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

Study Overview
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Brief Summary
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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.

Official Title
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An Open-Label Phase 1 Study to Assess the Pharmacokinetics and Safety of HALAVEN in Subjects With Cancer Who Also Have Impaired Renal Function

Conditions
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Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: E7389
* Drug: E7389
* Drug: E7389


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Cohort 1<br> | Drug: E7389<br>* Severe renal impairment-the dose to be administered will be based on the interim analyses of safety and pharmacokinetics in subjects with moderate renal impairment (Cohort 1).<br>* Other names: Halaven;|
| Active Comparator: Cohort 2<br> | Drug: E7389<br>* Moderate renal impairment-HALAVEN will be dosed at 1.4 mg/m2.<br>* Other names: Halaven;|
| Active Comparator: Cohort 3<br> | Drug: E7389<br>* Normal renal function-HALAVEN will be dosed at 1.4 mg/m2.<br>* Other names: Halaven;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | Halaven will be measured on Day 1 and 8 of a 21 day cycle. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Safety data that will be evaluated include adverse events, clinical laboratory results, physical examination results, ECG, and vital signs | Halaven will be measured on Day 1 and 8 of a 21 day cycle. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Unspecified Advance Solid Tumor, Protocol Specific