Lobradimil and Carboplatin in Treating Children With Brain Tumors

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. Lobradimil may increase the effectiveness of a chemotherapy drug by making tumor cells more sensitive to the drug. PURPOSE: Phase II trial to study the effectiveness of carboplatin and lobradimil in treating children with brain tumors that have not responded to previous treatment.

Detailed Description
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OBJECTIVES: Determine the objective response rate in patients with recurrent or refractory childhood brain tumors treated with lobradimil and carboplatin. Determine the time to progression in patients treated with this regimen. Assess the toxicity of this regimen in this patient population. Determine the quality of life of patients treated with this regimen. OUTLINE: This is a multicenter study. Patients are stratified according to histology (high-grade glioma vs low-grade glioma vs brainstem or visual pathway glioma vs medulloblastoma/primitive neuroectodermal tumor vs ependymoma). (Brainstem glioma stratum closed to accrual as of 12/21/2000.) (High-grade glioma stratum closed to accrual as of 01/08/2002.) Patients receive carboplatin IV over 15 minutes and lobradimil IV over 10 minutes on days 1 and 2. Treatment repeats every 4 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity. After completion of course 12, patients may receive additional courses at the discretion of the institutional investigator. Quality of life is assessed at baseline and then every 3 courses. Patients are followed every 3 months for 1 year or until evidence of disease progression or initiation of a new therapy. PROJECTED ACCRUAL: A maximum of 146 patients will be accrued for this study within 2-4 years.

Official Title
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A Phase II Trial of Intravenous Cereport (RMP-7) and Carboplatin in Childhood Brain Tumors

Conditions
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Brain and Central Nervous System Tumors

Intervention / Treatment
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* Drug: carboplatin
* Drug: lobradimil


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed childhood brain tumor that is recurrent or refractory or for which no standard chemotherapy exists High-grade glioma (anaplastic astrocytoma or glioblastoma multiforme) (High-grade glioma stratum closed to accrual as of 01/08/2002) Low-grade glioma Medulloblastoma/primitive neuroectodermal tumor (PNET) Ependymoma Brainstem tumor or visual pathway glioma (with radiographic evidence only) (Brainstem glioma stratum closed to accrual as of 12/21/2000) Evidence of recurrent or progressive disease after front-line therapy documented as an increase in tumor size or appearance of new lesion(s) on MRI Patients who did not previously receive radiotherapy as front-line therapy are eligible at time of second recurrence if the first recurrence was treated with radiotherapy only Measurable disease in at least 2 dimensions by MRI Diffuse meningeal involvement not considered measurable if it is the only site of disease Disease must not be limited to the meninges No metastases outside of the CNS PATIENT CHARACTERISTICS: Age: 21 and under at diagnosis Performance status: ECOG 0-2 Life expectancy: At least 8 weeks Hematopoietic: Absolute granulocyte count at least 1,000/mm^3 Hemoglobin at least 8.0 g/dL (transfusion allowed) Platelet count at least 100,000/mm^3 Hepatic: Bilirubin less than 1.5 times upper limit of normal (ULN) SGPT no greater than 2.5 times ULN No significant hepatic illness Renal: Creatinine within limits as defined below by age: Age 5 and under: less than 1.2 mg/dL Age 6 to 10: less than 1.5 mg/dL Age 11 to 15: less than 1.8 mg/dL Age 16 and over: less than 2.4 mg/dL Cardiovascular: No significant cardiac illness Pulmonary: No significant pulmonary illness Other: No significant systemic illness or organ dysfunction that would preclude study No allergic reaction to platinum-containing compounds Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: At least 72 hours since filgrastim (G-CSF) No concurrent biologic therapy for brain tumor Chemotherapy: See Disease Characteristics No prior carboplatin or lobradimil No more than 1 prior chemotherapy regimen for high-grade glioma, low-grade glioma, or ependymoma No more than 2 prior chemotherapy regimens for medulloblastoma/PNET At least 4 weeks since prior nitrosoureas (2 weeks if also received stem cell/bone marrow rescue) At least 2 weeks since any other prior myelosuppressive chemotherapy and recovered No other concurrent chemotherapy for brain tumor Endocrine therapy: Concurrent corticosteroids for management of tumor-related edema allowed Radiotherapy: See Disease Characteristics At least 6 weeks since prior radiotherapy to measurable disease and recovered No concurrent radiotherapy for brain tumor Surgery: No concurrent surgery except for ventriculo-peritoneal shunt placement or revision Other: At least 24 hours since prior vasodilating agents, angiotensin-converting enzyme inhibitors, calcium channel blockers, or beta-blockers

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: carboplatin|nan|
|Drug: lobradimil|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 low-grade cerebral astrocytoma, recurrent childhood supratentorial primitive neuroectodermal tumor, recurrent childhood cerebellar astrocytoma, recurrent childhood cerebral astrocytoma, recurrent childhood medulloblastoma, untreated childhood visual pathway and hypothalamic glioma, recurrent childhood visual pathway and hypothalamic glioma, recurrent childhood ependymoma