Irinotecan in Treating Children With Refractory or Advanced Solid Tumors Who Are Receiving Anticonvulsants

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 irinotecan in treating children with refractory or advanced solid tumors who are receiving anticonvulsants.

Detailed Description
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OBJECTIVES: Determine the maximum tolerated dose of irinotecan in children with refractory or advanced solid tumors receiving anticonvulsants. Determine the dose-limiting toxicity of irinotecan in this patient population. Evaluate the pharmacokinetic behavior of this treatment regimen in these patients. Determine, preliminarily, the antitumor activity of this treatment regimen in these patients. OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to type of concurrent anticonvulsant (enzyme activating anticonvulsants vs valproic acid vs other anticonvulsants). Patients receive irinotecan IV over 1 hour daily for 5 days. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of irinotecan until the maximum tolerated dose (MTD) is reached. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Patients are followed every 6 months for up to 4 years and then annually thereafter. PROJECTED ACCRUAL: A total of 3-25 patients will be accrued for this study.

Official Title
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A Phase I Study of Irinotecan in Patients With Refractory Solid Tumors Who Are Concomitantly Receiving Anticonvulsants

Conditions
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Unspecified Childhood Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: irinotecan hydrochloride


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed malignancy refractory to conventional therapy or for which no conventional therapy exists Histologic confirmation not required for brain stem tumors Concurrently on anticonvulsants at a steady level for at least 2 weeks PATIENT CHARACTERISTICS: Age: 1-21 years old Performance status: Karnofsky 50-100% (over 10 years of age) Lansky 50-100% (10 years of age or under) Life expectancy: At least 8 weeks Hematopoietic: Neutrophil count at least 1,000/mm3 Platelet count at least 100,000/mm3 (transfusion independent) Hemoglobin at least 8.0 g/dL (red blood cell transfusions allowed) Hepatic: Bilirubin no greater than 1.5 times normal for age SGPT less than 5 times normal for age Albumin at least 2 g/dL Renal: Creatinine no greater than 1.5 times normal for age OR Creatinine clearance or radioisotope glomerular filtration rate at least lower limit of normal for age Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No uncontrolled infection No evidence of active graft-vs-host disease Neurologic deficits for CNS tumors stable for at least 2 weeks prior to study PRIOR CONCURRENT THERAPY: Biologic therapy: At least 1 week since prior antineoplastic biologic therapy At least 6 months since prior allogeneic stem cell transplantation At least 1 week since prior growth factors No concurrent sargramostim (GM-CSF) No concurrent prophylactic growth factors during first course of study therapy Recovered from prior immunotherapy Chemotherapy: At least 2 weeks since prior myelosuppressive chemotherapy (4 weeks for nitrosourea) and recovered Endocrine therapy: Concurrent dexamethasone for CNS tumors with increased intracranial pressure allowed if dose stable or decreasing for at least 2 weeks prior to study Radiotherapy: At least 2 weeks since prior local palliative radiotherapy (small part) At least 6 months since prior craniospinal radiotherapy At least 6 months since prior radiotherapy to at least 50% of pelvis At least 6 weeks since prior substantial bone marrow radiotherapy Recovered from prior radiotherapy Surgery: Not specified Other: No other concurrent investigational agent

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 21 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: irinotecan hydrochloride|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerable dose (MTD) of irinotecan |  |  | 

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