Combination Chemotherapy and Bevacizumab in Treating Women With HER2/Neu-Negative Stage II or Stage III Breast Cancer
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
HER2-negative Breast Cancer
Stage II Breast Cancer
Stage IIIA Breast Cancer
Stage IIIB Breast Cancer
Stage IIIC Breast Cancer
Drug: doxorubicin hydrochloride
Drug: gemcitabine hydrochloride
Other: laboratory biomarker analysis
|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|
- 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 ]
|Study Start Date:||May 2008|
|Estimated Primary Completion Date:||December 2013 (Final data collection date for primary outcome measure)|
Experimental: Arm I
See Detailed Description
Drug: doxorubicin hydrochloride
Other Names:Drug: cyclophosphamide
Other Names:Biological: bevacizumab
Other Names:Drug: paclitaxel
Other Names:Drug: gemcitabine hydrochloride
Other Names:Other: laboratory biomarker analysis
Correlative studiesBiological: pegfilgrastim
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.
|United States, Nebraska|
|UNMC Eppley Cancer Center at the University of Nebraska Medical Center|
|Omaha, Nebraska, United States, 68198-6805|
|Principal Investigator:||Elizabeth Reed||University of Nebraska|