Infusion of 5-Azacytidine (5-AZA) Into the Fourth Ventricle in Children With Recurrent Posterior Fossa Ependymoma (5-AZA)

November 28, 2018 updated by: David Ilan Sandberg, The University of Texas Health Science Center, Houston

Infusion of 5-Azacytidine (5-AZA) Into the Fourth Ventricle or Resection Cavity in Children With Recurrent Posterior Fossa Ependymoma: A Pilot Study

The goal of this clinical research study is to establish the safety of direct administration of 5-Azacytidine into the fourth ventricle of the brain or resection cavity in patients with recurrent posterior fossa ependymoma.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

If the participant is eligible to take part in this study, the participant will have surgery to place a catheter into the Ommaya reservoir. The Ommaya reservoir is a catheter system that allows drugs to be administered directly to parts of the brain. This catheter will used for the infusion of 5-Azacytidine directly into the 4th ventricle of the brain, which is 1 or the 4 connected fluid-filled cavities in the brain.

If the study doctor thinks it is necessary, based on the location of the tumor, the tumor may also be removed while the participant is already under anesthesia just before the catheter is placed.

Study Drug Administration:

The participant will receive 12 weekly (+/- one day) 10 mg infusions of 5-Azacytidine.

5-Azacytidine will be infused through the Ommaya reservoir catheter directly into the 4th ventricle of the brain starting at a minimum of 7 days after the catheter placement surgery. A MRI will be done to confirm adequate cerebrospinal fluid flow. The 5-Azacytidine infusion will last 2-3 minutes.

If the participant already has an Ommaya catheter, 5-Azacytidine will begin after an MRI has confirmed adequate cerebrospinal fluid flow.

Study Visits:

Prior to first infusion:

Medical history will be reviewed and any updates to health will be recorded. Physical and Neurological exam with vital signs will be done. Blood (about 1 teaspoon) will be drawn for routine test. A lumbar puncture will be done. A MRI scan of the brain and spine will be done to check the status of the disease.

On the days of the 5-Azacytidine Infusion:

A neurological exam with vital signs will be done. A Ommaya reservoir tap (a catheter is placed into the Ommaya reservoir to give the 5-Azacytidine infusion.

Cerebrospinal fluid (about 1 teaspoon) will be collected for routine tests.

Within 7 days of completing the Final infusion:

A neurological exam with vital signs will be done. A lumbar puncture will be done. A MRI scan of the brain and spine will be done to check status of the disease.

Length of Study:

The participant will receive 12 infusions of 5-Azacytidine, as long as the doctor thinks it is in their best interest. The participant will no longer be able to receive the study drug if the disease gets worse, if intolerable side effects occur, or if unable to follow study directions.

This is an investigation study. 5-Azacytidine is FDA approved and commercially available to be given subcutaneous or into the bloodstream (intravenously) but has never been given in the 4th ventricle of the brain. The infusion of 5-Azacytidine into the 4th ventricle of the brain is investigational.

Up to 10 patients will be enrolled in this study. All will be enrolled at Children's Memorial Hermann Hospital

Study Type

Interventional

Enrollment (Actual)

6

Phase

  • Early Phase 1

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

  • United States
    • Texas
      • Houston, Texas, United States, 77030
        • UTHealth & Children's Memorial Hermann Hospital

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

1 year to 21 years (ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Diagnosis: Patients with histologically verified ependymoma, with recurrence or progression involving anywhere in the brain and/or spine. To be eligible, patients' disease must have originated in the posterior fossa of the brain.
  • Patient must have either measurable or evaluable tumor as assessed by MRI of the brain and total spine.
  • An implanted catheter in the fourth ventricle or posterior fossa tumor cavity attached to a ventricular access device or agreement to have one placed.
  • A minimum of 7 days between last dose of systemic chemotherapy and/or radiation therapy and first infusion of 5-Azacytidine into fourth ventricle.
  • Life expectancy of at least 12 weeks in the opinion of the PI
  • Lansky score of 50 or greater if ≤16 years of age or Karnofsky score of 50 or greater if > 16 years of age.
  • Existing neurological deficits must have been stable for a minimum of 1 week prior to study enrollment.
  • Patients must have recovered from the acute toxic effects of all prior anticancer chemotherapy
  • Adequate bone marrow function defined by peripheral absolute neutrophil count (ANC) ≥ 500/µL, platelet count ≥ 50,000/ µL (transfusion independent), and hemoglobin ≥9.0 gm/dL (may receive RBC transfusions)
  • Patient or patient's legal representative, parent(s), or guardian able to provide written informed consent.

Exclusion Criteria:

  • Enrolled in another treatment protocol
  • Has received another investigational or chemotherapy agent or radiation therapy within 7 days prior to 5-Azacytidine infusion into the fourth ventricle.
  • Evidence of untreated infection
  • Pregnant of lactating women

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: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: 5-Azacytidine Infusion
12 infusions (once a week) into implanted fourth ventricle catheter/Ommaya reservoir following surgical catheter placement into fourth ventricle.
Drug: 5-Azacytidine
5-Azacytidine 10 mg into the fourth ventricle of the brain via the Ommaya reservoir 1 day a week for 12 weeks.
Other Names:
  • Vidaza, Mylosar

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of patients with grade 3 through grade 5 new neurological adverse events that are related to study drug, graded according to NCI CTCAE Version 4.0
Time Frame: 4 months
New neurological deficit defined as new cranial neuropathy, nystagmus, change in mental status, motor deficit or cerebellar finding (ataxia, dysmetria, dysdiadochokinesis) that is attributed by treating physicians to intraventricular 5-Azacytidine infusions. Primary endpoint for basis of safety monitoring is acute toxicity occurring at any time within 30 days of receiving the intraventricular 5-Azacytidine infusion. Rate of acute toxicity monitored using Bayesian method of Thall and Sung. Method of Kaplan and Meier used to estimate unadjusted distributions o time to a neurological deficit and progression free survival time and summary statistic of all variable computed and tabulated.
4 months

Collaborators and Investigators

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

Sponsor

The University of Texas Health Science Center, Houston

Investigators

  • Principal Investigator: David I Sandberg, M.D., UTHealth

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

February 1, 2017

Primary Completion (ACTUAL)

November 28, 2018

Study Completion (ACTUAL)

November 28, 2018

Study Registration Dates

First Submitted

October 18, 2016

First Submitted That Met QC Criteria

October 20, 2016

First Posted (ESTIMATE)

October 21, 2016

Study Record Updates

Last Update Posted (ACTUAL)

November 30, 2018

Last Update Submitted That Met QC Criteria

November 28, 2018

Last Verified

November 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HSC-MS-16-0739

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

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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