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 System (UT)

Status and phase

Completed

Early Phase 1

Conditions

Fossa Ependymoma

Treatments

Drug: 5-Azacytidine and trastuzumab infusion

Study type

Interventional

Funder types

Other

Identifiers

NCT04958486

HSC-MS-21-0231

Details and patient eligibility

About

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.

Enrollment

4 patients

Sex

All

Ages

1 to 80 years old

Volunteers

No Healthy Volunteers

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