PBMTC ONC-032P, High dose temozolomide, thiotepa and carboplatin with autologous stem cell rescue (ASCR) followed by continuation therapy with 13-cis-retinoic acid in patients with recurrent/refractory malignant brain tumors

Study ID
STU 032011-114

Cancer Related
Yes

Healthy Volunteers
No

Study Sites

  • Children's Medical Center-Dallas
  • UT Southwestern-Other

Contact
Gevel Jackson
214-456-7194
gevel.jackson@childrens.com

Principal Investigator
Victor Aquino

Summary

Patients will first undergo the collection of autologous peripheral blood stem cells following mobilization with filgrastim and/or chemotherapy. Cytoreductive therapy will begin after adequate numbers of stem cells have been collected. Patients will receive Temozolomide (175 mg/m2 /dose or 5.8mg/kg) orally twice daily for five days followed by Thiotepa (300 mg/m2 or 10 mg/kg) and Carboplatin (500 mg/m2 or 16.7 mg/kg for patients and amp;lt;3 years) administered intravenously daily for three days. Autologous stem cells will be reinfused three days following the completion of the chemotherapy. Patients who have not already received their lifetime maximum dose of radiation therapy may receive additional radiation therapy following recovery from the high dose chemotherapy at the discretion of the treating physician. Radiation therapy should start no sooner than 28 days post stem cell reinfusion. Organ toxicity within the radiation field should have resolved. It is highly desirable to start radiation therapy within 42 days after the stem cell reinfusion. Patients will begin therapy with 13-Cis-retinoic acid (160 mg/m2 /day or 5.33 mg/kg/day for patients and amp;lt;12kg) between day +42 and day +77 following ASCR. The 13-cis-retinoic acid will be given orally twice daily for 14 days followed by a 14 day break for a total of 6 cycles (six months).


* Temozolomide is given PO twice a day at a dose of 175 mg/m2/dose bid (or 5.8 mg/kg/dose bid for patients and amp;lt; 3 years of age) for 5 days

* Thiotepa is given at a dose of 300 mg/m2/day (10 mg/kg/day for patients and amp;lt; 3 years of age) IV over 3 hours

* Carboplatin is given by IV infusion over 4 hours immediately after the thiotepa at a dose of 500 mg/m2 (or 16.7 mg/kg for patients and amp;lt; 3 years of age) whichever is lowest

* Filgrastim (G-CSF) is a drug to stimulate the production of white blood cells. It will be given IV or SC starting on the day after the stem cell infusion and continue until enough white blood cells are present in the blood to fight infection. Usually this will require 2 weeks of G-CSF treatment at a dose of 5 ?g/kg/day daily SC (or IV over 4 hours).

Pharmacokinetic studies (Optional): Researchers want to study how the body breaks down and uses the 13-cis-retinoic acid. This is done by measuring levels of the drug in blood samples and by studying enzymes that break down the drug. If patients choose to participate, a single teaspoon blood sample (5 ml) will be taken prior to the first course of 13-cis-retinoic acid treatment. On day 14 of the first course of 13-cis-retinoic acid, one teaspoon of blood will be taken at the following time-points: pretreatment and 1, 2, 4 and 6 hours after oral administration of 13-cis-retinoic acid. Some patients will have spinal taps during their treatment to monitor for tumor growth and tumor cells. For these patients, extra spinal fluid (2-5ml, (1/2)-1 teaspoon) will be collected during one routine spinal tap to measure 13-cis-retinoic acid in the spinal fluid. The spinal tap would be done on the 14th day of first cycle of 13-cis-retinoic acid, two hours after the morning dose of 13-cis-retinoic acid. The purpose of this aspect of the study is to determine the level of 13-cis-retinoic acid that penetrates into the spinal fluid. No genetic testing will be performed on the sample collected.

Participant Eligibility

• 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.
• 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.
• Karnofsky Performance Status or Lansky Performance score > 70%.
• Patients must have an anticipated life expectancy of greater than 12 weeks to be eligible for this study.
• Adequate hematologic, renal, liver, and cardiac function.
• 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.
• Age greater than 6 months of age and less than 21 years.
• Patients must have recovered from any effects of major surgery, chemotherapy or radiation. Patients may not have received chemotherapy (excluding nitrosoureas) within 21 days and may not have received radiation therapy or nitrosoureas within 42 days of starting treatment.
• Patients may have received stereotactic radiation at the time of recurrence as part of their salvage treatment.
• Patients or legal guardians must give written, informed consent.