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
Study type: Interventional
Phase: Phase 2

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.
    

Detailed description: 
      Researchers have used high doses of combination chemotherapy followed by a stem cell rescue
      to treat recurrent brain tumors with moderate success. High dose chemotherapy with stem cell
      rescue has resulted in long term survival of about 25% in patients with several different
      types of recurrent brain tumors. Stem cells are cells in the bone marrow that produce blood
      cells. The stem cells are collected from the blood of the patient before the high dose
      chemotherapy. Patients are given high doses of chemotherapy to kill every brain tumor cell,
      but in the process the cells of the bone marrow are also killed. The previously collected
      stem cells are then infused into the patient to rescue the bone marrow and allow for healthy
      blood cells to re-populate and grow in the bone marrow. Initial studies used the drug
      etoposide along with carboplatin and thiotepa for the high dose chemotherapy. Patients had
      severe side effects, especially severe mouth-sores, thought mainly due to the etoposide, and
      some patients died from these side effects.

      Recent studies have shown that a new drug, temozolomide, is active against some types of
      brain tumors. When it was given as a single drug to children with solid tumors, the side
      effects were considered to be tolerable. Temozolomide is given by mouth. In this study,
      researchers want to give high dose chemotherapy that includes the drugs temozolomide in place
      of etoposide, along with thiotepa and carboplatin. Patients will then be given their own stem
      cells back to rescue the bone marrow from the chemotherapy. A preliminary trial using this
      new drug combination was performed and has shown that patients tolerate this drug
      combination, even at the very high doses that will be used in this protocol.

      Another drug that is being used in pediatric cancer treatment is called 13-cis-retinoic acid.
      This drug is closely related to vitamin A. It is taken by mouth. Cancer cells are immature
      cells that have not "grown up" into adult cells that do work in the body. 13-cis-retinoic
      acid is thought to act on some types of cancer cells to make them mature into cells that
      function in the body. It has also been shown in the laboratory to cause some brain tumor
      cells to undergo apoptosis. It has been used in other types of pediatric cancers and research
      is just beginning to use it for treatment of recurrent brain tumors. In this study
      researchers want to give you 13-cis-retinoic acid for 6 months after you recover from the
      high dose chemotherapy with stem cell rescue.
    

Intervention name(s): temozolomide, thiotepa, carboplatin, 13-cis-retinoic acid
Intervention type(s): Drug
Intervention description(s): 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
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Recurrent or refractory medulloblastoma/PNET; CNS germ cell tumors; Ependymomas; AT/RT; High grade glioma; Other malignant brain tumors