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Temozolomide,Thiotepa and Carboplatin With Autologous Stem Cell Rescue Followed by 13-cis-retinoic Acid in Patients With Recurrent/Refractory Malignant Brain Tumors

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Children's Hospitals and Clinics of Minnesota
Schneider Children's Hospital
Information provided by (Responsible Party):
New York University School of Medicine
ClinicalTrials.gov Identifier:
NCT00528437
First received: September 10, 2007
Last updated: May 27, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Brain Tumors
Drug: temozolomide, thiotepa, carboplatin, 13-cis-retinoic acid
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: NYU 05-40 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

Resource links provided by NLM:


Further study details as provided by New York University School of Medicine:

Primary Outcome Measures:
  • • To assess the event-free survival and overall survival of patients with recurrent or refractory medulloblastoma/ primitive neuroectodermal tumors [ Time Frame: Day +42 and Day +77 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To evaluate the toxicity of of 13-cis-retinoic acid following high dose temozolomide, thiotepa and carboplatin with ASCR. [ Time Frame: One year ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 36
Study Start Date: October 2005
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Myeloablative Chemo-Temozolomide, Thiotepa, and Carboplatin. Drug: temozolomide, thiotepa, carboplatin, 13-cis-retinoic acid
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.

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.

  Eligibility

Ages Eligible for Study:   6 Months to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00528437

Locations
United States, Arizona
Phoenix Children's Hospital
Pheonix, Arizona, United States, 85016
United States, Georgia
Emory University
Altanta, Georgia, United States, 30322
United States, Hawaii
Hawaii Pacific Health
Lihue, Hawaii, United States, 96766
United States, Illinois
Children's Memorial Hospital
Chicago, Illinois, United States, 60614
United States, Indiana
Riley Hospital for Children
Indianapolis, Indiana, United States, 46202
United States, Minnesota
Children's Hospital and Clinics of Minnesota
Minneapolis, Minnesota, United States, 55404
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
Steven and Alexandra Cohen Children's Medical Center of New York- North Shore LIJ
New Hyde Park, New York, United States, 11040
NYU Hassenfeld Center
New York, New York, United States, 10016
United States, Ohio
Nationwide Children's Hospital
Columbus, Ohio, United States, 43205
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
United States, South Carolina
Medical Univ. of South Carolina
Charleston, South Carolina, United States, 29425
United States, Tennessee
Vanderbilt Univ.
Nashville, Tennessee, United States, 37240
United States, Texas
Children's Medical Center of Dallas
Dallas, Texas, United States, 75235
MD Anderson Cancer Center (MDACC)
Houston, Texas, United States, 77030
United States, Virginia
Virginia Commonwealth Univ.
Richmond, Virginia, United States, 23284
Canada, Ontario
Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Sponsors and Collaborators
New York University School of Medicine
Children's Hospitals and Clinics of Minnesota
Schneider Children's Hospital
Investigators
Principal Investigator: Sharon L Gardner, M.D. New York University School of Medicine
  More Information

No publications provided

Responsible Party: New York University School of Medicine
ClinicalTrials.gov Identifier: NCT00528437     History of Changes
Other Study ID Numbers: NYU 05-40 H12853, PBMTC ONC-032P
Study First Received: September 10, 2007
Last Updated: May 27, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by New York University School of Medicine:
Recurrent or refractory medulloblastoma/PNET
CNS germ cell tumors
Ependymomas
AT/RT
High grade glioma
Other malignant brain tumors

Additional relevant MeSH terms:
Brain Neoplasms
Neoplasms
Brain Diseases
Central Nervous System Diseases
Central Nervous System Neoplasms
Neoplasms by Site
Nervous System Diseases
Nervous System Neoplasms
Carboplatin
Dacarbazine
Isotretinoin
Temozolomide
Thiotepa
Tretinoin
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Dermatologic Agents
Immunologic Factors
Immunosuppressive Agents
Keratolytic Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014