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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

Phase 1
18 Years
Not Enrolling

Thank you

Trial Information

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

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

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

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.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Outcome Time Frame:

28 days

Safety Issue:


Principal Investigator

Jantien Wanders, M.D.

Investigator Role:

Study Director

Investigator Affiliation:

Eisai Limited


The Netherlands: Centrale Commissie Mensgebonden Onderzoek (CCMO)

Study ID:




Start Date:

February 2009

Completion Date:

September 2009

Related Keywords:

  • Cancer
  • Cancer
  • solid tumors