Clinical trial NCT00679029
Conditions: HER2-negative Breast Cancer Stage II Breast Cancer Stage IIIA Breast Cancer Stage IIIB Breast Cancer Stage IIIC Breast Cancer
Sponsor: University of Nebraska
Start date: 2008-05-02; Completion date: 2010-11-18
Enrollment: 15 participants; Allocation: NA; Intervention model: SINGLE_GROUP

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

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 Vascular endothelial growth factor A (VEGF-A) upregulation of myeloid-derived suppressor cells (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.

Arms: arm 1: Doxorubicin 60 mg /M2 followed by cyclophosphamide 600 mg/M2 (AC) will be given every 2 weeks for cycles 1-4.

Paclitaxel 175 mg/M2 followed by gemcitabine 1500 mg/M2 (TG) will be given every 2 weeks for cycles 5-8.

Beginning cycle 5, B1= Avastin 10 mg/kg will be given as a single IV dose following each TG treatment every 2 weeks for cycles 5-7.
Interventions: intervention 1: doxorubicin hydrochloride intervention 2: cyclophosphamide intervention 3: bevacizumab intervention 4: paclitaxel intervention 5: gemcitabine hydrochloride intervention 6: laboratory biomarker analysis intervention 7: pegfilgrastim
Intervention descriptions: intervention 1: Given IV intervention 2: Given IV intervention 3: Given IV intervention 4: Given IV intervention 5: Given IV intervention 6: Correlative studies intervention 7: Given subcutaneously

Protocol documents: