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Evaluating the Pharmacokinetics and Tolerance of Co-administration of Oral Multiple Dose of Ketoconazole and an IV (Bolus) Infusion of Eribulin in Patients With Advanced Solid Tumors

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ClinicalTrials.gov Identifier: NCT01000376
Recruitment Status : Completed
First Posted : October 23, 2009
Results First Posted : September 23, 2013
Last Update Posted : September 23, 2013
Sponsor:
Information provided by (Responsible Party):
Eisai Inc. ( Eisai Limited )

Tracking Information
First Submitted Date  ICMJE October 22, 2009
First Posted Date  ICMJE October 23, 2009
Results First Submitted Date  ICMJE December 22, 2011
Results First Posted Date  ICMJE September 23, 2013
Last Update Posted Date September 23, 2013
Study Start Date  ICMJE February 2009
Actual Primary Completion Date August 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 19, 2013)
  • Mean (SD) Maximum Observed Concentration (Cmax) of Eribulin [ Time Frame: 7 days after dosing on Days 1 and 15 ]
  • Mean (SD) Area Under Concentration Time Curve From Zero to Infinity (AUC 0-oo) of Eribulin [ Time Frame: 7 days after dosing on Days 1 and 15 ]
Original Primary Outcome Measures  ICMJE
 (submitted: October 22, 2009)
PK sampling days 1 to 7 and 15 to 21 in Cycle 1 only. An extra predose blood sample to predict cytochrome P450 (CYP) 3A4 and (CYP) 3A5 phenotype [ Time Frame: 28 days ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 19, 2013)
Safety of Eribulin Administered Alone or Coadministered With Oral Ketoconazole, as Measured by Number of Subjects With Adverse Events. [ Time Frame: monitored throughout ]
Original Secondary Outcome Measures  ICMJE
 (submitted: October 22, 2009)
Safety and tolerability of eribulin co-administered with oral ketoconazole. Safety and tolerability of eribulin given alone on Days 1 and 8 of a 21-day schedule. [ Time Frame: monitored throughout ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Evaluating the Pharmacokinetics and Tolerance of Co-administration of Oral Multiple Dose of Ketoconazole and an IV (Bolus) Infusion of Eribulin in Patients With Advanced Solid Tumors
Official Title  ICMJE An Open-Label, Phase I Study to Evaluate the Pharmacokinetics and Tolerance of Co-administration of Oral Multiple Dose of Ketoconazole and an IV (Bolus) Infusion of Eribulin in Patients With Advanced Solid Tumors
Brief Summary The purpose of this study is to investigate whether ketoconazole, taken orally, influences the level of eribulin in the blood when the two drugs are given at the same time. The study will enroll patients with solid tumors whose cancer became worse even after standard treatment, or for whom there is no standard treatment available. The study will also investigate whether eribulin given together with ketoconazole is safe (has few side-effects) and is effective against cancer.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Cancer
Intervention  ICMJE
  • Drug: Eribulin alone
    Group 1 Cycle 1 (28 days): Eribulin IV 1.4 mg/m^2 alone on Day 1, then eribulin IV 0.7 mg/m^2 plus oral ketoconazole 200 mg on Day 15 and oral ketoconazole 200 mg alone on Day 16. Subsequently, subjects were able to receive eribulin 1.4 mg/m^2 on Days 1 and 8 every 21 days.
  • Drug: Eribulin plus Ketoconazole
    Group 2 Cycle 1 (28 days): Eribulin IV 0.7 mg/m^2 plus oral ketoconazole 200 mg on Day 1, then oral ketoconazole 200 mg alone on Day 2 and eribulin IV 1.4 mg/m^2 alone on Day 15. Subsequently, subjects were able to receive eribulin 1.4 mg/m^2 on Days 1 and 8 every 21 days.
Study Arms  ICMJE
  • Experimental: Group 1
    Intervention: Drug: Eribulin alone
  • Experimental: Group 2
    Intervention: Drug: Eribulin plus Ketoconazole
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 22, 2009)
12
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE September 2009
Actual Primary Completion Date August 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Patients must have a histologically or cytologically confirmed advanced solid tumor that has progressed following standard therapy or for which no standard therapy exists (including surgery or radiation therapy).
  2. Resolution of all chemotherapy or radiation-related toxicities to Grade 1 severity or lower, except for stable sensory neuropathy ≤ Grade 2 and alopecia.
  3. Patients must be aged ≥ 18 years.
  4. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
  5. Life expectancy of ≥ 3 months.
  6. Patients must have adequate renal function as evidenced by serum creatinine ≤ 2.0 mg/dL (≤ 176 mol/L) or calculated creatinine clearance ≥ 40 mL/minute (min) per the Cockcroft and Gault formula.
  7. Patients must have adequate hepatic function as evidenced by bilirubin ≤ 1.5 times the upper limit of normal (ULN) and alkaline phosphatase, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) ≤ 3 times the ULN, (in the case of liver metastases ≤ 5 times ULN or in the case of bone metastases, the liver specific alkaline phosphatase ≤ 3 times ULN).
  8. Patients must have adequate bone marrow function as evidenced by absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L, hemoglobin ≥ 10.0 g/dL or ≥ 6.2 mmol/L (a hemoglobin < 10.0 g/dL or < 6.2 mmol/L is acceptable if it is corrected by growth factor or transfusion), and platelets ≥ 100 x 10^9/L.
  9. Patients must be willing and able to comply with the study protocol for the duration of the study.
  10. Patients must give written informed consent prior to any study-specific screening procedures with the understanding that the patient may withdraw consent at any time without prejudice.

Exclusion Criteria:

  1. Patients who have received any of the following treatments within the specified period before eribulin treatment starts:

    1. Chemotherapy, radiation or biological therapy within 2 weeks.
    2. Hormonal therapy within 1 week.
    3. Any investigational drug within 4 weeks.
  2. Patients who are receiving anti-coagulant therapy with warfarin or related compounds, other than for line patency and cannot be changed to heparin-based therapy, are not eligible. If a patient is to continue on mini-dose warfarin, then the prothrombin time (PT) or international normalized ratio (INR) must be closely monitored.
  3. Patients receiving, at the time the study starts, any medication, dietary supplements or other compounds or substances known to induce or inhibit CYP3A4 activity, with the exception of ketoconazole. A comprehensive list can be found at http://medicine/iupui.edu/flockhart/table.htm.
  4. Patients for whom the use of ketoconazole is contraindicated.
  5. Patients who are receiving drugs that might influence ketoconazole metabolism.
  6. Women who are pregnant or breast-feeding; women of childbearing potential with either a positive pregnancy test at screening or no pregnancy test; women of childbearing potential unless (1) surgically sterile or (2) using adequate measures of contraception in the opinion of the Investigator. Perimenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential.
  7. Fertile men who are not willing to use contraception or fertile men with a female partner who is not willing to use contraception.
  8. Patients whose intestinal absorption is impaired.
  9. Severe/uncontrolled intercurrent illness/infection.
  10. Significant cardiovascular impairment (history of congestive heart failure > New York Heart Association (NYHA) Grade II, unstable angina or myocardial infarction within the past 6 months, or serious cardiac arrhythmia.
  11. Patients with organ allografts requiring immunosuppression (not including blood and blood components transfusions).
  12. Patients with known positive human immunodeficiency virus (HIV) status.
  13. Patients with brain or subdural metastases are not eligible, unless they have completed local therapy and have discontinued the use of corticosteroids for this indication for at least 4 weeks before starting treatment with eribulin.
  14. Patients with meningeal carcinomatosis.
  15. Patients with a hypersensitivity to halichondrin B and/or halichondrin B-like compounds.
  16. Patients with pre-existing neuropathy > Grade 2.
  17. Patients with other significant disease or disorders that, in the Investigator's opinion, would exclude the patient from the study.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Netherlands
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01000376
Other Study ID Numbers  ICMJE E7389-E044-109
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Eisai Inc. ( Eisai Limited )
Study Sponsor  ICMJE Eisai Limited
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Jantien Wanders, M.D. Eisai Limited
PRS Account Eisai Inc.
Verification Date September 2013

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