DX-8951f in Treating Children With Advanced Solid Tumors or Lymphomas

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. PURPOSE: Phase I trial to study the effectiveness of DX-8951f in treating children who have advanced solid tumors or lymphomas that have not responded to previous therapy.

Detailed Description
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OBJECTIVES: Determine the maximum tolerated dose of exatecan mesylate (DX-8951f) with and without filgrastim (G-CSF) in pediatric patients with advanced solid tumors or lymphomas. Determine the toxic effects, including dose-limiting toxicity, of exatecan mesylate in these patients. Determine the pharmacokinetics of exatecan mesylate in these patients. Determine the recommended dose of exatecan mesylate for phase II study. Determine the antitumor activity of this regimen in these patients. OUTLINE: This is a dose-escalation study of exatecan mesylate (DX-8951f). Patients are stratified according to prior treatment (minimally treated vs heavily treated). Patients receive exatecan mesylate IV over 30 minutes daily for 5 days. Patients in dose levels 5 and above also receive filgrastim (G-CSF) subcutaneously beginning on day 6 and continuing for at least 7 days or until blood counts recover. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 1-6 patients receive escalating doses of exatecan mesylate with and without G-CSF until the maximum tolerated dose (MTD) is determined. 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 3 months. PROJECTED ACCRUAL: Approximately 45 patients will be accrued for this study.

Official Title
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A Phase I Dose Escalation Study of Intravenous DX-8951f Administered Daily for Five Days Every Three Weeks to Pediatric Patients With Advanced Solid Tumors and Lymphomas

Conditions
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Brain and Central Nervous System Tumors, Lymphoma, Unspecified Childhood Solid Tumor, Protocol Specific

Intervention / Treatment
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* Biological: filgrastim
* Drug: exatecan mesylate


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed advanced solid tumors, including brain tumors and lymphomas, that have failed standard therapy (surgery, radiotherapy, endocrine therapy, or chemotherapy) or for which no standard therapy exists Histology requirement waived for brain stem gliomas PATIENT CHARACTERISTICS: Age: 21 and under at diagnosis Performance status: ECOG 0-2 Life expectancy: At least 8 weeks Hematopoietic: Absolute neutrophil count at least 750/mm^3 Platelet count at least 75,000/mm^3 Hemoglobin at least 8.5 g/dL Hepatic: Bilirubin no greater than 1.5 mg/dL SGOT or SGPT no greater than 2.5 times upper limit of normal (ULN) (5 times ULN if liver metastases) Renal: Creatinine no greater than 1.5 times ULN OR GFR at least 70 mL/min Other: Not pregnant or nursing Negative pregnancy test No history of severe or life-threatening hypersensitivity to camptothecin analogs HIV negative No other concurrent severe or uncontrolled medical illness No systemic infection PRIOR CONCURRENT THERAPY: Biologic therapy: Recovered from prior immunotherapy Chemotherapy: See Disease Characteristics Recovered from prior chemotherapy Endocrine therapy: See Disease Characteristics Radiotherapy: See Disease Characteristics At least 4 weeks since prior extensive radiotherapy involving cranial, whole pelvic, or at least 25% of bone marrow reserve Recovered from prior radiotherapy Concurrent localized radiotherapy for pain allowed Surgery: See Disease Characteristics Recovered from prior surgery Other: No other concurrent antitumor therapy No concurrent drugs that induce or inhibit CYP3A enzyme

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 |
| --- |
|Biological: filgrastim|nan|
|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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childhood infratentorial ependymoma, childhood supratentorial ependymoma, childhood craniopharyngioma, stage III childhood lymphoblastic lymphoma, stage IV childhood lymphoblastic lymphoma, recurrent childhood lymphoblastic lymphoma, childhood central nervous system germ cell tumor, unspecified childhood solid tumor, protocol specific, stage III childhood Hodgkin lymphoma, stage IV childhood Hodgkin lymphoma, recurrent/refractory childhood Hodgkin lymphoma, childhood high-grade cerebral astrocytoma, childhood oligodendroglioma, childhood choroid plexus tumor, stage III childhood small noncleaved cell lymphoma, stage III childhood large cell lymphoma, stage IV childhood small noncleaved cell lymphoma, stage IV childhood large cell lymphoma, recurrent childhood small noncleaved cell lymphoma, recurrent childhood large cell lymphoma, untreated childhood brain stem glioma, recurrent childhood brain stem glioma, untreated childhood supratentorial primitive neuroectodermal tumor, recurrent childhood supratentorial primitive neuroectodermal tumor, untreated childhood cerebellar astrocytoma, recurrent childhood cerebellar astrocytoma, recurrent childhood cerebral astrocytoma, untreated childhood medulloblastoma, recurrent childhood medulloblastoma, untreated childhood visual pathway and hypothalamic glioma, recurrent childhood visual pathway and hypothalamic glioma, newly diagnosed childhood ependymoma, recurrent childhood ependymoma