Cancer Drug metabolism
Conditions
Interventions
All three groups will receive on day 1 and day 8 of the 21 day cycle Eribulin
intravenously as bolusinjection of infusion diluted in 100 ml NaCl 0,9% in 2-5
minutes.
Sponsors
Eisai
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
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 = 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 = 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)
Exclusion 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Exploratory analyses of the influence of hepatic impairment on plasma pharmacokinetics of eribulin mesylate (E7389) administered as intravenously. Comparisons will be made between the single doses of eribulin mesylate (E7389) administered to the three groups of patients | — |
Secondary
| Measure | Time frame |
|---|---|
| Further exploration of safety and tolerability of eribulin mesylate (E7389) among patients with reduced hepatic function | — |
Countries
Netherlands
Outcome results
None listed