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

June 17, 2021 updated by: NYU Langone Health

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

46

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

6 months to 21 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Event-free Survival (EFS)
Time Frame: Day +42
EFS will be reported in patients with recurrent or refractory medulloblastoma/ primitive neuroectodermal tumors. EFS is defined as the length of time after primary treatment for a cancer ends that the patient remains free of certain complications or events that the treatment was intended to prevent or delay.
Day +42
Overall Survival (OS)
Time Frame: Day +77
OS will be reported in patients with recurrent or refractory medulloblastoma/ primitive neuroectodermal tumors. OS is defined as the length of time from the start of treatment that patients diagnosed with disease are still alive.
Day +77

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Toxicity of of 13-cis-retinoic Acid
Time Frame: One year
To report the toxicity of of 13-cis-retinoic acid following high dose temozolomide, thiotepa and carboplatin with ASCR.
One year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

NYU Langone Health

Collaborators

Children's Hospitals and Clinics of Minnesota
Schneider Children's Hospital

Investigators

  • Principal Investigator: Sharon L Gardner, MD, NYU Langone Health

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 1, 2005

Primary Completion (Actual)

June 30, 2017

Study Completion (Actual)

December 30, 2017

Study Registration Dates

First Submitted

September 10, 2007

First Submitted That Met QC Criteria

September 11, 2007

First Posted (Estimate)

September 12, 2007

Study Record Updates

Last Update Posted (Actual)

July 8, 2021

Last Update Submitted That Met QC Criteria

June 17, 2021

Last Verified

June 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 12853
  • PBMTC ONC-032P (Other Identifier: Pediatric Blood and Marrow Tranplant Consortium)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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