Combination Chemotherapy and Bevacizumab in Treating Women With HER2/Neu-Negative Stage II or Stage III Breast Cancer

The recruitment status of this study is unknown because the information has not been verified recently.
Verified August 2011 by University of Nebraska.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Information provided by:
University of Nebraska
ClinicalTrials.gov Identifier:
NCT00679029
First received: May 15, 2008
Last updated: August 8, 2011
Last verified: August 2011
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by University of Nebraska:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
  • Overall survival as assessed by the Kaplan and Meier method [ Time Frame: From the date of first treatment to the date of death ] [ Designated as safety issue: No ]

Estimated Enrollment: 26
Study Start Date: May 2008
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

Detailed Description:

PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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.

OUTLINE:

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.

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00679029

Locations
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
Investigators
Principal Investigator: Elizabeth Reed University of Nebraska
  More Information

No publications provided

Responsible Party: Reed, Elizabeth, UNMC Eppley Cancer Center at the University of Nebraska Medical Center
ClinicalTrials.gov Identifier: NCT00679029     History of Changes
Other Study ID Numbers: 412-07, NCI-2009-01693, P30CA036727
Study First Received: May 15, 2008
Last Updated: August 8, 2011
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Antibodies
Antibodies, Monoclonal
Cyclophosphamide
Gemcitabine
Liposomal doxorubicin
Bevacizumab
Doxorubicin
Paclitaxel
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Immunosuppressive Agents
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Antimetabolites, Antineoplastic
Antimetabolites

ClinicalTrials.gov processed this record on August 21, 2014