Combination Chemotherapy, Surgery or Radiation Therapy, and Peripheral Stem Cell Transplant in Treating Patients With Recurrent Medulloblastoma or Primitive Neuroectodermal and Pineal 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. Giving a chemotherapy drug before surgery or radiation therapy may shrink the tumor so that it can be removed during surgery or radiation therapy. Peripheral stem cell transplant may be able to replace immune cells that were destroyed by chemotherapy or radiation therapy and allow doctors to give higher doses of chemotherapy. PURPOSE: This phase II trial is studying how well combination chemotherapy followed by surgery or radiation therapy and peripheral stem cell transplant work in treating patients with recurrent medulloblastoma or primitive neuroectodermal and pineal tumors.

Detailed Description
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OBJECTIVES: Determine the feasibility of cyclophosphamide and surgical resection or radiotherapy followed by thiotepa, carboplatin, and autologous peripheral blood stem cell rescue in patients with recurrent medulloblastoma or supratentorial neuroectodermal and pineal tumors. Determine the acute and chronic toxicity of this regimen in these patients. Determine progression-free and overall survival of patients treated with this regimen. OUTLINE: This is a multicenter study. Cytoreductive Phase: Patients receive cyclophosphamide IV over 1 hour on days 1 and 2 and filgrastim (G-CSF) subcutaneously (SC) once daily beginning on day 7 and continuing until blood counts recover. Treatment repeats after discontinuation of G-CSF for 2-4 courses. Peripheral blood stem cells (PBSC) are harvested after each course of cyclophosphamide. Patients undergo surgical resection or radiotherapy after the completion of chemotherapy. Patients achieving complete response proceed to myeloablative therapy. Myeloablative Phase: Patients receive thiotepa IV over 3 hours on days 1-3. Autologous PBSC are reinfused on day 5 and patients receive G-CSF SC once daily beginning on day 10 and continuing until blood counts recover. Beginning 2 days after the completion of G-CSF, patients receive carboplatin IV over 1 hour on days 1-3. Autologous PBSC are reinfused on day 5 and patients receive G-CSF SC once daily beginning on day 10 and continuing until blood counts recover. Patients are followed at 1, 3, 6, and 12 months. PROJECTED ACCRUAL: Approximately 50 patients will be accrued for this study within 5 years.

Official Title
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Treatment Of Recurrent Central Nervous System Primitive Neuroectodermal Tumors (PNETs) In Children And Adolescents A Strategy Including The Use Of High Dose Thiotepa And High Dose Carboplatin

Conditions
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Brain and Central Nervous System Tumors

Intervention / Treatment
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* Biological: filgrastim
* Drug: carboplatin
* Drug: cyclophosphamide
* Drug: thiotepa
* Procedure: conventional surgery
* Procedure: peripheral blood stem cell transplantation
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed recurrent medulloblastoma or supratentorial primitive neuroectodermal and pineal tumor Nodular/desmoplastic medulloblastoma Medullomyoblastoma Melanotic medulloblastoma Ependymoblastoma Pinealoblastoma Received prior craniospinal radiotherapy OR Relapse in site of prior localized radiotherapy (e.g., relapse after baby brain protocol) PATIENT CHARACTERISTICS: Age: Under 21 Performance status: Lansky 40-100% for ages 1-16 years Karnofsky 40-100% for ages over 16 years Life expectancy: At least 8 weeks Hematopoietic: Neutrophil count at least 1,000/mm^3 Platelet count at least 100,000/mm^3 Hepatic: Bilirubin less than upper limit of normal (ULN) AST less than 2 times ULN Renal: Glomerular filtration rate at least 60 mL/min Other: Not pregnant or nursing Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy Not specified Endocrine therapy Not specified Radiotherapy See Disease Characteristics Surgery Not specified

Ages Eligible for Study
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Maximum Age: 20 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: carboplatin|nan|
|Drug: cyclophosphamide|nan|
|Drug: thiotepa|nan|
|Procedure: conventional surgery|nan|
|Procedure: peripheral blood stem cell transplantation|nan|
|Radiation: radiation therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event-free survival |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxic death rate |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent childhood supratentorial primitive neuroectodermal tumor, recurrent childhood medulloblastoma