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 University of Texas Health Science Center, Houston1 site in 1 country4 target enrollmentJuly 8, 2021

ConditionsFossa Ependymoma

Interventions5-Azacytidine and trastuzumab infusion

Drugs5-Azacytidine and trastuzumab infusion

Overview

Phase: Early Phase 1
Intervention: 5-Azacytidine and trastuzumab infusion
Conditions: Fossa Ependymoma
Sponsor: The University of Texas Health Science Center, Houston
Enrollment: 4
Locations: 1
Primary Endpoint: Number of patients with new neurological deficits
Status: Completed
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

July 8, 2021

End Date

September 29, 2023

Last Updated

last year

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

The University of Texas Health Science Center, Houston

Responsible Party

Principal Investigator

David Ilan Sandberg

Professor

The University of Texas Health Science Center, Houston

Eligibility Criteria

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.

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

Arms & Interventions

Treatment

Intervention: 5-Azacytidine and trastuzumab infusion

Outcomes

Primary Outcomes

Number of patients with new neurological deficits

Time Frame: 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 Outcomes

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))