Study Of Eribulin (E7389) In Patients With Advanced Solid Tumors And Normal Or Reduced Hepatic Function As Per Child-Pugh System

NCT ID: NCT00706095

Last Updated: 2012-03-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-02-29
• Study Completion Date: 2010-04-30

Brief Summary

This is an open-label, three-parallel group pharmacokinetic study. Patients with advanced solid tumors will be assigned to one of three groups to receive I.V. doses of eribulin (E7389). The three groups are: normal hepatic function, mild hepatic impairment (Child-Pugh A) and moderate hepatic impairment (Child-Pugh B) according to the Child-Pugh System for classifying hepatic impairment.

Conditions

Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

E7389 1.4 mg/m^2

Group Type: EXPERIMENTAL

E7389

Intervention Type: DRUG

E7389 Intravenous injection starting dose on Day 1 is 1.4 mg/m\^2 for normal hepatic function.

E7389 1.1 mg/m^2

Group Type: EXPERIMENTAL

E7389

Intervention Type: DRUG

E7389 Intravenous injection starting dose on Day 1 is 1.1 mg/m\^2 for mild hepatic impairment (Child-Pugh A)

E7839 0.7 mg/m^2

Group Type: EXPERIMENTAL

E7389

Intervention Type: DRUG

E7389 Intravenous injection starting dose on Day 1 is 0.7 mg/m\^2 for moderate hepatic impairment (Child-Pugh B)

Interventions

E7389

E7389 Intravenous injection starting dose on Day 1 is 1.4 mg/m\^2 for normal hepatic function.

Intervention Type: DRUG

E7389

E7389 Intravenous injection starting dose on Day 1 is 1.1 mg/m\^2 for mild hepatic impairment (Child-Pugh A)

Intervention Type: DRUG

E7389

E7389 Intravenous injection starting dose on Day 1 is 0.7 mg/m\^2 for moderate hepatic impairment (Child-Pugh B)

Intervention Type: DRUG

Other Intervention Names

Eribulin mesylate; Eribulin mesylate; Eribulin mesylate

Eligibility Criteria

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. 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 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 10^9/L, hemoglobin ≥ 10.0 g/dL (a hemoglobin <10.0 g/dL is acceptable if it is corrected by growth factor or transfusion), and platelet count ≥ 100 x 10^9/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.

• Mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic dysfunction 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

1. Patients who have received any of the following treatments within the specified period before E7389 treatment start:

1. Chemotherapy, radiation, biological therapy within 3 weeks.

2. Hormonal therapy within 1 week.

3. 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. Clinically significant drugs are listed in a comprehensive list that can be found at http://medicine/iupui.edu/flockhart/table.htm.

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 > New York Heart Association [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 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 > Grade 2.

18. Patients with other significant disease or disorders that, in the Investigator's opinion, would exclude the patient from the study.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eisai Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Prof. JHM Schellens

Role: PRINCIPAL_INVESTIGATOR

National Cancer Institute-Antoni van Leuwenhoek Hospital

Locations

Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital

Amsterdam, , Netherlands

Utrecht Medical Centre

Utrecht, , Netherlands

Countries

Netherlands

Other Identifiers

E7389-E044-108

Identifier Type: -

Identifier Source: org_study_id