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

NCT00499122 | Completed Phase 2 Results DMC

• 3 other identifiers: 20071167MUSC-101072MUSC-HR-17111
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Breast Cancer

Keywords

stage II breast cancer; stage IIIC breast cancer; inflammatory breast cancer

Outcome Measures

Primary Outcomes (1)

• Rate of Pathologic Complete Response in the Affected Breast After Protocol Therapy

  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. 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.

  About 7 months

Secondary Outcomes (2)

• Definition of the Safety Profiles of Protocol Therapy

  Up to 30 days Post-Last Dose of Protocol Therapy, About 7 months

• Correlation Between Myeloid Derived Suppressor Cell (MDSC) Levels and Pathologic Complete Response (pCR) and Non-Responders

  Baseline, Day 1 of Cycles 1 through 8, about 7 months

Study Arms (1)

NOV-002 and Chemotherapy

EXPERIMENTAL

* NOV-002: * Cycle 1, Day -1 only: 60 mg intravenously (IV) x 2, 3 hours (+/- 30 minutes) apart * Cycles 1 - 8, Day 1: 60 mg IV, 1 hour (+/- 30 minutes) prior to chemotherapy administration * Cycle 1 - 8, Days 2 - 21: 60 mg subcutaneous injections * Cyclophosphamide: 600 mg/m2 IV, Cycles 1 - 4, Day 1 * Doxorubicin: 60 mg/m2 IV, Cycles 1 - 4, Day 1 * Docetaxel: 100 mg/m2 IV, Cycles 5 - 8, Day 1

Drug: Cyclophosphamide; Drug: Docetaxel; Drug: Doxorubicin; Drug: NOV 002

Interventions

Cyclophosphamide DRUG

Also known as: Cytoxan

NOV-002 and Chemotherapy

Docetaxel DRUG

Also known as: Cytoxan

NOV-002 and Chemotherapy

Doxorubicin DRUG

Also known as: Adriamycin

NOV-002 and Chemotherapy

NOV 002 DRUG

Also known as: Oxidized glutathione

NOV-002 and Chemotherapy

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• University of Miami: lead

Study Sites (2)

University of Miami

Miami, Florida, 33136, United States

Location

Hollings Cancer Center at Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Related Publications (1)

• 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, Gluck 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.

  PMID: 22138748 RESULT

MeSH Terms

Conditions

Breast Neoplasms; Inflammatory Breast Neoplasms

Interventions

Cyclophosphamide; Docetaxel; Doxorubicin; NOV 002; Glutathione Disulfide

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Diterpenes; Terpenes; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Glutathione; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Alberto Montero MD
• Organization: UM/Sylvester Comprehensive Cancer Center

amontero2@med.miami.edu

305-243-3771

Study Officials

• Keisuke Shirai, MD

  Medical University of South Carolina

  STUDY CHAIR

• Alberto Montero, MD

  University of Miami

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 10, 2007
• First Posted: July 11, 2007
• Study Start: June 4, 2007
• Primary Completion: April 1, 2011
• Study Completion: April 1, 2011
• Last Updated: January 2, 2018
• Results First Posted: March 29, 2013

Record last verified: 2017-12

Locations

US (2)