RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Peripheral stem cell transplantation or bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of combining temozolomide, thiotepa, and carboplatin followed by peripheral stem cell transplantation or bone marrow transplantation in treating patients who have brain cancer.

Condition	Treatment or Intervention	Phase
adult brain tumor childhood central nervous system germ cell tumor childhood ependymoma Childhood Medulloblastoma childhood supratentorial primitive neuroectodermal tumors	Drug: carboplatin  Drug: filgrastim  Drug: temozolomide  Drug: thiotepa  Procedure: autologous bone marrow transplantation  Procedure: biological response modifier therapy  Procedure: bone marrow ablation with stem cell support  Procedure: bone marrow transplantation  Procedure: chemotherapy  Procedure: colony-stimulating factor therapy  Procedure: cytokine therapy  Procedure: peripheral blood stem cell transplantation	Phase I

Further Study Details: 

OBJECTIVES:

• Determine the maximum tolerated dose of temozolomide in combination with thiotepa and carboplatin followed by autologous peripheral blood stem cell or bone marrow transplantation in patients with recurrent high-grade brain tumors with minimal residual disease or newly-diagnosed malignant glioma with minimal residual disease following irradiation.

OUTLINE: This is a dose-escalation study of temozolomide.

Patients receive filgrastim (G-CSF) subcutaneously (SC) once daily for 3 consecutive days. After the third dose of G-CSF, patients undergo leukapheresis to collect peripheral blood stem cells (PBSC). Patients who do not have adequate PBSC may undergo bone marrow harvest.

Patients then receive oral temozolomide every 12 hours on days -10 to -6 and thiotepa IV over 3 hours and carboplatin IV over 4 hours on days -5 to -3.

PBSC or bone marrow are reinfused on day 0. Beginning on day 1, patients receive G-CSF SC or IV until blood counts recover.

Cohorts of 3-6 patients receive escalating doses of temozolomide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed at day 42, at 3 months, every 3 months for 2 years, every 4 months for 1 year, every 6 months for 1 year, and then annually thereafter.

PROJECTED ACCRUAL: A total of 18-30 patients will be accrued for this study.

Ages Eligible for Study:  1 Year   -   49 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of one of the following malignant brain tumors:
• Anaplastic astrocytoma
• Glioblastoma multiforme
• Anaplastic oligodendroglioma
• Medulloblastoma
• High-grade ependymoma
• Germ cell tumors
• Pineoblastoma
• Other primitive neuroectodermal tumors
• Recurrent disease or resistant to conventional therapy (e.g., surgery, radiotherapy, or standard chemotherapy)
• No prior myeloablative doses of thiotepa OR
• Newly diagnosed malignant glioma with minimal residual disease after prior radiotherapy
• Minimal residual disease is defined as tumor with maximum diameter of less than 1.5 cm by MRI and no corticosteroid dependency

PATIENT CHARACTERISTICS: Age:

• Over 1 to under 50

Performance status:

• Karnofsky 70-100% OR
• Lansky 70-100%

Life expectancy:

• More than 12 weeks

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm3
• Platelet count at least 100,000/mm3
• Hemoglobin at least 10 g/dL (transfusion allowed)

Hepatic:

• Bilirubin less than 1.5 times upper limit of normal (ULN)
• SGOT/SGPT less than 2.5 times ULN
• Alkaline phosphatase less than 2.5 times ULN

Renal:

• Creatinine less than 1.5 times ULN
• Creatinine clearance at least 70 mL/min
• BUN less than 1.5 times ULN

Cardiovascular:

• Ejection fraction greater than 50% OR
• Shortening fraction greater than 27%
• No evidence of myocardial ischemia on EKG if over 40 years of age

Other:

• HIV negative
• No AIDS-related illness
• No frequent vomiting or medical condition that would preclude oral medication (e.g., partial bowel obstruction)
• No other malignancy within the past 2 years except surgically cured carcinoma in situ of the cervix or basal cell or squamous cell skin cancer
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy:

• At least 2 weeks since prior biologic therapy or immunotherapy

Chemotherapy:

• See Disease Characteristics
• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered

Endocrine therapy:

• See Disease Characteristics

Radiotherapy:

• See Disease Characteristics
• At least 6 weeks since prior radiotherapy and recovered
• At least 6 weeks since prior brachytherapy or radiosurgery

Surgery:

• See Disease Characteristics
• Recovered from prior major surgery

New York
      NYU Cancer Institute at New York University Medical Center, New York,  New York,  10016,  United States; Recruiting
Ohio
      Columbus Children's Hospital, Columbus,  Ohio,  43205-2696,  United States; Recruiting
Pennsylvania
      Children's Hospital of Philadelphia, Philadelphia,  Pennsylvania,  19104,  United States; Recruiting
Australia, Western Australia
      Princess Margaret Hospital for Children, Perth,  Western Australia,  6001,  Australia; Recruiting

Study chairs or principal investigators

Sharon L. Gardner, MD,  Study Chair,  New York University School of Medicine   

Study ID Numbers:  CDR0000068973; NYU-0006H; NCI-G01-2022; NCT00025558
Record last reviewed:  February 2002
Last Updated:  April 4, 2005
Record first received:  October 11, 2001
ClinicalTrials.gov Identifier:  NCT00025558
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08