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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Nippon Kayaku Co.,Ltd.
ClinicalTrials.gov Identifier:
NCT00951054
First received: May 21, 2009
Last updated: March 18, 2013
Last verified: March 2013
  Purpose

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.


Condition Intervention Phase
Triple Negative Breast Cancer
Drug: NK012
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of NK012 in Locally Advanced Non-Resectable and Metastatic Breast Cancer Patients With Triple Negative Phenotype

Resource links provided by NLM:


Further study details as provided by Nippon Kayaku Co.,Ltd.:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Duration of response [ Time Frame: Monthly for 6 months after patient goes off study, then every 3 months thereafter ] [ Designated as safety issue: No ]
  • Rate and duration of disease control [ Time Frame: Monthly for 6 months after patient goes off study, then every 3 months thereafter ] [ Designated as safety issue: No ]
  • Time to disease progression [ Time Frame: Monthly for 6 months after patient goes off study, then every 3 months thereafter ] [ Designated as safety issue: No ]
  • Toxicity profile of NK012 [ Time Frame: Duration of study, and up to 30 days after discontinuation ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 61
Study Start Date: February 2009
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Intervention Details:
    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.
Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00951054

Locations
United States, Tennessee
Sarah Cannon Research Institute
Nashville, Tennessee, United States, 37203
Sponsors and Collaborators
Nippon Kayaku Co.,Ltd.
Investigators
Principal Investigator: Denise A Yardley, MD SCRI Development Innovations, LLC
  More Information

No publications provided

Responsible Party: Nippon Kayaku Co.,Ltd.
ClinicalTrials.gov Identifier: NCT00951054     History of Changes
Other Study ID Numbers: A6012211US
Study First Received: May 21, 2009
Last Updated: March 18, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Nippon Kayaku Co.,Ltd.:
breast cancer
triple negative
ER-negative
PR-negative
HER2-negative
ER-, PR-, HER2- (Triple Negative) breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases

ClinicalTrials.gov processed this record on July 23, 2014