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

NCT00706095 | Completed Phase 1 Results

• 1 other identifier: E7389-E044-108
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

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

Keywords

Cancer; advanced solid tumors

Outcome Measures

Primary Outcomes (3)

• Mean (SD) Pharmacokinetic (PK) Parameter Area Under Concentration Time Curve From Zero to Infinity (AUC0-oo)

  Pre-dose (-0.5h); post-dose at 15 min, 30 min, 60 min, 2 hrs, 4 hrs, 6 hrs, 10 hrs, 24 hrs, 48 hrs, 72hrs, 96 hrs, 120 hrs and 144 hours.

• Mean (SD) Pharmacokinetic (PK) Parameter Maximum Observed Plasma Concentration (Cmax)

  Pre-dose (-0.5h); post-dose at 15 min, 30 min, 60 min, 2 hrs, 4 hrs, 6 hrs, 10 hrs, 24 hrs, 48 hrs, 72hrs, 96 hrs, 120 hrs and 144 hours.

• Best Overall Response Per Response Evaluation Criteria in Solid Tumors (RECIST)

  Defined as the best response from the start of treatment until disease progression or recurrence. Lesions measured by computed tomography (CT) scan and magnetic resonance imaging (MRI). Objective response rate: complete response (CR-disappearance of all lesions)+ partial response (PR-30% decrease in lesion diameter), Progressive Disease (PD-20% increase in lesion diameter), stable disease (SD-neither shrinkage nor increase of lesions).

  throughout the study and up to 30 days after the last dose of study drug

Study Arms (3)

E7389 1.4 mg/m^2

EXPERIMENTAL

Drug: E7389

E7389 1.1 mg/m^2

EXPERIMENTAL

Drug: E7389

E7839 0.7 mg/m^2

EXPERIMENTAL

Drug: E7389

Interventions

E7389 DRUG

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

Also known as: Eribulin mesylate

E7389 1.4 mg/m^2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• Age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2.
• Life expectancy of ≥ 3 months
• 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.
• 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
• Patients willing and able to comply with the study protocol for the duration of the study
• 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

You may not qualify if:

• Patients who have received any of the following treatments within the specified period before E7389 treatment start:
• Chemotherapy, radiation, biological therapy within 3 weeks.
• Hormonal therapy within 1 week.
• Any investigational drug within 4 weeks.
• Patients with any clinically significant laboratory abnormality except for those parameters influenced by hepatic impairment.
• Patients with severe (Child-Pugh C) hepatic dysfunction according to the Child-Pugh scoring system.
• Patients with encephalopathy ≥ Grade 1.
• 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.
• 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.
• 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.
• Fertile men who are not willing to use contraception or fertile men with a female partner who are not willing to use contraception
• Severe/uncontrolled intercurrent illness/infection.
• 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).
• Patients with organ allografts requiring immunosuppression (not including blood and blood components transfusions).
• Patients with known positive HIV status.

Sponsors & Collaborators

• Eisai Inc.: lead

Study Sites (2)

Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital

Amsterdam, 1066 CX, Netherlands

Location

Utrecht Medical Centre

Utrecht, Netherlands

Location

MeSH Terms

Conditions

Neoplasms

Interventions

eribulin

Results Point of Contact

• Title: Eisai Inc.
• Organization: Eisai Call Center

888-422-4743

Study Officials

• Prof. JHM Schellens

  National Cancer Institute-Antoni van Leuwenhoek Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 4, 2008
• First Posted: June 27, 2008
• Study Start: February 1, 2008
• Primary Completion: September 1, 2009
• Study Completion: April 1, 2010
• Last Updated: March 27, 2012
• Results First Posted: January 30, 2012

Record last verified: 2012-03

Locations

NL (2)