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

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.