RATIONALE: Radiation therapy uses x-rays to damage tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Peripheral stem cell transplantation may allow doctors to give higher doses of radiation therapy and chemotherapy and kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of radiation therapy, chemotherapy and peripheral stem cell transplantation in treating patients with primitive neuroectodermal tumors.

Condition	Treatment or Intervention	Phase
disseminated neuroblastoma untreated childhood supratentorial primitive neuroectodermal and pineal tumors regional neuroblastoma stage IVS neuroblastoma untreated childhood medulloblastoma stage IV peripheral primitive neuroectodermal tumor newly diagnosed childhood ependymoma	Drug: carboplatin  Drug: cyclophosphamide  Drug: filgrastim  Drug: thiotepa  Drug: vincristine	Phase II

Further Study Details: 

OBJECTIVES: I. Determine the safety of postradiotherapy high dose consolidation chemotherapy with peripheral blood stem cell (PBSC) support in patients with high risk primitive neuroectodermal tumors. II. Determine the safety of delaying radiotherapy by approximately one month in these patients. III. Determine the maximum tolerated dose of thiotepa in these patients. IV. Determine the toxic effects of intensive chemotherapy with PBSC support in these patients. V. Assess the time to hematopoietic recovery after PBSC infusion when intensive chemotherapy is used following craniospinal radiotherapy in these patients. VI. Determine the overall and event free survival of these patients.

PROTOCOL OUTLINE: This is a dose escalation study of thiotepa during consolidation therapy. Induction: Patients receive induction therapy within 31 days of initial surgery. This consists of vincristine IV on day 0, cyclophosphamide IV over 1 hour on days 0 and 1, and filgrastim (G-CSF) subcutaneously (SQ) beginning on day 2 and continuing for at least 7-10 days. Peripheral blood stem cells (PBSC) are then collected. Chemoradiotherapy: After blood cell counts recover, and within 28 days of starting induction, patients begin chemoradiotherapy. Patients receive vincristine IV on day 0 and then once a week for 7 more weeks. Radiotherapy is administered 5 days a week, for 6 weeks, beginning within the same week as the start of vincristine. Consolidation: Therapy begins 4-6 weeks after the last radiation treatment in the absence of disease progression. The first and third course are the same and consist of vincristine IV on day 0, carboplatin IV over 1 hour on days 0 and 1, thiotepa IV over 3 hours on days 2-4, and G-CSF SQ daily beginning on day 7. PBSC are reinfused on day 7. The second course consists of vincristine IV on day 0, carboplatin IV over 1 hour on days 0 and 1, cyclophosphamide IV over 1 hour on days 2 and 3, and G-CSF SQ daily beginning on day 5. PBSC are reinfused on day 5. Each course lasts 21 days. For consolidation therapy, cohorts of 6-12 patients each receive escalating doses of thiotepa until the maximum tolerated dose (MTD) is reached. The MTD is defined as the dose at which no more than 2 of 12 patients experience dose limiting toxicity. Patients are followed every 3 months for 1 year, every 6 months for 2 years, then annually thereafter.

PROJECTED ACCRUAL: A total of 24-56 patients will be accrued for this study within 2.5-3.5 years.

Ages Eligible for Study:  3 Years   -   21 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically proven primitive neuroectodermal tumor (PNET) of one of the following types: Atypical teratoid/rhabdoid tumor Medulloblastoma; Desmoplastic medulloblastoma; Ependymoblastoma; Medullomyoblastoma; Spongioblastoma; Spongioblastoma polare; Primitive polar spongioblastoma; Medulloepithelioma; Neuroblastoma; Pineoblastoma
• No M4 disease
• Posterior fossa PNET must be M1-3 or M0 with greater than 1.5 cm2 residual disease
• Nonposterior fossa PNET and other types must be M0-3 If M3, must show clear evidence of tumor on MRI
• No marrow involvement

--Prior/Concurrent Therapy--

• No prior therapy for tumor, including urgent radiotherapy; Steroids for increased intracranial pressure allowed

--Patient Characteristics--

• Age: 3 to 21
• Performance status: Not specified
• Life expectancy: Not specified
• Hematopoietic: Absolute neutrophil count at least 1000/mm3; Platelet count at least 150,000/mm3 (no platelet transfusions); Hemoglobin at least 10 g/dL (red cell transfusions allowed)
• Hepatic: Bilirubin less than 1.5 times upper limit of normal (ULN); AST or ALT less than 2.5 times ULN
• Renal: Creatinine clearance or GFR at least 70 mL/min
• Cardiovascular: Shortening fraction greater than 27% by echocardiogram OR Ejection fraction greater than 47% by MUGA
• Pulmonary: FEV1/FVC greater than 60% except for children who: Are uncooperative; Have no dypsnea at rest; Have no exercise intolerance; Have pulse oximetry greater than 94% in room air
• Other: Not pregnant or nursing

California
      Children's Hospital Los Angeles, Los Angeles,  California,  90027-0700,  United States
      Children's Hospital of Orange County, Orange,  California,  92668,  United States
      Jonsson Comprehensive Cancer Center, UCLA, Los Angeles,  California,  90095-1781,  United States
Colorado
      Children's Hospital of Denver, Denver,  Colorado,  80218,  United States
District of Columbia
      Children's National Medical Center, Washington,  District of Columbia,  20010-2970,  United States
Minnesota
      University of Minnesota Cancer Center, Minneapolis,  Minnesota,  55455,  United States
New York
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States
      NYU School of Medicine's Kaplan Comprehensive Cancer Center, New York,  New York,  10016,  United States
Ohio
      Children's Hospital Medical Center - Cincinnati, Cincinnati,  Ohio,  45229-3039,  United States
      Children's Hospital of Columbus, Columbus,  Ohio,  43205-2696,  United States
Oregon
      Oregon Cancer Center at Oregon Health Sciences University, Portland,  Oregon,  97201-3098,  United States
Texas
      University of Texas - MD Anderson Cancer Center, Houston,  Texas,  77030,  United States
Washington
      Fred Hutchinson Cancer Research Center, Seattle,  Washington,  98109,  United States

Study chairs or principal investigators

H. Stacy Nicholson,  Study Chair,  Children's Cancer Group   

Study ID Numbers:  CDR0000067006; CCG-99702
Record last reviewed:  May 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003846
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08