Temozolomide,Thiotepa and Carboplatin With Autologous Stem Cell Rescue Followed by 13-cis-retinoic Acid in Patients With Recurrent/Refractory Malignant Brain Tumors
Condition: Brain Tumors
MeSH terms: Brain Neoplasms
Intervention: temozolomide, thiotepa, carboplatin, 13-cis-retinoic acid
Intervention description: 13-cis-retinoic acid, when absorbed, may be subject to first-pass metabolism and subsequent plasma (and tumor) concentrations will depend on the rate of metabolism to the inactive 4-oxo metabolite.
Intervention MeSH terms: Carboplatin; Temozolomide; Thiotepa; Tretinoin; Isotretinoin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 46.0
Sex: All
Minimum age: 6 Months
Maximum age: 21 Years
Healthy volunteers: No
Keywords: Recurrent or refractory medulloblastoma/PNET; CNS germ cell tumors; Ependymomas; AT/RT; High grade glioma; Other malignant brain tumors

Summary:

      The purpose of this study is to:

      Find out how safe and effective (by monitoring the good and/or bad effects) treatment with
      high dose temozolomide, thiotepa and carboplatin with stem cell rescue followed by
      13-cis-retinoic acid has on children and adolescents with recurrent/refractory brain tumors

      Find out how the body uses 13-cis-retinoic acid by studying the your blood levels and
      proteins in the blood that break down the 13-cis-retinoic acid

      Determine how well 13-cis-retinoic acid penetrates into the spinal fluid.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients with recurrent or refractory medulloblastoma/PNET, CNS germ cell tumors,
             ependymomas, AT/RT, high grade glioma and other malignant brain tumors. Brainstem
             gliomas are eligible if residual disease is < 1.5cc and if the patient is off
             decadron.

          2. Patients must have recurrent or refractory disease following at least one prior course
             of therapy and must have minimal residual disease defined as < 1.5 cm2 of enhancement.
             Patients with + CSF cytology, linear or fine nodular leptomeningeal disease are
             eligible.

          3. Adequate hematologic, renal, liver, and cardiac function as demonstrated by laboratory
             values performed within 21 days, inclusive, prior to administration of temozolomide.

          4. Patients must have an adequate number of autologous stem cells available defined as a
             minimum of 2 x 106 CD 34+ cells/kg and preferably at least 5 x 106 CD 34+ cells/kg.

        Exclusion Criteria:

          1. Previous myeloablative therapy

          2. Frequent vomiting or medical condition that could interfere with oral medication
             intake (e.g., partial bowel obstruction)

          3. Previous or concurrent malignancies at other sites with the exception of surgically
             cured carcinoma in-situ of the cervix and basal or squamous cell carcinoma of the
             skin. Patients with prior malignancies which have not required anti-tumor treatment
             within the preceding 24 months are eligible.