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A Phase II Study of NK012 in Locally Advanced Non-Resectable and Metastatic Breast Cancer Patients With Triple Negative Phenotype

Phase 2
18 Years
Open (Enrolling)
Triple Negative Breast Cancer

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Trial Information

A Phase II Study of NK012 in Locally Advanced Non-Resectable and Metastatic Breast Cancer Patients With Triple Negative Phenotype

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.

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,

- 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

- 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.

Type of Study:


Study Design:

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

Outcome Measure:

Antitumor activity (overall response rate) of NK012

Outcome 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

Safety Issue:


Principal Investigator

Denise A Yardley, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Sarah Cannon Research Institute


United States: Food and Drug Administration

Study ID:




Start Date:

February 2009

Completion Date:

December 2014

Related Keywords:

  • Triple Negative Breast Cancer
  • breast cancer
  • triple negative
  • ER-negative
  • PR-negative
  • HER2-negative
  • ER-, PR-, HER2- (Triple Negative) breast cancer
  • Breast Neoplasms



Sarah Cannon Research InstituteNashville, Tennessee  37203