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

NCT ID: NCT03572530

Last Updated: 2025-04-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-02-08
• Study Completion Date: 2020-11-24

Brief Summary

This study seeks to determine the optimum dose frequency of 5-Azacytidin (5-AZA) infusions into the fourth ventricle of the brain. The study's primary objective is to establish the maximum tolerated dose for infusions of 5-Azacytidine into the fourth ventricle in patients with recurrent ependymoma. The study's secondary objective is to assess the antitumor activity of 5-Azacytidine infusions into the fourth ventricle based upon imaging studies and cytology.

Conditions

Recurrent Ependymoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

group 1

5-Azacytidine (5-AZA) group 1: Enrolled patients will undergo surgical placement of a ventricular catheter into the fourth ventricle that will be attached to a subcutaneously placed reservoir. Patients will be divided into 3 dose groups and receive 8 weeks of intraventricular 5-AZA (12 mg) into the fourth ventricle. Patients in Group 1 will receive two 5-AZA infusions every week.

Group Type: EXPERIMENTAL

5-Azacytidine (5-AZA) group 1

Intervention Type: DRUG

5-AZA (12 mg) will be prepared in preservative-free normal saline to a total volume of 1.2ml. 5-AZA will be infused over a minimum of 30 seconds. 5-AZA will be followed by a 1 ml preservative-free normal saline flush over a minimum of 30 seconds.

Patients will receive two, three, or four 5-AZA infusions per week depending on the dosing algorithm (see below). We refer to these dosing schedules as dose 1, 2, or 3.

Patients assigned to dose 1 will receive two 5-AZA infusions per week (typically Monday and Thursday but may be given on other days based upon logistical considerations) for 8 consecutive weeks.

group 2

5-Azacytidine (5-AZA) group 2: Enrolled patients will undergo surgical placement of a ventricular catheter into the fourth ventricle that will be attached to a subcutaneously placed reservoir. Patients will be divided into 3 dose groups and receive 8 weeks of intraventricular 5-AZA (12 mg) into the fourth ventricle. Patients in Group 2 will receive three 5-AZA infusions every week.

Group Type: EXPERIMENTAL

5-Azacytidine (5-AZA) group 2

Intervention Type: DRUG

5-AZA (12 mg) will be prepared in preservative-free normal saline to a total volume of 1.2ml. 5-AZA will be infused over a minimum of 30 seconds. 5-AZA will be followed by a 1 ml preservative-free normal saline flush over a minimum of 30 seconds.

Patients will receive two, three, or four 5-AZA infusions per week depending on the dosing algorithm (see below). We refer to these dosing schedules as dose 1, 2, or 3.

Patients assigned to dose 2 will receive three 5-AZA infusions per week (typically Monday, Wednesday, and Friday but may be given on other days based upon logistical considerations) for 8 consecutive weeks.

group 3

5-Azacytidine (5-AZA) group 3: Enrolled patients will undergo surgical placement of a ventricular catheter into the fourth ventricle that will be attached to a subcutaneously placed reservoir. Patients will be divided into 3 dose groups and receive 8 weeks of intraventricular 5-AZA (12 mg) into the fourth ventricle. Patients in Group 3 will receive four 5-AZA infusions every week.

Group Type: EXPERIMENTAL

5-Azacytidine (5-AZA) group 3

Intervention Type: DRUG

5-AZA (12 mg) will be prepared in preservative-free normal saline to a total volume of 1.2ml. 5-AZA will be infused over a minimum of 30 seconds. 5-AZA will be followed by a 1 ml preservative-free normal saline flush over a minimum of 30 seconds.

Patients will receive two, three, or four 5-AZA infusions per week depending on the dosing algorithm (see below). We refer to these dosing schedules as dose 1, 2, or 3.

Patients assigned to dose 3 will receive four 5-AZA infusions per week (on any 4 weekdays based upon logistical considerations) for 8 consecutive weeks.

Interventions

5-Azacytidine (5-AZA) group 1

5-AZA (12 mg) will be prepared in preservative-free normal saline to a total volume of 1.2ml. 5-AZA will be infused over a minimum of 30 seconds. 5-AZA will be followed by a 1 ml preservative-free normal saline flush over a minimum of 30 seconds.

Patients will receive two, three, or four 5-AZA infusions per week depending on the dosing algorithm (see below). We refer to these dosing schedules as dose 1, 2, or 3.

Patients assigned to dose 1 will receive two 5-AZA infusions per week (typically Monday and Thursday but may be given on other days based upon logistical considerations) for 8 consecutive weeks.

Intervention Type: DRUG

5-Azacytidine (5-AZA) group 2

5-AZA (12 mg) will be prepared in preservative-free normal saline to a total volume of 1.2ml. 5-AZA will be infused over a minimum of 30 seconds. 5-AZA will be followed by a 1 ml preservative-free normal saline flush over a minimum of 30 seconds.

Patients will receive two, three, or four 5-AZA infusions per week depending on the dosing algorithm (see below). We refer to these dosing schedules as dose 1, 2, or 3.

Patients assigned to dose 2 will receive three 5-AZA infusions per week (typically Monday, Wednesday, and Friday but may be given on other days based upon logistical considerations) for 8 consecutive weeks.

Intervention Type: DRUG

5-Azacytidine (5-AZA) group 3

5-AZA (12 mg) will be prepared in preservative-free normal saline to a total volume of 1.2ml. 5-AZA will be infused over a minimum of 30 seconds. 5-AZA will be followed by a 1 ml preservative-free normal saline flush over a minimum of 30 seconds.

Patients will receive two, three, or four 5-AZA infusions per week depending on the dosing algorithm (see below). We refer to these dosing schedules as dose 1, 2, or 3.

Patients assigned to dose 3 will receive four 5-AZA infusions per week (on any 4 weekdays based upon logistical considerations) for 8 consecutive weeks.

Intervention Type: DRUG

Other Intervention Names

Vidaza; Vidaza; Vidaza

Eligibility Criteria

Inclusion Criteria

• Diagnosis: Patients with histologically verified ependymoma, with recurrence or progression anywhere in the brain and/or spine. Patients are also eligible if they have refractory disease, which will be defined as residual tumor which has not been completely cleared despite prior treatments. 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-AZA into fourth ventricle
• Life expectancy of at least 12 weeks in the opinion of the principal investigator
• 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-AZA infusion into the fourth ventricle
• Evidence of untreated infection
• Pregnant or lactating women

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The University of Texas Health Science Center, Houston

OTHER

Sponsor Role: lead

Responsible Party

David Ilan Sandberg

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

David I Sandberg, MD

Role: PRINCIPAL_INVESTIGATOR

The University of Texas Health Science Center, Houston

Locations

The University of Texas Health Science Center at Houston

Houston, Texas, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 34171339 (View on PubMed)

Other Identifiers

HSC-MS-18-0309

Identifier Type: -

Identifier Source: org_study_id