search
Back to results

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

Primary Purpose

Recurrent Ependymoma

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
5-Azacytidine (5-AZA) group 1
5-Azacytidine (5-AZA) group 2
5-Azacytidine (5-AZA) group 3
Sponsored by
The University of Texas Health Science Center, Houston
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recurrent Ependymoma

Eligibility Criteria

1 Year - 80 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • The University of Texas Health Science Center at HoustonRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

group 1

group 2

group 3

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

Number of participants who experienced dose-limiting toxicity (DLT)
Dose-limiting toxicity will be defined as any of the following events: New neurological deficit (grade 3 or higher) probably or definitely attributed to intraventricular 5-azacytidine infusions. New adverse event involving any organ probably or definitely attributed to intraventricular 5-azacytidine infusions with the specific exclusion of: Grade 3 or higher nausea and vomiting < 3 days duration and grade 3 or higher headache < 3 days duration.

Secondary Outcome Measures

Number of participants with disease progression as assessed by magnetic resonance imaging (MRI)
The PI and radiologist will determine Response to treatment according to the following three categories. Disease progression corresponds with the "Progressive Disease" category. Complete Response (CR): Disappearance of all non-target lesions. Stable Disease (SD) / Incomplete Response (IR): The persistence of one or more non-target lesions. Progressive Disease (PD): The appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
Number of participants with disease progression as assessed by magnetic resonance imaging (MRI)
The PI and radiologist will determine Response to treatment according to the following three categories. Disease progression corresponds with the "Progressive Disease" category. Complete Response (CR): Disappearance of all non-target lesions. Stable Disease (SD) / Incomplete Response (IR): The persistence of one or more non-target lesions. Progressive Disease (PD): The appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.

Full Information

First Posted
June 19, 2018
Last Updated
June 20, 2023
Sponsor
The University of Texas Health Science Center, Houston
search

1. Study Identification

Unique Protocol Identification Number
NCT03572530
Brief Title
Infusion of 5-Azacytidine (5-AZA) Into the Fourth Ventricle in Patients With Recurrent Posterior Fossa Ependymoma
Acronym
5-AZA
Official Title
Infusion of 5-Azacytidine (5-AZA) Into the Fourth Ventricle or Resection Cavity in Children and Adults With Recurrent Posterior Fossa Ependymoma: A Phase I Study
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 8, 2019 (Actual)
Primary Completion Date
December 1, 2025 (Anticipated)
Study Completion Date
December 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The University of Texas Health Science Center, Houston

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Ependymoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
9 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
group 1
Arm Type
Experimental
Arm Description
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.
Arm Title
group 2
Arm Type
Experimental
Arm Description
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.
Arm Title
group 3
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
5-Azacytidine (5-AZA) group 1
Other Intervention Name(s)
Vidaza
Intervention Description
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
Intervention Name(s)
5-Azacytidine (5-AZA) group 2
Other Intervention Name(s)
Vidaza
Intervention Description
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
Intervention Name(s)
5-Azacytidine (5-AZA) group 3
Other Intervention Name(s)
Vidaza
Intervention Description
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.
Primary Outcome Measure Information:
Title
Number of participants who experienced dose-limiting toxicity (DLT)
Description
Dose-limiting toxicity will be defined as any of the following events: New neurological deficit (grade 3 or higher) probably or definitely attributed to intraventricular 5-azacytidine infusions. New adverse event involving any organ probably or definitely attributed to intraventricular 5-azacytidine infusions with the specific exclusion of: Grade 3 or higher nausea and vomiting < 3 days duration and grade 3 or higher headache < 3 days duration.
Time Frame
8 weeks
Secondary Outcome Measure Information:
Title
Number of participants with disease progression as assessed by magnetic resonance imaging (MRI)
Description
The PI and radiologist will determine Response to treatment according to the following three categories. Disease progression corresponds with the "Progressive Disease" category. Complete Response (CR): Disappearance of all non-target lesions. Stable Disease (SD) / Incomplete Response (IR): The persistence of one or more non-target lesions. Progressive Disease (PD): The appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
Time Frame
1 day after surgery to remove tumor (which is about 1 week before the first infusion)
Title
Number of participants with disease progression as assessed by magnetic resonance imaging (MRI)
Description
The PI and radiologist will determine Response to treatment according to the following three categories. Disease progression corresponds with the "Progressive Disease" category. Complete Response (CR): Disappearance of all non-target lesions. Stable Disease (SD) / Incomplete Response (IR): The persistence of one or more non-target lesions. Progressive Disease (PD): The appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
Time Frame
8 weeks after first infusion

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Bangning Yu, MD, PhD
Phone
713-500-7363
Email
Bangning.Yu@uth.tmc.edu
First Name & Middle Initial & Last Name or Official Title & Degree
David I Sandberg, MD
Phone
713-500-7370
Email
David.I.Sandberg@uth.tmc.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David I Sandberg, MD
Organizational Affiliation
The University of Texas Health Science Center, Houston
Official's Role
Principal Investigator
Facility Information:
Facility Name
The University of Texas Health Science Center at Houston
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bangning Yu, MD, PhD
Phone
713-500-7363
Email
Bangning.Yu@uth.tmc.edu
First Name & Middle Initial & Last Name & Degree
David I Sandberg, MD
Phone
713-500-7370
Email
David.I.Sandberg@uth.tmc.edu

12. IPD Sharing Statement

Citations:
PubMed Identifier
34171339
Citation
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.
Results Reference
derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs