This phase II trial studies how well giving sunitinib malate together with paclitaxel, doxorubicin hydrochloride, and cyclophosphamide before surgery works in treating patients with stage IIB-IIIC breast cancer. Sunitinib malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth or by blocking blood flow to the tumor. Drugs used in chemotherapy, such as paclitaxel, doxorubicin hydrochloride, and cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving sunitinib malate together with combination chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed
PRIMARY OBJECTIVES: I.To assess the microscopic pathologic complete response rate (pCR) in patients treated with a two part, neoadjuvant regimen consisting of daily oral sunitinib with weekly IV paclitaxel for 12 weeks followed by weekly doxorubicin and daily oral cyclophosphamide given with filgrastim (G-CSF) support for 15 weeks. SECONDARY OBJECTIVES: I. To assess the association between microscopic pCR and clinical complete response rate at the primary tumor site. II. To assess the relapse rate, overall and disease-free survival in patients with breast cancer treated with neoadjuvant chemotherapy consisting of daily oral sunitinib with weekly IV paclitaxel for 12 weeks followed weekly doxorubicin and daily oral cyclophosphamide given with G-CSF support for 15 weeks. III. To assess the toxicity associated with these regimens. IV. To explore the relationship between planned correlative laboratory and clinical studies and indicators of efficacy such as pathologic response, clinical response and relapse. OUTLINE: Patients receive neoadjuvant chemotherapy comprising sunitinib malate orally (PO) once daily and paclitaxel intravenously (IV) over 1 hour once weekly for 8-12 weeks in the absence of disease progression or unacceptable toxicity. Beginning within 3 weeks of completion of sunitinib malate and paclitaxel, patients receive doxorubicin IV once weekly for 15 weeks, cyclophosphamide PO once daily for 15 weeks, and filgrastim subcutaneously (SC) on days 2-7 for 16 weeks in the absence of disease progression or unacceptable toxicity. Beginning 3-6 weeks after completion of chemotherapy, patients undergo surgery. After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
68
Given PO
Given IV
Given IV
Given PO
Given SC
Undergo surgery
Correlative studies
Correlative studies
Anchorage Oncology Centre
Anchorage, Alaska, United States
Katmai Oncology Group
Anchorage, Alaska, United States
Arizona Cancer Center
Tucson, Arizona, United States
Saint Luke's Mountain States Tumor Institute
Boise, Idaho, United States
Skagit Valley Hospital
Mount Vernon, Washington, United States
Olympic Medical Center
Port Angeles, Washington, United States
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States
Microscopic Pathologic CR (pCR) Rate
Defined as no evidence of microscopic invasive tumor present at primary tumor site in the surgical specimen and calculated with exact 90% binomial confidence interval.
Time frame: At the time of surgery
Clinical Complete Response and Correlation With Plasma VEGF, Soluble VCAM (sVCAM), and Circulating Endothelial Cells (CECs) Levels
Time frame: At baseline, after week 12 of therapy, and prior to surgery
Relapse Rate
Cumulative incidence rate of relapse, assessed at two years. Death is considered a competing risk.
Time frame: Up to two years
Time to Disease Progression
Median time to disease progression, at two years, as defined by clear increase in disease sites present at registration or development of new disease sites.
Time frame: Up to 2 years
Overall Survival
Kaplan-Meier estimate from the start of protocol therapy until the date of death from any cause or the last date the patient was known to be alive, assessed at two years.
Time frame: Up to 2 years
Number and Percent of Subjects Reporting Adverse Events
See Adverse Events section for more details.
Time frame: 28 days after the last dose of study drug
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