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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	1 Year - 80 Years
Gender	All

More Inclusion & Exclusion 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

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT03572530
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 1
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	The University of Texas Health Science Center, Houston
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	David I Sandberg, MD
Principal Investigator Affiliation	The University of Texas Health Science Center, Houston
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Recruiting
Countries	United States
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Recurrent Ependymoma

Arms & Interventions

Arms

Experimental: 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.

Experimental: 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.

Experimental: 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.

Interventions

Drug: - 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.

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.

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.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Houston, Texas

Status

Recruiting

Address

The University of Texas Health Science Center at Houston

Houston, Texas, 77030

Site Contact

Bangning Yu, MD, PhD

[email protected]

713-500-7363

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