Combination Chemotherapy Followed by Peripheral Stem Cell Transplantation or Bone Marrow Transplantation in Treating Patients With Brain Cancer
Condition: Brain and Central Nervous System Tumors
MeSH terms: Nervous System Neoplasms; Central Nervous System Neoplasms
Study type: Interventional
Phase: Phase 1

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): filgrastim; carboplatin; temozolomide; thiotepa; autologous bone marrow transplantation; peripheral blood stem cell transplantation
Intervention type(s): Biological; Drug; Drug; Drug; Procedure; Procedure
Intervention MeSH terms: Carboplatin; Temozolomide; Thiotepa
Primary purpose: Treatment
Keywords: childhood central nervous system germ cell tumor; recurrent adult brain tumor; adult medulloblastoma; adult glioblastoma; adult anaplastic astrocytoma; adult anaplastic oligodendroglioma; adult mixed glioma; adult central nervous system germ cell tumor; adult pineoblastoma; recurrent childhood supratentorial primitive neuroectodermal tumor; recurrent childhood medulloblastoma; recurrent childhood ependymoma; adult giant cell glioblastoma; adult gliosarcoma; adult anaplastic ependymoma; adult supratentorial primitive neuroectodermal tumor (PNET)