A Study of NK012 in Patients With Advanced, Metastatic Triple Negative Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00951054
Recruitment Status : Completed
First Posted : August 4, 2009
Last Update Posted : February 16, 2015
Information provided by (Responsible Party):
Nippon Kayaku Co.,Ltd.

May 21, 2009
August 4, 2009
February 16, 2015
February 2009
December 2014   (Final data collection date for primary outcome measure)
Antitumor activity (overall response rate) of NK012 [ Time Frame: At baseline and after every 2 cycles; PR or CR must be confirmed no less than 4 weeks after the first response was recorded ]
Same as current
Complete list of historical versions of study NCT00951054 on Archive Site
  • Duration of response [ Time Frame: Monthly for 6 months after patient goes off study, then every 3 months thereafter ]
  • Rate and duration of disease control [ Time Frame: Monthly for 6 months after patient goes off study, then every 3 months thereafter ]
  • Time to disease progression [ Time Frame: Monthly for 6 months after patient goes off study, then every 3 months thereafter ]
  • Toxicity profile of NK012 [ Time Frame: Duration of study, and up to 30 days after discontinuation ]
Same as current
Not Provided
Not Provided
A Study of NK012 in Patients With Advanced, Metastatic Triple Negative Breast Cancer
A Phase II Study of NK012 in Locally Advanced Non-Resectable and Metastatic Breast Cancer Patients With Triple Negative Phenotype
The purpose of this study is to determine whether NK012 is safe and effective in the treatment of advanced and metastatic triple negative breast cancer.
This is a Phase II, open label, single arm, multicenter study of NK012 in patients with locally advanced non-resectable and metastatic breast cancer with ER-negative, PR negative and HER2-negative phenotype. NK012 will be administered by infusion over 30 minutes once every 28 days (on Day 1 of each cycle). Patients will be screened for UGT1A1 polymorphism prior to enrollment in order to determine their starting dose.
Phase 2
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Triple Negative Breast Cancer
Drug: NK012
30 minute IV infusion once every 28 days. NK012 dose is 28 mg/m^2 (or 18 mg/m^2 depending on UGT1A1 polymorphism, with potential to dose escalate). Dose escalation cannot exceed 28 mg/m^2. Dosing will proceed until progression or unacceptable toxicity develops, or decision by patient or investigator to stop.
Not Provided
Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Same as current
February 2015
December 2014   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Histologically or cytologically confirmed diagnosis of breast cancer with locally advanced disease for which there is no surgical option, or stage IV disease.
  • ER-negative and PR-negative (defined as less than or equal to 10% tumor staining).
  • HER2-negative defined as one of the following:

    1. 0 or 1+ IHC;
    2. 2+ or 3+ IHC and FISH negative (ratio < 2.2);
    3. or FISH negative (ratio < 2.2).
  • No less than one and no more than two prior chemotherapy regimens for advanced or metastatic disease.
  • Prior chemotherapy must have included a taxane either as part of an adjuvant regimen or as part of a metastatic disease regimen.
  • Interval from last dose of prior treatment to enrollment in this study must be at least 4 weeks for cytotoxic chemotherapy (exception: 6 weeks for nitrosoureas or mitomycin C), 5 half-lives for non-cytotoxic therapy (to be reviewed by the Medical Monitor to establish start date), and 4 weeks for monoclonal antibodies; patients must have recovered from all acute toxicities.
  • Measurable disease by RECIST.
  • ECOG performance status of 0-2.
  • Females at least 18 years of age.
  • Adequate bone marrow function as defined by absolute neutrophil count of greater than or equal to 1,500/ mm^3 and platelets of greater than or equal to 100,000/mm^3.
  • AST(SGOT) and ALT(SGPT) levels no greater than 3 x the institutional ULN, and total bilirubin less than or equal to 1.5 x ULN.
  • Serum creatinine less than or equal to 1.5 x ULN, or creatinine clearance greater than or equal to 60 mL/min (Cockcroft-Gault formula) for patients with serum creatinine levels > 1.5 x ULN.
  • Able to understand and show willingness to sign a written informed consent document.

Exclusion criteria:

  • Patient has Gilbert's Syndrome.
  • Concurrent use of other investigational agent.
  • History of brain metastases or spinal cord compression, unless irradiated a minimum of 4 weeks before study entry and stable without requirement for corticosteroids for > 1 week.
  • Prior exposure to topoisomerase 1 inhibitors (i.e., irinotecan, topotecan, camptothecin).
  • Concurrent serious infections requiring parenteral therapy.
  • Pregnant or of childbearing potential and not using methods to avoid pregnancy. A negative pregnancy test (urine or serum) must be documented at baseline for women of childbearing potential. Patients may not breast-feed infants while on this study.
  • Significant cardiac disease including heart failure that meets New York Heart Association (NYHA) class III and IV definitions, history of myocardial infarction within one year of study entry, uncontrolled dysrhythmias or poorly controlled angina.
  • History of serious ventricular arrhythmia (VT or VF, greater than or equal to 3 beats in a row), QTc greater than or equal to 450 msec for men and 470 msec for women, or LVEF less than or equal to 40% by MUGA or ECHO.
Sexes Eligible for Study: Female
18 Years and older   (Adult, Older Adult)
Contact information is only displayed when the study is recruiting subjects
United States
Not Provided
Not Provided
Nippon Kayaku Co.,Ltd.
Nippon Kayaku Co.,Ltd.
Not Provided
Principal Investigator: Denise A Yardley, MD SCRI Development Innovations, LLC
Nippon Kayaku Co.,Ltd.
February 2015

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