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
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ClinicalTrials.gov Identifier: NCT04958486 |
Recruitment Status :
Recruiting
First Posted : July 12, 2021
Last Update Posted : July 1, 2022
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Fossa Ependymoma | Drug: 5-Azacytidine and trastuzumab infusion | Early Phase 1 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 10 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official 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 |
Actual Study Start Date : | July 8, 2021 |
Estimated Primary Completion Date : | July 5, 2023 |
Estimated Study Completion Date : | July 5, 2023 |

Arm | Intervention/treatment |
---|---|
Experimental: Treatment |
Drug: 5-Azacytidine and trastuzumab infusion
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 |
- 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)
- 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) ]
- Change in disease progression as assessed by lumbar CSF cytology [ Time Frame: Baseline(before start of treatment),end of treatment (7 days after treatment) ]

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Ages Eligible for Study: | 1 Year to 80 Years (Child, Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04958486
Contact: David I Sandberg, MD | (713) 500-7370 | David.I.Sandberg@uth.tmc.edu | |
Contact: Bangning Yu | (713) 500-7363 | Bangning.Yu@uth.tmc.edu |
United States, Texas | |
The University of Texas Health Science Center at Houston | Recruiting |
Houston, Texas, United States, 77030 | |
Contact: David I Sandberg, MD 713-500-7370 David.I.Sandberg@uth.tmc.edu | |
Contact: Bangning Yu (713) 500-7363 Bangning.Yu@uth.tmc.edu |
Principal Investigator: | David I Sandberg, MD | The University of Texas Health Science Center, Houston |
Responsible Party: | David Ilan Sandberg, Professor, The University of Texas Health Science Center, Houston |
ClinicalTrials.gov Identifier: | NCT04958486 |
Other Study ID Numbers: |
HSC-MS-21-0231 |
First Posted: | July 12, 2021 Key Record Dates |
Last Update Posted: | July 1, 2022 |
Last Verified: | June 2022 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
5-Azacytidine Trastuzumab |
Ependymoma Glioma Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue |
Trastuzumab Azacitidine Antineoplastic Agents, Immunological Antineoplastic Agents Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Enzyme Inhibitors |