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 transplantation 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: Phase II trial to study the effectiveness of combination chemotherapy followed by surgery or radiation therapy and peripheral stem cell transplantation in treating patients who have recurrent medulloblastoma or primitive neuroectodermal and pineal tumors.

Condition	Treatment or Intervention	Phase
recurrent childhood supratentorial primitive neuroectodermal tumors recurrent childhood medulloblastoma	Drug: carboplatin  Drug: cyclophosphamide  Drug: filgrastim  Drug: thiotepa  Procedure: biological response modifier therapy  Procedure: bone marrow ablation with stem cell support  Procedure: chemotherapy  Procedure: colony-stimulating factor therapy  Procedure: conventional surgery  Procedure: cytokine therapy  Procedure: peripheral blood stem cell transplantation  Procedure: radiation therapy  Procedure: surgery	Phase II

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.

Ages Eligible for Study:  up to  20 Years,  Genders Eligible for Study:  Both

Criteria

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

Ireland
      Our Lady's Hospital for Sick Children, Crumlin,  12,  Ireland; Recruiting
United Kingdom, England
      Addenbrooke's Hospital at Cambridge University Hospitals NHS Foundation Trust, Cambridge,  England,  CB2 2QQ,  United Kingdom; Recruiting
      Birmingham Children's Hospital, Birmingham,  England,  B4 6NH,  United Kingdom; Recruiting
      Bristol Royal Hospital for Children, Bristol,  England,  BS2 8BJ,  United Kingdom; Recruiting
      Children's Hospital - Sheffield, Sheffield,  England,  S10 2TH,  United Kingdom; Recruiting
      Great Ormond Street Hospital for Children NHS Trust, London,  England,  WC1N 3JH,  United Kingdom; Recruiting
      Leicester Royal Infirmary, Leicester,  England,  LE1 5WW,  United Kingdom; Recruiting
      Manchester Children's Hospitals (NHS Trust), Manchester,  England,  M27 1HA,  United Kingdom; Recruiting
      Meyerstein Institute of Oncology at University College of London Hospitals, London,  England,  WIT 3AA,  United Kingdom; Recruiting
      Newcastle Upon Tyne Hospitals NHS Trust, Newcastle upon Tyne,  England,  NE7 7DN,  United Kingdom; Recruiting
      Oxford Radcliffe Hospital, Oxford,  England,  0X3 9DU,  United Kingdom; Recruiting
      Queen's Medical Centre, Nottingham,  England,  NG7 2UH,  United Kingdom; Recruiting
      Royal Liverpool Children's Hospital, Alder Hey, Liverpool,  England,  L12 2AP,  United Kingdom; Recruiting
      Royal Marsden NHS Foundation Trust - Surrey, Sutton,  England,  SM2 5PT,  United Kingdom; Recruiting
      Saint Bartholomew's Hospital, London,  England,  EC1A 7BE,  United Kingdom; Recruiting
      Southampton General Hospital, Southampton,  England,  SO16 6YD,  United Kingdom; Recruiting
      St. James's University Hospital at Leeds Teaching Hospital NHS Trust, Leeds,  England,  LS9 7TF,  United Kingdom; Recruiting
United Kingdom, Northern Ireland
      Royal Belfast Hospital for Sick Children, Belfast,  Northern Ireland,  BT12 6BE,  United Kingdom; Recruiting
United Kingdom, Scotland
      Aberdeen Royal Infirmary, Aberdeen,  Scotland,  AB25 2ZN,  United Kingdom; Recruiting
      Royal Hospital for Sick Children, Glasgow,  Scotland,  G3 8SJ,  United Kingdom; Recruiting
      Royal Hospital for Sick Children, Edinburgh,  Scotland,  United Kingdom; Recruiting

Study chairs or principal investigators

Barry Pizer, MD,  Study Chair,  Royal Liverpool Children's Hospital, Alder Hey   

Study ID Numbers:  CDR0000068910; UKCCSG-CNS-2000-01; EU-20105
Record last reviewed:  October 2001
Record first received:  October 11, 2001
ClinicalTrials.gov Identifier:  NCT00025077
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2004-11-08