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

Early Phase 1

Completed

• Conditions: Fossa Ependymoma
• Interventions: Drug: 5-Azacytidine and trastuzumab infusion

• Registration Number: NCT04958486
• Lead Sponsor: The University of Texas Health Science Center, Houston

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-07-01
• Study First Submitted QC: 2021-07-01
• Study Start: 2021-07-08
• Study First Posted: 2021-07-12
• Primary Completion: 2023-09-29
• Study Completion: 2023-09-29
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-26
• Last Update Posted: 2025-03-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 4

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment	5-Azacytidine and trastuzumab infusion	-

Primary Outcome Measures

Name	Time	Method
Number of patients with new neurological deficits	7 days after treatment	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)

Secondary Outcome Measures

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

Trial Locations

Locations (1)

The University of Texas Health Science Center at Houston; 🇺🇸 Houston, Texas, United States