Combination Intraventricular Chemotherapy Pilot Study: 5-... | NCT04958486

NCT04958486

Status Module

Description Module

Arms/Interventions Module

Label	Type	Description	Intervention Names
Treatment	Experimental		Drug: 5-Azacytidine and trastuzumab infusion

Interventions

Name	Type	Description	Arm Group Labels	Other Names
5-Azacytidine and trastuzumab infusion	Drug	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

Outcomes Module

Primary Outcomes

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 Outcomes

Measure	Description	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)

Eligibility Module

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.
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

ID	Term
D001372	Aza Compounds
D009930	Organic Chemicals
D003562	Cytidine
D011741	Pyrimidine Nucleosides
D011743	Pyrimidines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D009705	Nucleosides
D009706	Nucleic Acids, Nucleotides, and Nucleosides
D012263	Ribonucleosides