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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

Primary Purpose

Fossa Ependymoma

Status

Recruiting

Phase

Early Phase 1

Locations

United States

Study Type

Interventional

Intervention

5-Azacytidine and trastuzumab infusion

About this trial

This is an interventional treatment trial for Fossa Ependymoma focused on measuring 5-Azacytidine, Trastuzumab

Eligibility Criteria

1 Year - 80 Years (Child, Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

The University of Texas Health Science Center at HoustonRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment

Arm Description

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

Change in disease progression as assessed by magnetic resonance imaging (MRI)

Change in disease progression as assessed by lumbar CSF cytology

Full Information

NCT ID

NCT04958486

First Posted

July 1, 2021

Last Updated

June 20, 2023

Sponsor

The University of Texas Health Science Center, Houston

1. Study Identification

Unique Protocol Identification Number

NCT04958486

Brief Title

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

Official Title

Study Type

Interventional

2. Study Status

Record Verification Date

June 2023

Overall Recruitment Status

Recruiting

Study Start Date

July 8, 2021 (Actual)

Primary Completion Date

July 5, 2025 (Anticipated)

Study Completion Date

July 5, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

The University of Texas Health Science Center, Houston

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Fossa Ependymoma

Keywords

5-Azacytidine, Trastuzumab

7. Study Design

Primary Purpose

Treatment

Study Phase

Early Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Treatment

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

5-Azacytidine and trastuzumab infusion

Intervention Description

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

Primary Outcome Measure Information:

Title

Number of patients with new neurological deficits

Description

Time Frame

7 days after treatment

Secondary Outcome Measure Information:

Title

Change in disease progression as assessed by magnetic resonance imaging (MRI)

Time Frame

Baseline(before start of treatment),end of treatment (7 days after treatment)

Title

Change in disease progression as assessed by lumbar CSF cytology

Time Frame

Baseline(before start of treatment),end of treatment (7 days after treatment)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

1 Year

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

David I Sandberg, MD

Phone

(713) 500-7370

David.I.Sandberg@uth.tmc.edu

First Name & Middle Initial & Last Name or Official Title & Degree

Bangning Yu

Phone

(713) 500-7363

Bangning.Yu@uth.tmc.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

David I Sandberg, MD

Organizational Affiliation

The University of Texas Health Science Center, Houston

Official's Role

Principal Investigator

Facility Information:

Facility Name

The University of Texas Health Science Center at Houston

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

David I Sandberg, MD

Phone

713-500-7370

David.I.Sandberg@uth.tmc.edu

First Name & Middle Initial & Last Name & Degree

Bangning Yu

Phone

(713) 500-7363

Bangning.Yu@uth.tmc.edu

12. IPD Sharing Statement

Plan to Share IPD

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