NOV-002, Doxorubicin, Cyclophosphamide, and Docetaxel in Women With Newly Diagnosed Stage II or IIIC Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Cyclophosphamide; Docetaxel; Doxorubicin; NOV 002
Intervention MeSH terms: Cyclophosphamide; Docetaxel; Doxorubicin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 41.0
Sex: Female
Minimum age: 18 Years
Maximum age: 120 Years
Healthy volunteers: No
Keywords: stage II breast cancer; stage IIIC breast cancer; inflammatory breast cancer

Summary:

      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.
    

Eligibility criteria:

        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.