Radiation Therapy Plus Carboplatin and Lobradimil in Treating Children With Newly Diagnosed Brain Stem Gliomas

Study Overview
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Brief Summary
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RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs such as carboplatin and lobradimil may make the tumor cells more sensitive to radiation therapy. PURPOSE: Phase I trial to study the effectiveness of combining radiation therapy with carboplatin and lobradimil in treating children who have newly diagnosed brain stem gliomas.

Detailed Description
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OBJECTIVES: Determine the maximum tolerated duration of lobradimil plus carboplatin with radiotherapy in patients with newly diagnosed brain stem gliomas. Determine the toxic effects of this treatment regimen in these patients. Assess the response to radiotherapy in patients treated with this regimen. OUTLINE: Patients receive radiotherapy for 5 consecutive days a week for 6.5 weeks, for a total of 33 doses. Patients receive carboplatin IV over 15 minutes followed by lobradimil IV over 10 minutes concurrently with radiotherapy. The first cohort of 3-6 patients receives treatment with carboplatin and lobradimil for the first three weeks of radiotherapy, with the duration of chemotherapy increasing by one week with each subsequent cohort until the maximum duration of 6.5 weeks is reached or until unacceptable toxicity occurs in 2 of 6 patients. Patients are followed at 6 weeks; every 3 months for 2 years; every 6 months for 3 years; and then annually thereafter. PROJECTED ACCRUAL: A total of 15-24 patients will be accrued for this study within 36 months.

Official Title
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Phase I Study of Concurrent Cereport and Carboplatin With Radiation Therapy for Children With Newly-Diagnosed Brain Stem Gliomas

Conditions
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Brain and Central Nervous System Tumors

Intervention / Treatment
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* Drug: carboplatin
* Drug: cereport
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Newly diagnosed diffuse, intrinsic brain stem gliomas Measurable disease No disseminated disease at sites other than brain stem No neurofibromatosis Treatment must begin within 31 days of diagnosis Date of diagnosis will be considered date of surgery in patients undergoing surgical biopsy PATIENT CHARACTERISTICS: Age: 3 to 21 Performance status: Karnofsky 50-100% (over 10 years of age) Lansky 50-100% (10 years of age and under) Life expectancy: At least 2 months Hematopoietic: Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hemoglobin at least 10 g/dL Hepatic: Bilirubin less than 1.5 times upper limit of normal (ULN) SGPT no greater than 2.5 times ULN (4.0 times ULN with antiepileptic or steroid medications) Renal: Creatinine less than ULN for age OR Creatinine clearance or glomerular filtration rate greater than 80 mL/min Other: No history of severe allergic reaction to any platinum-containing compound Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy No concurrent growth factors during therapy with carboplatin Chemotherapy Not specified Endocrine therapy Prior corticosteroids for brain stem glioma are allowed Radiotherapy Not specified Surgery Prior surgery for brain stem glioma is allowed Other At least 24 hours since any of the following medications: Vasodilating compounds Angiotensin-converting enzyme inhibitors Calcium channel blockers Beta blockers No other prior therapy for brain stem glioma

Ages Eligible for Study
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Minimum Age: 3 Years
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

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Radiation Therapy, 33 Doses; Carboplatin 35mg^m2 for 20 Days<br> | Drug: carboplatin<br> <br> * Other names: NSC #241240;Drug: cereport<br> <br> * Other names: IND #60315;Radiation: radiation therapy<br> <br> |
| Experimental: Radiation Therapy, 33 Doses; Carboplatin 35mg^m2 for 25 Days<br> | Drug: carboplatin<br> <br> * Other names: NSC #241240;Drug: cereport<br> <br> * Other names: IND #60315;Radiation: radiation therapy<br> <br> |
| Experimental: Radiation Therapy, 33 Doses; Carboplatin 35mg^m2 for 30 Days<br> | Drug: carboplatin<br> <br> * Other names: NSC #241240;Drug: cereport<br> <br> * Other names: IND #60315;Radiation: radiation therapy<br> <br> |
| Experimental: Radiation Therapy, 33 Doses; Carboplatin 35mg^m2 for 33 Days<br> | Drug: carboplatin<br> <br> * Other names: NSC #241240;Drug: cereport<br> <br> * Other names: IND #60315;Radiation: radiation therapy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival | A MRI scan will be performed six (6) weeks after completion of radiation, plus at three-month intervals thereafter for two years, as long as there is no evidence of progressive disease. Children who are progression-free two years after treatment will have MRI scanning at six-month intervals, thereafter, for three more years |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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untreated childhood brain stem glioma