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

NCT02940483 | Completed Early Phase 1 DMC FDA Drug

• 1 other identifier: HSC-MS-16-0739
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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.

Conditions

Brain Tumor Recurrent

Keywords

Ependymoma

Outcome Measures

Primary Outcomes (1)

• 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

  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

Study Arms (1)

5-Azacytidine Infusion

EXPERIMENTAL

12 infusions (once a week) into implanted fourth ventricle catheter/Ommaya reservoir following surgical catheter placement into fourth ventricle.

Drug: 5-Azacytidine

Interventions

5-Azacytidine DRUG

5-Azacytidine 10 mg into the fourth ventricle of the brain via the Ommaya reservoir 1 day a week for 12 weeks.

Also known as: Vidaza, Mylosar

5-Azacytidine Infusion

Eligibility Criteria

• Age: 1 Year - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• The University of Texas Health Science Center, Houston: lead

Study Sites (1)

UTHealth & Children's Memorial Hermann Hospital

Houston, Texas, 77030, United States

Location

Related Publications (1)

• 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.

  PMID: 34171339 DERIVED

MeSH Terms

Conditions

Brain Neoplasms; Ependymoma

Interventions

Azacitidine

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• David I Sandberg, M.D.

  UTHealth

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Pediatric Neurosurgery, Professor Pediatric Surgery and Neurosurgery

Study Record Dates

• First Submitted: October 18, 2016
• First Posted: October 21, 2016
• Study Start: February 1, 2017
• Primary Completion: November 28, 2018
• Study Completion: November 28, 2018
• Last Updated: November 30, 2018

Record last verified: 2018-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)