Combination Intraventricular Chemotherapy Pilot Study: 5-Azacytidine (5-AZA) and Trastuzumab Infusions Into the Fourth Ventricle or Resection Cavity in Children and Adults With Recurrent or Residual Posterior Fossa Ependymoma

The purpose of this study is to establish the safety and tolerability of simultaneous infusions of 5-Azacytidine and trastuzumab into the fourth ventricle of the brain or resection cavity in patients with recurrent posterior fossa ependymoma and to assess the antitumor activity of simultaneous infusions of 5-Azacytidine and trastuzumab into the fourth ventricle of the brain or resection cavity in patients based upon imaging studies and lumbar cerebrospinal fluid (CSF) cytology.

Study Overview

• Status: Recruiting
• Conditions: Fossa Ependymoma
• Intervention / Treatment: Drug: 5-Azacytidine and trastuzumab infusion

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: David I Sandberg, MD; Phone Number: (713) 500-7370; Email: David.I.Sandberg@uth.tmc.edu
• Study Contact Backup: Name: Bangning yu; Phone Number: (713) 500-7363; Email: Bangning.Yu@uth.tmc.edu

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • The University of Texas Health Science Center at Houston
      • Contact: David I Sandberg, MD; Phone Number: 713-500-7370; Email: David.I.Sandberg@uth.tmc.edu
      • Contact: Bangning yu; Phone Number: (713) 500-7363; Email: Bangning.Yu@uth.tmc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 80 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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 4 weeks between any prior radiation treatments or bevacizumab infusions and first infusion of 5-azacytidine or trastuzumab infusions. A minimum of 2 weeks between last dose of any other systemic chemotherapy and first infusion of 5-azacytidine or Trastuzumab 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 red blood cell (RBC) transfusions)
• Patient or patient's legal representative, parent(s), or guardian able to provide written informed consent.
• Patient with abnormal cardiac function (Shortening fraction less than 28% on echocardiogram) will need cardiology clearance prior to enrollment
• Normal renal and liver function on basic metabolic panel. Any patients with abnormal blood urea nitrogen (BUN), creatinine, alanine aminotransferase(AST) or aspartate aminotransferase (ALT) levels will need nephrology and/or gastroenterology clearance prior to enrollment

Exclusion Criteria:

• Enrolled in another treatment protocol
• Patients with disease that is completely resectable
• Has received another investigational or chemotherapy agent within 2 weeks or radiation therapy within 4 weeks prior to 5-azacytidine or trastuzumab infusion into the fourth ventricle
• Patients with any cardiac issues who are not cleared by cardiology for participation in the study
• Evidence of untreated infection
• Pregnant or lactating women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment

Drug: 5-Azacytidine and trastuzumab infusion; Patients will receive once weekly 10 mg intraventricular 5-Azacytidine infusions for six consecutive weeks followed by observation in the infusion suite for a minimum of 30 minutes and once weekly 21 mg intraventricular trastuzumab infusions for six consecutive weeks followed by observation for a minimum of 2 hour after each infusion for the first 2 infusions. During this monitoring period, temperature, blood pressure, heart rate, and oxygen saturation will be measured. Patients will also have a neurological examination performed to observe for neurological changes. All patients will undergo an MRI of the brain and total spine with and without gadolinium within 7 days after the final 5-AZA and trastuzumab infusion to determine treatment response and to assess for any signal changes in the brain or spine caused by the infusions and they will have a 30 day and a 90 day follow-up assessment by telephone or in person for assessment of outcome measures and safety

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with new neurological deficits	A new neurological deficit will be defined as new cranial neuropathy, change in level of consciousness, motor weakness, gait change or cerebellar finding (ataxia, dysmetria, dysdiadochokinesis) that is attributed by treating physicians to infusions. New neurological deficits graded as Grade 3 or higher after infusions will be defined as serious adverse events (SAE's)	7 days after treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in disease progression as assessed by magnetic resonance imaging (MRI)	Baseline(before start of treatment),end of treatment (7 days after treatment)
Change in disease progression as assessed by lumbar CSF cytology	Baseline(before start of treatment),end of treatment (7 days after treatment)

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center, Houston
• Investigators: Principal Investigator: David I Sandberg, MD, The University of Texas Health Science Center, Houston

Study record dates

Study Major Dates

• Study Start (Actual): July 8, 2021
• Primary Completion (Estimated): December 29, 2025
• Study Completion (Estimated): December 29, 2025

Study Registration Dates

• First Submitted: July 1, 2021
• First Submitted That Met QC Criteria: July 1, 2021
• First Posted (Actual): July 12, 2021

Study Record Updates

• Last Update Posted (Actual): May 8, 2024
• Last Update Submitted That Met QC Criteria: May 6, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Trastuzumab; 5-Azacytidine
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Ependymoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Antineoplastic Agents, Immunological; Trastuzumab; Azacitidine
• Other Study ID Numbers: HSC-MS-21-0231

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No