SCH 66336 in Treating Children With Recurrent or Progressive Brain Tumors

Study Overview
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Brief Summary
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RATIONALE: SCH 66336 may stop the growth of tumor cells by blocking the enzymes necessary for cancer cell growth. PURPOSE: This phase I trial is studying the side effects and best dose of SCH 66336 in treating children with recurrent or progressive brain tumors.

Detailed Description
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OBJECTIVES: Determine the qualitative and quantitative toxicity of SCH 66336 in children with recurrent or progressive brain tumors. Estimate the maximum tolerated dose of this drug in these patients. Describe the pharmacokinetics of this drug with and without dexamethasone in these patients. Investigate the efficacy of this drug in these patients. OUTLINE: This is a dose-escalation study. Patients receive oral SCH 66336 twice daily. Treatment repeats every 4 weeks for a total of 26 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 1-6 patients receive escalating doses of SCH 66336 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which it is predicted that 20% of patients may experience dose-limiting toxicity. An additional 6 patients are treated at the determined MTD. Patients are followed within 30 days of the last administration of the study drug and then for up to 3 months. PROJECTED ACCRUAL: Approximately 25 patients will be accrued for this study.

Official Title
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Phase I Trial Of Escalating Oral Doses Of SCH 66336 In Pediatric Patients With Refractory Or Recurrent Brain Tumors

Conditions
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Brain and Central Nervous System Tumors

Intervention / Treatment
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* Drug: lonafarnib


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed recurrent or progressive (refractory) brain tumors Histologic confirmation waived for brainstem gliomas Bone marrow involvement allowed if transfusion independent PATIENT CHARACTERISTICS: Age: 21 and under Performance status: Lansky 60-100% OR Karnofsky 60-100% Life expectancy: More than 8 weeks Hematopoietic: See Disease Characteristics Absolute neutrophil count greater than 1,000/mm^3 Platelet count greater than 75,000/mm^3 Hemoglobin greater than 9 g/dL Hepatic: Bilirubin no greater than upper limit of normal SGPT and SGOT less than 2.5 times normal Albumin greater than 3 g/dL PT/PTT no greater than 120% upper limit of normal No overt hepatic disease Renal: Creatinine no greater than 1.5 times normal OR Glomerular filtration rate greater than 70 mL/min No overt renal disease Cardiovascular: No overt cardiac disease Pulmonary: No overt pulmonary disease Other: Neurologic deficits allowed if stable for at least 1 week prior to study More than 3rd percentile weight for height Able to swallow pills No uncontrolled infection No known or suspected allergy to poloxamer 188, croscarmellose sodium, silicon dioxide, or magnesium stearate I Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for up to 10 weeks after study PRIOR CONCURRENT THERAPY: Biologic therapy: More than 6 months since prior bone marrow transplantation More than 1 week since prior growth factors Chemotherapy: At least 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas) and recovered Endocrine therapy: Concurrent dexamethasone allowed if on stable dose for at least 1 week prior to study Concurrent oral contraceptives or other hormonal contraceptive methods allowed Radiotherapy: More than 6 weeks since prior substantial bone marrow radiotherapy More than 3 months since prior craniospinal radiotherapy (more than 24 Gy) or total body irradiation More than 2 weeks since prior focal radiotherapy for symptomatic metastatic sites Surgery: Not specified Other: No concurrent enzyme-inducing anticonvulsant drugs No other concurrent anticancer or experimental drug therapy

Ages Eligible for Study
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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: lonafarnib|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicities of SCH 66336 in children and adolescents with refractory CNS cancers |  |  | 
| Maximum tolerated dose of SCH 66336 |  | Four weeks | 
| Pharmacokinetics of SCH 66336 |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor response to SCH 66336 |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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childhood craniopharyngioma, childhood central nervous system germ cell tumor, childhood oligodendroglioma, childhood choroid plexus tumor, childhood grade I meningioma, childhood grade II meningioma, childhood grade III meningioma, recurrent childhood cerebellar astrocytoma, recurrent childhood cerebral astrocytoma, recurrent childhood medulloblastoma, recurrent childhood visual pathway and hypothalamic glioma, recurrent childhood ependymoma, childhood atypical teratoid/rhabdoid tumor, childhood spinal cord neoplasm