NOV-002, Doxorubicin, Cyclophosphamide, and Docetaxel in Women With Newly Diagnosed Stage II or IIIC Breast Cancer
NOV-002, Doxorubicin, Cyclophosphamide, and Docetaxel in Women With Newly Diagnosed Stage II or IIIC Breast Cancer
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.
Inclusion Criteria:

 -  Females age 18 years or older.

 -  The ability to provide written informed consent prior to study specific screening
 procedures, with the understanding that the patient has the right to withdraw from the
 study at any time.

 -  Histologically confirmed infiltrating (invasive) breast cancer by core needle biopsy,
 with no evidence of metastatic disease except to the ipsilateral axillary lymph nodes.

 -  Clinical stage IIB - IIIC (T2-4, N0 or N1, M0 or - any T, N1-3, M0) breast cancer. The
 primary tumor must be greater than or equal to 2 cm (T2-4) or with pathologically
 proven axillary nodal involvement (N1-3).

 -  Patients with inflammatory breast cancer (T4) are permitted into the study.

 -  Clinically palpable tumor that meets the criteria of RECIST for palpable measurable
 disease. The primary tumor must be greater than or equal to 2 cm (T2-4) or with
 pathologically proven axillary nodal involvement (N1-3). Bilateral synchronic breast
 cancers are allowed but one of the primary tumors should be selected as the target
 tumor.

 -  Primary tumor may be estrogen or progesterone receptor negative or positive, and human
 epidermal growth factor receptor 2 (HER-2/neu) negative as determined by either
 Fluorescent In Situ Hybridization (FISH) or 0-2+ staining by immunohistochemistry
 (IHC) (Hercept™).

 -  Normal cardiac ejection fraction (EF ≥ 50%) as determined by screening multigated
 acquisition scan (MUGA) or echocardiogram.

 -  No prior history of myocardial infarction, congestive heart failure, symptomatic
 coronary artery disease, or cardiac arrhythmias.

 -  Patients must be ambulatory with Eastern Cooperative Oncology Group (ECOG) Performance
 Status of 0-1.

 -  The patient or her caregiver must be able to self administer daily subcutaneous
 injections.

 -  Life expectancy greater than 6 months.

 Exclusion Criteria:

 -  Prior therapy of any modality for the treatment of breast cancer

 -  Any prior therapy with an anthracycline or a taxane for any other indication

 -  HER-2 positive breast cancer defined as either gene amplification by Fluorescent In
 Situ Hybridization (FISH) or 3+ staining by IHC (Hercept™).

 -  Women who have a positive pregnancy test, no pregnancy test available, who are
 pregnant or who are lactating.

 -  Women of childbearing potential must agree to use a reliable and appropriate
 contraceptive method, which could include a double barrier method (condom plus
 diaphragm), an intrauterine device or oral contraceptives. Women with ER or PR
 positive breast cancer, should not, however, use oral contraceptives as a method of
 contraception. Postmenopausal women must have been amenorrheic for at least 12 months
 to be considered of non-childbearing potential.

 -  Women with breast cancer that do not have palpable breast tumors at screening.

 -  History of another malignancy within the last 5 years except curatively treated basal
 cell carcinoma of the skin or cervical intraepithelial neoplasia.

 -  Clinically significant (i.e. active) cardiac disease (NYHA Grade II or greater
 congestive heart failure, symptomatic coronary artery disease, unstable angina, and
 cardiac arrhythmia not well-controlled with medication), myocardial infarction within
 the last 6 months prior to study start, or screening ejection fraction of < 50%.

 -  Any of the following abnormal laboratory values:

 -  Absolute neutrophil count < 1.5 x 109/L

 -  Platelet count < 100 x 109/L

 -  Serum bilirubin > 1.5 x upper limit of normal (ULN)

 -  Serum alanine transaminase (ALT), aspartate transaminase (AST) > 2.5 x ULN

 -  Serum creatinine > 2.0 mg/dL or 177mmol/L or calculated creatinine clearance by
 the method of Cockcroft and Gault < 50mL/min).

 -  Any severe or poorly controlled systemic disease (e.g., hypertension; clinically
 significant cardiovascular, pulmonary, or metabolic disease, disorders of
 wound-healing, ulcer or bone fracture).

 -  Patients who have received any investigational treatment within 4 weeks of study
 start.

 -  Known infection with HIV, Hepatitis B virus (HBV), or Hepatitis C virus (HCV).

 -  Known hypersensitivity to any of the components of NOV-002 or to any of the study
 drugs.

 -  Patients assessed by the investigator to be unable or unwilling to comply with the
 requirements of the protocol.