An Open-Label Study to Assess the Pharmacokinetics and Safety of HALAVEN in Subjects With Cancer Who Also Have Impaired Renal Function

Phase 1

Completed

• Conditions: Unspecified Adult Solid Tumor, Protocol Specific
• Interventions: Drug: E7389

• Registration Number: NCT01418677
• Lead Sponsor: Eisai Inc.

Brief Summary

This is an open-label non-randomized study in subjects with advanced or metastatic solid tumors who are no longer responding to available therapy. HALAVEN will be administered to subjects on Days 1 and 8 of a 21-day cycle.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2011-08-01
• Study First Submitted QC: 2011-08-16
• Study First Posted: 2011-08-17
• Study Start: 2011-10
• Primary Completion: 2014-07
• Study Completion: 2015-05
• Status Verified: 2016-05
• Last Update Submitted: 2016-05-13
• Last Update Posted: 2016-05-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 19

Inclusion Criteria

• Histologically or cytologically confirmed advanced solid tumors that have progressed following standard therapy or for which no standard therapy exists (including surgery or radiation therapy).
• Renal function must fall into one of the following categories:
• Normal function - creatinine clearance greater than or equal to 80 mL/min.
• Moderate impairment - creatinine clearance >30 to 50 mL/min.
• Severe impairment - creatinine clearance 15 to less than 30 mL/min.
• Adequate liver function as evidenced by bilirubin less than or equal to 1.5 times the upper limit of normal (ULN) and alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) less than or equal to 3 times the ULN (in the case of liver metastasis less than or equal to 5 times ULN). In the case ALP >3 times the ULN (in the absence of liver metastasis) or >5 times the ULN (in the presence of liver metastasis), and the subject is also known to have bone metastasis, the liver specific ALP must be separated from the total and used to assess the liver function instead of the total ALP.

Exclusion Criteria

• Subjects with mild renal impairment (creatinine clearance greater than 50 to less than 80 mL/min).
• Subjects with end stage renal disease (creatinine clearance less than 15 mL/min or on dialysis).
• Subjects with a hypersensitivity to halichondrin B and/or halichondrin B chemical derivatives.
• Subjects with prior participation in an HALAVEN clinical study, even if not previously assigned to HALAVEN treatment.
• Radiation therapy encompassing >30 % of bone marrow.
• Subjects with organ allografts requiring immunosuppression.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Cohort 1	E7389	-
Cohort 3	E7389	-
Cohort 2	E7389	-

Primary Outcome Measures

Name	Time	Method
To study the influence of moderate and severe renal impairment on the Composite of Pharmacokinetics of HALAVEN following a single intravenous administration to subjects with cancer.	Halaven will be measured on Day 1 and 8 of a 21 day cycle.	The primary analysis will be conducted using the dose-normalized primary PK parameters (AUC0-inf, AUC0-last, and Cmax) respectively. Relationships between each individual PK parameter and renal function (creatinine clearance) will be analyzed by linear regression models using the PK parameter as the dependent variable and renal function as the independent variable.

Secondary Outcome Measures

Name	Time	Method
Number of Participants with Adverse Events as a Measure of Safety and Tolerability of HALAVEN in subjects with moderate or severe renal impairment, as well as in those with normal renal function.	Halaven will be measured on Day 1 and 8 of a 21 day cycle.	Safety data that will be evaluated include adverse events, clinical laboratory results, physical examination results, ECG, and vital signs