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Oxidized Glutathione (NOV-002), Doxorubicin, Cyclophosphamide, and Docetaxel in Treating Women With Newly Diagnosed Stage IIB, or Stage IIIC Breast Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of Miami Sylvester Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00499122
First received: July 10, 2007
Last updated: July 25, 2014
Last verified: August 2013

July 10, 2007
July 25, 2014
May 2007
April 2011   (final data collection date for primary outcome measure)
Percentage of Participants Achieving Pathologic Complete Response [ Time Frame: 4 years ] [ Designated as safety issue: No ]
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.
Pathologic complete response
Complete list of historical versions of study NCT00499122 on ClinicalTrials.gov Archive Site
  • To Define the Safety Profiles of Preoperative Administration of NOV-002 in Combination With Doxorubicin, Cyclophosphamide Followed by Docetaxel. [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
  • To Correlate Serum Protein Glutathionylation With Clinical and Pathologic Responses [ Time Frame: 4 years ] [ Designated as safety issue: No ]
Not Provided
Not Provided
Not Provided
 
Oxidized Glutathione (NOV-002), Doxorubicin, Cyclophosphamide, and Docetaxel in Treating Women With Newly Diagnosed Stage IIB, or Stage IIIC Breast Cancer
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

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.

OBJECTIVES:

Primary

  • 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.

Secondary

  • 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 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.

Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Breast Cancer
  • Drug: Cyclophosphamide
  • Drug: Docetaxel
  • Drug: Doxorubicin hydrochloride
  • Drug: Glutathione disulfide NOV-002
  • Procedure: conventional surgery
Experimental: NOV-002 and Doxorubicin, Cyclophosphamide and Docetaxel
Interventions:
  • Drug: Cyclophosphamide
  • Drug: Docetaxel
  • Drug: Doxorubicin hydrochloride
  • Drug: Glutathione disulfide NOV-002
  • Procedure: conventional surgery
Montero AJ, Diaz-Montero CM, Deutsch YE, Hurley J, Koniaris LG, Rumboldt T, Yasir S, Jorda M, Garret-Mayer E, Avisar E, Slingerland J, Silva O, Welsh C, Schuhwerk K, Seo P, Pegram MD, Glück S. Phase 2 study of neoadjuvant treatment with NOV-002 in combination with doxorubicin and cyclophosphamide followed by docetaxel in patients with HER-2 negative clinical stage II-IIIc breast cancer. Breast Cancer Res Treat. 2012 Feb;132(1):215-23. doi: 10.1007/s10549-011-1889-0. Epub 2011 Dec 3.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
41
April 2011
April 2011   (final data collection date for primary outcome measure)

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

  • 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

PRIOR CONCURRENT THERAPY:

  • 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 treatment
Female
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00499122
UMIAMI-20071167, MUSC-101072, MUSC-HR-17111
Yes
University of Miami Sylvester Comprehensive Cancer Center
University of Miami Sylvester Comprehensive Cancer Center
Not Provided
Study Chair: Keisuke Shirai, MD Medical University of South Carolina
Principal Investigator: Alberto Montero, MD University of Miami Sylvester Comprehensive Cancer Center
University of Miami Sylvester Comprehensive Cancer Center
August 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP