcome Measures :
  1. Feasibility as assessed by the proportion of patients with study drug-associated adverse events leading to dose holds or reductions summarized using percentages and 95% confidence intervals [ Time Frame: At study drug-associated adverse events leading to dose holds or reductions ]
  2. Toxicity as assessed by NCI Common Toxicity Criteria v3.0 [ Time Frame: At the worsening of a concurrent disease or the development of a new concurrent disease ]
  3. Disease-free survival as assessed by the Kaplan and Meier method [ Time Frame: From the date of first treatment to the date of disease progression/recurrence, second cancer, or death ]
  4. Overall survival as assessed by the Kaplan and Meier method [ Time Frame: From the date of first treatment to the date of death ]

Information from the National Library of Medicine

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Ages Eligible for Study:   19 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histological diagnosis of invasive breast cancer: By pathologic evaluation, primary tumor must be T1-4N1-3M0 or T3-4N 0M0 that is ER/PR positive or negative and HER-2/neu negative (1+) immunocytochemistry or not amplified by FISH
  • OR By pathologic evaluation, primary tumor must be T2N0 that is ER, PR and HER-2neu negative
  • Women of reproductive potential must be non-pregnant and non-nursing and must agree to employ an effective barrier method of birth control throughout the study and for up to 6 months following treatment
  • Women of child-bearing potential, must have a negative pregnancy test within 7 days of initiating study (no childbearing potential is defined as age 55 years or older and no menses for two years or any age with surgical removal of the uterus and/or both ovaries)
  • ECOG performance status of 0 or 1
  • Definitive surgery, lumpectomy and axillary sampling or modified radical mastectomy
  • Three weeks since last surgery other than port or right atrial catheter placement
  • No significant cardiac disease and a normal left ventricular ejection fraction
  • No significant open wounds, uncontrolled hypertension, history of venous or arterial clotting
  • Adequate laboratory parameters within 30 days prior to enrollment defined as:
  • Absolute neutrophil count greater than or equal to 1,500/mcl
  • Platelet count equal to or greater than 150,000/mcl
  • Hemoglobin >11gm/dl
  • Alkaline phosphatase equal or less than 1.5 times the ULN
  • Total bilirubin equal to or less than 1.5 times the ULN
  • AST and ALT no greater than 1.5 times the ULN
  • Creatinine less than 1.5 times the ULN
  • Urine protein < 2+ on urinalysis, UPC 1.0 or 24 hour urine < 1 g protein
  • No active serious infections or other condition precluding chemotherapy
  • Able to give informed consent
  • Able to return for treatment and follow-up on the specified days

Exclusion Criteria:

  • Prior malignancy; except for adequately treated basal cell or squamous cell skin cancer or noninvasive carcinomas, or other cancer from which the patient has been disease free for 5 years
  • Prior chemotherapy or radiation therapy
  • Breast cancer that over expresses Her-2/neu
  • Stage IV or metastatic breast cancer
  • Inability to cooperate with treatment protocol
  • Any comorbidity or condition which, in the opinion of the investigator, may interfere with the assessments and procedures of this protocol
  • Inadequately controlled hypertension (defined as systolic blood pressure > 150 and/or diastolic blood pressure > 100 mmHg on antihypertensive medications
  • Any prior history of hypertensive crisis or hypertensive encephalopathy
  • New York Heart Association (NYHA) Grade II or greater congestive heart failure
  • History of myocardial infarction or unstable angina within 12 months of study enrollment
  • Any history of stroke or transient ischemic attack at any time
  • Significant vascular disease (e.g., aortic aneurysm, aortic dissection)
  • Symptomatic peripheral vascular disease
  • Evidence of bleeding diathesis or coagulopathy
  • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment
  • Serious, non-healing wound, ulcer, or bone fracture
  • Proteinuria at screening as demonstrated by either urine protein/creatinine (UPC) ratio >= 1.0 at screening OR urinalysis for proteinuria >= 2+ (patients discovered to have >= 2+ proteinuria on urinalysis at baseline and undergo a 24 hour urine collection and demonstrate > 1g of protein in 24 hours are ineligible)
  • Known hypersensitivity to any component of Avastin or gemcitabine or other required drugs in the study
  • History of venous or arterial thrombosis
  • Current, ongoing treatment with full-dose warfarin or its equivalent (i.e., unfractionated and/or low molecular weight heparin) for any reason (ASA okay)

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): NCT00679029

United States, Nebraska
UNMC Eppley Cancer Center at the University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198-6805
Sponsors and Collaborators
University of Nebraska
National Cancer Institute (NCI)
Principal Investigator: Elizabeth Reed University of Nebraska

Responsible Party: Elizabeth Reed, MD, Medical Oncologist, University of Nebraska Identifier: NCT00679029     History of Changes
Other Study ID Numbers: 412-07
NCI-2009-01693 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
P30CA036727 ( U.S. NIH Grant/Contract )
First Posted: May 16, 2008    Key Record Dates
Last Update Posted: January 25, 2018
Last Verified: January 2018

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Liposomal doxorubicin
Albumin-Bound Paclitaxel
Antibodies, Monoclonal
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors