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

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ClinicalTrials.gov Identifier: NCT02940483

Recruitment Status : Completed

First Posted : October 21, 2016

Last Update Posted : November 30, 2018

View this study on Beta.ClinicalTrials.gov

Sponsor:

Information provided by (Responsible Party):

David Ilan Sandberg, The University of Texas Health Science Center, Houston

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Brain Tumor Recurrent	Drug: 5-Azacytidine	Early Phase 1

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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 Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	6 participants
Allocation:	N/A
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Infusion of 5-Azacytidine (5-AZA) Into the Fourth Ventricle or Resection Cavity in Children With Recurrent Posterior Fossa Ependymoma: A Pilot Study
Actual Study Start Date :	February 1, 2017
Actual Primary Completion Date :	November 28, 2018
Actual Study Completion Date :	November 28, 2018

Resource links provided by the National Library of Medicine

Drug Information available for: Azacitidine

Genetic and Rare Diseases Information Center resources: Ependymoma Glioma Neuroepithelioma

U.S. FDA Resources

Arms and Interventions

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 Name: Vidaza, Mylosar

Outcome Measures

Primary Outcome Measures :

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.

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	1 Year to 21 Years (Child, Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02940483

Locations

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

Sponsors and Collaborators

The University of Texas Health Science Center, Houston

Investigators

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

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Lang F, Liu Y, Chou FJ, Yang C. Genotoxic therapy and resistance mechanism in gliomas. Pharmacol Ther. 2021 Dec;228:107922. doi: 10.1016/j.pharmthera.2021.107922. Epub 2021 Jun 23.

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Responsible Party:	David Ilan Sandberg, Director of Pediatric Neurosurgery, Professor Pediatric Surgery and Neurosurgery, The University of Texas Health Science Center, Houston
ClinicalTrials.gov Identifier:	NCT02940483
Other Study ID Numbers:	HSC-MS-16-0739
First Posted:	October 21, 2016 Key Record Dates
Last Update Posted:	November 30, 2018
Last Verified:	November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

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Studies a U.S. FDA-regulated Drug Product:	Yes
Studies a U.S. FDA-regulated Device Product:	No

Keywords provided by David Ilan Sandberg, The University of Texas Health Science Center, Houston:


Ependymoma

Additional relevant MeSH terms:

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Ependymoma Recurrence Disease Attributes Pathologic Processes Neoplasms Glioma Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal	Neoplasms by Histologic Type Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Azacitidine Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Enzyme Inhibitors

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