Exatecan Mesylate in Treating Patients With Advanced Solid Tumors and Kidney Dysfunction

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: Phase I trial to study the effectiveness of exatecan mesylate in treating patients who have advanced solid tumors and kidney dysfunction.

Detailed Description
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OBJECTIVES: Determine the maximum tolerated dose of exatecan mesylate in patients with advanced solid tumors and varying degrees of renal dysfunction. Determine the dose-limiting and non-dose-limiting toxic effects of this drug in these patients. Determine the effects of renal dysfunction on the plasma pharmacokinetics and pharmacodynamics of this drug in these patients. Establish a model for dosing this drug in patients with impaired renal function. OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to severity of renal dysfunction (normal vs mild vs moderate vs severe). Patients receive exatecan mesylate IV over 30 minutes on days 1-5. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients in each renal dysfunction stratum receive escalating doses of exatecan mesylate until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Patients in the normal renal function stratum do not undergo dose escalation. Patients are followed every 3 months. PROJECTED ACCRUAL: A total of 45 patients (6 normal, 9 mild, 12 moderate, and 18 severe renal dysfunction) will be accrued for this study within 1.5 years.

Official Title
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A Phase I Study of DX-8951f (Exatecan Mesylate for Injection) in Patients With Renal Dysfunction

Conditions
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Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: exatecan mesylate


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed advanced solid tumor refractory to standard therapy or for which no standard therapy exists Renal function as defined by the following parameters: Normal (creatinine clearance (CrCl) greater than 80 mL/min) Mild dysfunction (CrCl 50-80 mL/min) Moderate dysfunction (CrCl 30-50 mL/min) Severe dysfunction (CrCl less than 30 mL/min) End-stage renal disease (requiring dialysis) No symptomatic or active brain metastases (e.g., edema or progression on CT scan or MRI) PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-2 Life expectancy At least 12 weeks Hematopoietic Absolute neutrophil count at least 1,500/mm3 Platelet count at least 100,000/mm3 Hemoglobin at least 9.0 g/dL Hepatic Bilirubin normal AST or ALT no greater than 2 times upper limit of normal Albumin at least 2.8 g/dL Renal See Disease Characteristics Cardiovascular No active congestive heart failure No uncontrolled angina No myocardial infarction within the past 6 months Other No concurrent serious infection No other life-threatening illness No overt psychosis or mental disability or other incompetency that would preclude informed consent Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy No concurrent anticancer biologic therapy Chemotherapy At least 4 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosourea) and recovered No prior exatecan mesylate No other concurrent anticancer chemotherapy Endocrine therapy No concurrent anticancer hormonal therapy Concurrent megestrol for appetite stimulation allowed Radiotherapy At least 4 weeks since prior radiotherapy and recovered No concurrent anticancer radiotherapy Surgery At least 4 weeks since prior major surgery and recovered No concurrent anticancer surgery Other At least 4 weeks since prior investigational drugs including analgesics or antiemetics At least 1 week since prior grapefruit juice No other concurrent anticancer therapy No other investigational drugs during and for 4 weeks after study No concurrent grapefruit juice No other concurrent anticancer cytotoxic therapy Concurrent chronic hemodialysis or ambulatory peritoneal dialysis allowed

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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: exatecan mesylate|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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unspecified adult solid tumor, protocol specific