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

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ClinicalTrials.gov Identifier: NCT03572530
Recruitment Status : Recruiting
First Posted : June 28, 2018
Last Update Posted : March 5, 2019
Sponsor:
Information provided by (Responsible Party):
David Ilan Sandberg, The University of Texas Health Science Center, Houston

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.

Condition or disease Intervention/treatment Phase
Recurrent Ependymoma Drug: 5-Azacytidine (5-AZA) group 1 Drug: 5-Azacytidine (5-AZA) group 2 Drug: 5-Azacytidine (5-AZA) group 3 Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 9 participants
Allocation: Non-Randomized
Intervention Model: Parallel 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 and Adults With Recurrent Posterior Fossa Ependymoma: A Phase I Study
Actual Study Start Date : February 8, 2019
Estimated Primary Completion Date : July 1, 2020
Estimated Study Completion Date : July 1, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Azacitidine

Arm Intervention/treatment
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 (20 mg) into the fourth ventricle. Patients in Group 1 will receive two 5-AZA infusions every week.
Drug: 5-Azacytidine (5-AZA) group 1

5-AZA (20 mg) will be prepared in preservative-free normal saline to a total volume of 1ml. 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.

Other Name: Vidaza

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 (20 mg) into the fourth ventricle. Patients in Group 2 will receive three 5-AZA infusions every week.
Drug: 5-Azacytidine (5-AZA) group 2

5-AZA (20 mg) will be prepared in preservative-free normal saline to a total volume of 1ml. 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.

Other Name: Vidaza

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 (20 mg) into the fourth ventricle. Patients in Group 3 will receive four 5-AZA infusions every week.
Drug: 5-Azacytidine (5-AZA) group 3

5-AZA (20 mg) will be prepared in preservative-free normal saline to a total volume of 1ml. 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.

Other Name: Vidaza




Primary Outcome Measures :
  1. Number of participants who experienced dose-limiting toxicity (DLT) [ Time Frame: 8 weeks ]

    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 :
  1. Number of participants with disease progression as assessed by magnetic resonance imaging (MRI) [ Time Frame: 1 day after surgery to remove tumor (which is about 1 week before the first infusion) ]

    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.


  2. Number of participants with disease progression as assessed by magnetic resonance imaging (MRI) [ Time Frame: 8 weeks after first infusion ]

    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.




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Ages Eligible for Study:   1 Year to 80 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

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): NCT03572530


Contacts
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Contact: Bangning Yu, MD, PhD 713-500-7363 Bangning.Yu@uth.tmc.edu
Contact: David I Sandberg, MD 713-500-7370 David.I.Sandberg@uth.tmc.edu

Locations
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United States, Texas
The University of Texas Health Science Center at Houston Recruiting
Houston, Texas, United States, 77030
Contact: Bangning Yu, MD, PhD    713-500-7363    Bangning.Yu@uth.tmc.edu   
Contact: David I Sandberg, MD    713-500-7370    David.I.Sandberg@uth.tmc.edu   
Sponsors and Collaborators
The University of Texas Health Science Center, Houston
Investigators
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Principal Investigator: David I Sandberg, MD The University of Texas Health Science Center, Houston

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Responsible Party: David Ilan Sandberg, Professor, The University of Texas Health Science Center, Houston
ClinicalTrials.gov Identifier: NCT03572530     History of Changes
Other Study ID Numbers: HSC-MS-18-0309
First Posted: June 28, 2018    Key Record Dates
Last Update Posted: March 5, 2019
Last Verified: March 2019

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

Additional relevant MeSH terms:
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Ependymoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Azacitidine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors