Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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 safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04958486
Recruitment Status : Recruiting
First Posted : July 12, 2021
Last Update Posted : August 5, 2021
Sponsor:
Information provided by (Responsible Party):
David Ilan Sandberg, The University of Texas Health Science Center, Houston

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.

Condition or disease Intervention/treatment Phase
Fossa Ependymoma Drug: 5-Azacytidine and trastuzumab infusion Early Phase 1

Layout table for study information
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

Resource links provided by the National Library of Medicine


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




Primary Outcome Measures :
  1. 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 Outcome Measures :
  1. 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) ]
  2. Change in disease progression as assessed by lumbar CSF cytology [ Time Frame: Baseline(before start of treatment),end of treatment (7 days after treatment) ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

Information from the National Library of Medicine

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


Contacts
Layout table for location contacts
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

Locations
Layout table for location information
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   
Sponsors and Collaborators
The University of Texas Health Science Center, Houston
Investigators
Layout table for investigator information
Principal Investigator: David I Sandberg, MD The University of Texas Health Science Center, Houston
Layout table for additonal information
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: August 5, 2021
Last Verified: August 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by David Ilan Sandberg, The University of Texas Health Science Center, Houston:
5-Azacytidine
Trastuzumab
Additional relevant MeSH terms:
Layout table for MeSH terms
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