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Phase II Study of Neoadjuvant Treatment With NOV-002 in Combination With Doxorubicin and Cyclophosphamide Followed by Docetaxel in Patients With Stages IIB-IIIC Breast Cancer

Phase 2
18 Years
Not Enrolling
Breast Cancer

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Trial Information

Phase II Study of Neoadjuvant Treatment With NOV-002 in Combination With Doxorubicin and Cyclophosphamide Followed by Docetaxel in Patients With Stages IIB-IIIC Breast Cancer



- 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.


- Define the safety profiles of preoperative administration of NOV-002 in combination
with doxorubicin hydrochloride and cyclophosphamide followed by docetaxel.

- Correlate serum protein glutathionylation with clinical and pathologic responses.

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

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


- Histologically confirmed infiltrating (i.e., invasive) breast cancer

- Newly diagnosed disease

- Clinical stage IIB or IIIC (T2-4, N0 or N1, M0) or (any T, N1-3, M0) disease, as
defined by 1 of the following criteria:

- Primary tumor ≥ 2 cm (T2-4)

- Pathologically-proven axillary nodal involvement (N1-3)

- No evidence of metastatic disease except to the ipsilateral axillary lymph nodes

- Disease confirmed by core needle biopsy

- Inflammatory breast cancer (T4) allowed

- Clinically palpable disease that is measurable by RECIST AND meets 1 of the following
staging criteria:

- Primary tumor ≥ 2 cm (T2-4)

- Bilateral synchronic breast cancers allowed, provided 1 of the primary
tumors is selected as the target tumor

- Pathologically-proven axillary nodal involvement (N1-3)

- HER-2/neu negative by FISH or 0-2 positive staining by IHC

- Hormone-receptor status:

- Estrogen or progesterone receptor-negative or -positive


- Female

- Menopausal status not specified

- ECOG performance status 0-1

- Life expectancy > 6 months

- ANC ≥ 1,500/mm³

- Platelet count ≥ 1,000/mm³

- Bilirubin ≤ 1.5 times upper limit of normal (ULN)

- AST or ALT ≤ 2.5 times ULN

- INR ≤ 1.5

- Creatinine ≤ 2 mg/dL or 177 mmol/L OR calculated creatinine clearance ≥ 50 mL/min

- Cardiac ejection fraction ≥ 50% by baseline MUGA or ECHO

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No other malignancy within the past 5 years except curatively treated basal cell
carcinoma of the skin or cervical intraepithelial neoplasia

- No prior or concurrent clinically significant (i.e., active) cardiac disease,
including any of the following:

- New York Heart Association grade II-IV congestive heart failure

- Symptomatic coronary artery disease

- Unstable angina

- Cardiac arrhythmia not well-controlled with medication

- Myocardial infarction within the past 6 months

- No severe or poorly controlled systemic disease (e.g., hypertension; clinically
significant cardiovascular, pulmonary, or metabolic disease, disorders of
wound-healing, ulcer, or bone fracture)

- No known HIV, HBV, or HCV infection

- No known hypersensitivity to any of the components of oxidized glutathione (NOV-002)
or to any of the other study drugs

- Patient or caregiver must be able to administer daily subcutaneous injections


- No prior primary systemic or local treatment for breast cancer, including surgery,
radiotherapy, chemotherapy, hormonal therapy, or biological therapy

- No prior anthracycline- or taxane-based therapy for any other indication

- More than 4 weeks since prior and no other concurrent investigational treatment

- No other concurrent investigational agent

- No other concurrent cytotoxic chemotherapy or hormonal agent

- No other concurrent antineoplastic therapy including, but not limited to,
immunotherapy, monoclonal antibody therapy, or targeted agents

- No concurrent localized or partial breast radiotherapy

- No other concurrent radiotherapy during the period of study drug administration

- No concurrent growth factors for primary prophylaxis during the first course of

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Percentage of Participants Achieving Pathologic Complete Response

Outcome Description:

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.

Outcome Time Frame:

4 years

Safety Issue:


Principal Investigator

Keisuke Shirai, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Medical University of South Carolina


United States: Food and Drug Administration

Study ID:




Start Date:

May 2007

Completion Date:

April 2011

Related Keywords:

  • Breast Cancer
  • stage II breast cancer
  • stage IIIC breast cancer
  • inflammatory breast cancer
  • Breast Neoplasms



Hollings Cancer Center at Medical University of South Carolina Charleston, South Carolina  29425
University of Miami Sylvester Comprehensive Cancer Center - Miami Miami, Florida  33136