RATIONALE: Oxidized glutathione (NOV-002) may stimulate the immune system in different ways and stop tumor cells from growing. Drugs used in chemotherapy, such as doxorubicin, cyclophosphamide, and docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Giving NOV-002 together with chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. PURPOSE: This phase II trial is studying how well giving oxidized glutathione (NOV-002) together with doxorubicin and cyclophosphamide followed by docetaxel works in treating women with newly diagnosed stage II or stage III breast cancer.
OUTLINE: This is a multicenter study. Patients receive oxidized glutathione (NOV-002) IV twice on day -1 of course 1 and once on day 1 of courses 2-8. Patients receive NOV-002 subcutaneously once daily on days 2-21 of courses 1-8. Patients also receive chemotherapy comprising doxorubicin hydrochloride IV and cyclophosphamide IV on day 1 of courses 1-4 followed by docetaxel IV on day 1 of courses 5-8. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo definitive surgery 3-6 weeks after completion of neoadjuvant therapy. Blood samples are obtained at baseline and periodically during study to measure serum and plasma protein glutathionlylation. Additional blood samples are collected from some patients for immunological correlative studies. After completion of study therapy, patients are followed at 30 days.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
41
University of Miami
Miami, Florida, United States
Hollings Cancer Center at Medical University of South Carolina
Charleston, South Carolina, United States
Rate of Pathologic Complete Response in the Affected Breast After Protocol Therapy
The primary objective of this study is to define the rate of pathologic complete response rate (pCR) in the affected breast after the preoperative administration of NOV-002 in combination with doxorubicin and cyclophosphamide followed by docetaxel in patients with stage IIB-IIIC breast cancer. Pathologic complete response (pCR) is defined according to Hankoop et al \[41\] as either: the absence of any histological evidence of invasive breast cancer cells in the tissue specimen removed from the breast or the presence of invasive tumor equal to or less than 10mm after preoperative treatment, determined at definitive breast surgery.
Time frame: About 7 months
Definition of the Safety Profiles of Protocol Therapy
Definition of the safety profiles of protocol therapy in study participants as shown by the number of study participants experiencing adverse events or other toxicity.
Time frame: Up to 30 days Post-Last Dose of Protocol Therapy, About 7 months
Correlation Between Myeloid Derived Suppressor Cell (MDSC) Levels and Pathologic Complete Response (pCR) and Non-Responders
The investigators hypothesized that patients with favorable responses, i.e. pCR, are more likely to have significantly lower levels of MDSCs than non-responders. MDSC levels will be measured at baseline and on day 1 of each treatment cycle, cycles 1 through 8.
Time frame: Baseline, Day 1 of Cycles 1 through 8, about 7 months
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