Study of NK012 and Carboplatin in Solid Tumors With Dose Expansion in Triple Negative Breast Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Nippon Kayaku Co.,Ltd.
ClinicalTrials.gov Identifier:
NCT01238952
First received: November 2, 2010
Last updated: March 18, 2013
Last verified: March 2013
  Purpose

The primary objective is to determine the maximum tolerated dose/recommended phase II dose of the combination regimen of NK012 and carboplatin in patients with advanced solid tumors.


Condition Intervention Phase
Advanced Solid Tumors
Metastatic Triple Negative Breast Cancer
Drug: NK012 and carboplatin
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of NK012 in Combination With Carboplatin in Patients With Advanced Solid Tumors Followed by a Dose Expansion Phase in Patients With Triple Negative Metastatic Breast Cancer

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Number of patients with dose-limiting toxicity as determinant of the maximum tolerated dose/recommended dose [ Time Frame: From date of first dose to off-study (or 30 days since last dose) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Number of patients with adverse events as a measure of safety and tolerability [ Time Frame: From date of first dose to off-study (or 30 days since last dose) ] [ Designated as safety issue: Yes ]
  • Tumor measurements, as a measure of efficacy [ Time Frame: Baseline, then on average every 2 months until off-study ] [ Designated as safety issue: No ]
    Efficacy, based on RECIST 1.1, will be assessed in all solid tumors, and in a specific subset of patients with breast cancer

  • Peak Plasma Concentration (Cmax) of NK012 and carboplatin [ Time Frame: 15,30,60min,1,6,24,48,50,72hrs,1,2,3,4wk ] [ Designated as safety issue: No ]
  • Area under the plasma concentration versus time curve (AUC) of NK012 and carboplatin [ Time Frame: 15,30,60min,1,6,24,48,50,72hrs,1,2,3,4wk ] [ Designated as safety issue: No ]

Enrollment: 4
Study Start Date: July 2010
Study Completion Date: March 2013
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: NK012 and carboplatin
    NK012 and carboplatin via infusion once every 28 days
Detailed Description:

NK012 will be administered as a 30 minute IV infusion, followed by a 30 minute carboplatin IV infusion. Both drugs will be administered once every 28 days. Treatment is expected to continue for 6 cycles, unless disease progression or the development of unacceptable toxicity requires discontinuation of the drug. At the discretion of the investigator, patients who show signs of benefit may continue beyond 6 cycles.

Once a MTD/RD has been determined, a dose expansion cohort of patients with metastatic triple negative breast cancer will be treated at the determined MTD.

  Eligibility

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

Inclusion Criteria:

  1. Histologically or cytologically confirmed diagnosis of advanced solid tumor for which no efficacious therapy exists, or for which a camptothecin-based regimen would be appropriate.
  2. For the dose expansion at the MTD/RD only:

    1. Patients must have triple-negative breast cancer with locally advanced disease for which there is no surgical option, or stage IV disease. Triple-negative breast cancer is defined as HER2-negative, ER-negative, and PR-negative as follows:

      For HER2- negative (must meet one of the following 3):

      ( i) FISH negative (ratio <2.2); or ( ii) IHC 0 or 1+; or (iii) IHC 2+ or 3+ and FISH negative (ratio <2.2) For ER negative and PR negative: ≤ 10% tumor staining by IHC

    2. No less than one and no more than two prior chemotherapy regimens for advanced or metastatic breast cancer.
    3. Patients must have measurable disease by RECIST (version 1.1).
  3. Patients must have recovered from all acute adverse effects of prior therapies, excluding alopecia.
  4. For patients enrolled in the dose escalation phase, no more than 4 prior cytotoxic regimens in the metastatic setting.
  5. Prior irradiation to no more than 25% of the bone marrow.
  6. ECOG performance status of 0 or 1.
  7. Life expectancy of at least 12 weeks.
  8. Patients are at least 18 years of age.
  9. Adequate bone marrow function defined as ANC ≥ 1500/mm^3 and platelet count ≥ 100,000/mm^3.
  10. AST and ALT ≤ 3.0 x ULN (5X ULN if documented liver metastases) and total bilirubin ≤ 1.5 x ULN.
  11. Serum creatinine < 1.5 x ULN, or creatinine clearance > 60 mL/min by Cockcroft-Gault formula* for patients with serum creatinine > 1.5x ULN.

    * Cockcroft-Gault formula for creatinine clearance (CrCl): Males: CrCl (ml/min) = (140 - age) x wt (kg) / (serum creatinine x 72) Females: Multiply the above result by 0.85

  12. Able to understand and show willingness to sign a written informed consent document.

Exclusion Criteria:

  1. Prior chemotherapy, radiation therapy, or investigational therapy within 4 weeks (exception: 6 weeks for nitrosoureas or mitomycin C); or prior non-cytotoxic therapy within 5 drug half-lives (or 4 weeks, which ever is shorter); or monoclonal antibodies within 4 weeks prior to the first dose of study treatment.
  2. Concurrent use of another investigational agent.
  3. History of brain metastases or spinal cord compression, unless irradiated or treated a minimum of 4 weeks prior to first study treatment and stable without requirement of corticosteroids for > 1 week.
  4. Concurrent serious infections requiring parenteral antibiotic therapy.
  5. Pregnant or of childbearing potential and not using methods to avoid pregnancy. A negative pregnancy test must be documented at baseline for women of child-bearing potential. Patients may not breast feed infants while on this study.
  6. Significant cardiac disease including heart failure that meets NYHA class III and IV definitions, history of myocardial infarction within 6 months of study entry, uncontrolled dysrhythmias or poorly controlled angina.
  7. History of serious ventricular arrhythmia (VT or VF, ≥ 3 beats in a row), QTc ≥ 450 msec for men and 470 msec for women, or LVEF ≤ 40% by MUGA or ECHO.
  8. History of allergic reactions attributed to compounds of topoisomerase I inhibitors, or platinum-containing compounds.
  9. Prior treatment with irinotecan.
  10. Prior treatment with more than 6 cycles of platinum drugs.
  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: NCT01238952

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

No publications provided

Responsible Party: Nippon Kayaku Co.,Ltd.
ClinicalTrials.gov Identifier: NCT01238952     History of Changes
Other Study ID Numbers: A6012121US
Study First Received: November 2, 2010
Last Updated: March 18, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Nippon Kayaku Co.,Ltd.:
solid tumors
breast cancer
triple negative breast cancer
HER2 negative
ER negative
PR negative

Additional relevant MeSH terms:
Neoplasms
Breast Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Carboplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 29, 2014