An open-label, parallel group study to explore the pharmacokinetics of eribulin (E7389) in patients with advanced solid tumors and normal or reduced hepatic function according to the Child Pugh system.

Conditions: Cancer
Drug metabolism
10027656

Registration Number: NL-OMON33939

Lead Sponsor: Eisai

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Pending

Sex: Not specified

Target Recruitment: 18

Inclusion Criteria

General Inclusion Criteria for all Groups
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. Age >= 18 years
3. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
4. Life expectancy of >= 3 months
5. Adequate renal function as evidenced by serum creatinine <= 2.0 mg/dL (176 µmol/L) or calculated creatinine clearance >= 40 mL/minute (min) per the Cockcroft and Gault formula
6. Adequate bone marrow function as evidenced by absolute neutrophil count (ANC) >= 1.5 x 109/L, hemoglobin >= 10.0 g/dL (>= 6.2 mmol/L) (a hemoglobin < 10.0 g/dL (< 6.2 mmol/L) is acceptable if it is corrected by growth factor or transfusion), and platelet count >= 100 x 109/L
7. Patients willing and able to comply with the study protocol for the duration of the study
8. Written informed consent prior to any study-specific screening procedures with the understanding that the patient may withdraw consent at any time without prejudice
Additional Inclusion Criteria for the Group of Patients with No Hepatic Impairment
Patients must meet all the general inclusion criteria listed above plus have:
Normal hepatic function as evidenced by: International Normalized Ratio (INR), albumin, bilirubin, alanine transaminase (ALT) and aspartate transaminase (AST) within the institution*s normal laboratory ranges and alkaline phosphatase (ALP) <= 2.5 times the upper limit of normal range (ULN) and with no clinical signs of ascites.
Additional Inclusion Criteria for the Group of Patients with a History of Known Hepatic Impairment
Patients must meet all the general inclusion criteria listed above plus have either:
Mild hepatic dysfunction (Child-Pugh A) according to the Child-Pugh scoring system criteria, where patients with laboratory values within normal ranges will not be included in the Child-Pugh A category
Or, Moderate hepatic dysfunction (Child-Pugh B) according to the Child-Pugh scoring system criteria

Exclusion Criteria

Exclusion Criteria
1. Patients who have received any of the following treatments within the specified period before eribulin mesylate (E7389) treatment start:
a Chemotherapy, radiation, biological therapy within 3 weeks
b Hormonal therapy within 1 week
c Any investigational drug within 4 weeks
2. Patients with any clinically significant laboratory abnormality except for those parameters influenced by hepatic impairment.
3. Patients with severe (Child-Pugh C) hepatic dysfunction according to the Child-Pugh scoring system
4. Patients with encephalopathy >= grade 1
5. Patients receiving any drug known to induce or inhibit CYP3A4 activity.
6. Patients, who require therapeutic anti-coagulant therapy other than for line patency with warfarin or related compounds and cannot be changed to heparin-based therapy, are not eligible
7. 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.
8. Fertile men who are not willing to use contraception or fertile men with a female partner who are not willing to use contraception
9. Severe/uncontrolled intercurrent illness/infection
10. Significant cardiovascular impairment (history of congestive heart failure > NYHA grade II, unstable angina or myocardial infarction within the past six months, or serious cardiac arrhythmia)
11. Patients with organ allografts requiring immunosuppression (not including blood and blood components transfusions)
12. Patients with known positive HIV status
13. Patients with brain or subdural metastases are not eligible, unless they are stable and have completed local therapy and have discontinued the use of corticosteroids for this indication for at least four weeks before starting treatment with eribulin mesylate (E7389).
14. Patients with meningeal carcinomatosis
15. Patients with a hypersensitivity to halichondrin B and/or halichondrin B-like compounds
16. Patients who participated in a prior E7389 clinical trial
17. Patients with preexisting neuropathy > G2
18. Patients with other significant disease or disorders that, in the Investigator*s opinion, would exclude the patient from the study

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Exploratory analyses of the influence of hepatic impairment on plasma<br /><br>pharmacokinetics of eribulin mesylate (E7389) administered as intravenously.<br /><br>Comparisons will be made between the single doses of eribulin mesylate (E7389)<br /><br>administered to the three groups of patients </p><br>

Secondary Outcome Measures