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Methotrexate and Etoposide Infusions Into the Fourth Ventricle in Children With Recurrent Posterior Fossa Brain Tumors

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ClinicalTrials.gov Identifier: NCT02905110
Recruitment Status : Recruiting
First Posted : September 19, 2016
Last Update Posted : June 25, 2019
Sponsor:
Information provided by (Responsible Party):
David Ilan Sandberg, The University of Texas Health Science Center, Houston

Brief Summary:
The goal of this clinical research study is to establish the safety of simultaneous infusions of methotrexate and etoposide into the fourth ventricle of the brain or resection cavity in patients with recurrent malignant posterior fossa brain tumors. These tumors include medulloblastoma, ependymoma, atypical teratoid/rhabdoid tumor or other malignant brain tumor with recurrence or progression involving anywhere in the brain and/or spine. Patients' disease must have originated in the posterior fossa of the brain.

Condition or disease Intervention/treatment Phase
Brain Tumor Recurrent Drug: Methotrexate Drug: Etoposide Procedure: Ommaya Reservoir Early Phase 1

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Detailed Description:

If the participant is eligible to take part in this study, the participant will have surgery to place a catheter into the Ommaya reservoir. The Ommaya reservoir is a catheter system that allows drugs to be administered directly to parts of the brain. This catheter will be used for the infusion of methotrexate and etoposide directly into the 4th ventricle of the brain, which is 1 of the 4 connected fluid-filled cavities in the brain.

If the study doctor thinks it is necessary, based on the location of the tumor, the tumor may also be removed while the participant is already under anesthesia just before the catheter is placed.

Study Drug Administration:

The participant will receive twice weekly 4 mg intraventricular methotrexate infusions for six consecutive weeks and daily 1 mg intraventricular etoposide infusion five times per week, every 2 weeks. Etoposide will be administered on weeks 1, 3, and 5.

Methotrexate and Etoposide will be infused though the ommaya reservoir catheter directly into the 4th ventricle of the brain starting at a minimum of 7 days after the catheter placement surgery. A MRI will be done to confirm adequate cerebrospinal fluid flow. The etoposide infusion will last 3-4 minutes and the methotrexate infusion will last 3 minutes.

If the participant already has an Ommaya catheter, methotrexate and etoposide will begin after an MRI has confirmed adequate cerebrospinal fluid flow.

Study Visits:

Prior to first infusion:

Medical history will be reviewed and any updates to health will be recorded. Physical and Neurological exam with vital signs will be done. Blood (about 1 teaspoon) will be drawn for routine test. A lumbar puncture will be done. A MRI scan of the brain and spine will be done to check the status of the disease.

On the days of the Methotrexate and Etoposide Infusion:

A neurological exam with vital signs will be done. A Ommaya reservoir tap (a catheter is placed into the Ommaya reservoir to give the methotrexate and etoposide infusion.

Cerebrospinal fluid (about 1 teaspoon) will be collected for routine tests.

Within 7 days of completing the Final infusion:

A neurological exam with vital signs will be done. A lumbar puncture and lab work will be done. A MRI scan of the brain and spine will be done to check status of the disease.

Length of Study:

The participant will receive 12 infusions of Methotrexate 4 mg and 15 infusions of Etoposide 1 mg, as long as the doctor thinks it is in their best interest. The participant will no longer be able to receive the study drug if the disease gets worse, if intolerable side effects occur, or if unable to follow study directions.

This is an investigation study. Methotrexate is FDA approved and commercially available for infusion directly into brain tumors. The infusion of methotrexate into the 4th ventricle of the brain in investigational. Etoposide is FDA approved and commercially available to be given by mouth or into the bloodstream (intravenously) but has never been given in the 4th ventricle of the brain. The infusion of methotrexate and etoposide into the 4th ventricle of the brain is investigational.

Up to 10 patients will be enrolled in this study. All will be enrolled at Children's Memorial Hermann Hospital.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Combination Intraventricular Chemotherapy Pilot Study: Methotrexate and Etoposide Infusions Into the Fourth Ventricle or Resection Cavity in Children With Recurrent Posterior Fossa Brain Tumors
Study Start Date : October 2016
Estimated Primary Completion Date : November 2020
Estimated Study Completion Date : November 2020


Arm Intervention/treatment
Experimental: Methotrexate / Etoposide Infusion
12 infusions of intraventricular Methotrexate and 15 infusions of intraventricular Etoposide into implanted fourth ventricle catheter/Ommaya reservoir following surgical catheter placement into fourth ventricle. Methotrexate will be infused twice weekly for 6 weeks and etoposide will be infused 5 times a week on weeks 1, 3 , and 5.
Drug: Methotrexate
Methotrexate 4 mg into fourth ventricle of the brain via the Ommaya Reservoir 2 days a week for 6 weeks. Each patient will have 12 infusions.
Other Name: Trexall, Rasuvo

Drug: Etoposide
Etoposide 1 mg into fourth ventricle of the brain via the Ommaya Reservoir 5 days a week for weeks 1, 3, and 5. Each patient will have 15 infusions.
Other Name: VePesid, Toposar, Etopophos

Procedure: Ommaya Reservoir
Surgical catheter placement into the fourth ventricle of the brain




Primary Outcome Measures :
  1. Number of patients with grade 3 through grade 5 new neurological adverse events that are related to study drug, graded according to NCI CTCAE Version 4.0 [ Time Frame: 4 months ]
    New neurological deficit defined as new cranial neuropathy, nystagmus, change in mental status, motor deficit or cerebellar finding (ataxia, dysmetria, dysdiadochokinesis) that is attributed by treating physicians to intraventricular methotrexate and etoposide infusions. Primary endpoint for basis of safety monitoring is acute toxicity occurring at any time within 30 days of receiving the intraventricular methotrexate and etoposide infusion. Rate of acute toxicity monitored using Bayesian method of Thall and Sung. Method of Kaplan and Meier used to estimate unadjusted distributions of time to a neurological deficit and progression free survival time and summary statistic of all variable computed and tabulated



Information from the National Library of Medicine

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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
Criteria

Inclusion Criteria:

  • Age 1 - 80 years at time of recurrence or progression
  • Diagnosis: Patients with histologically verified medulloblastoma, ependymoma, or atypical teratoid/rhabdoid tumor or other malignant brain tumor with recurrence or progression involving anywhere in the brain and/or spine. 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 an Ommaya reservoir or agreement to have one placed.
  • A minimum of 7 days between last dose of systemic chemotherapy and/or radiation therapy and first infusion of chemotherapy into fourth ventricle
  • Life expectancy of at least 12 weeks in the opinion of the PI
  • 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 transfusions)
  • Patient or patient's legal representative, parent(s), or guardian able to provide written informed consent.

Exclusion Criteria:

  • Enrolled in another treatment protocol
  • Has received another investigational or chemotherapy agent or radiation therapy within 7 days prior to intraventricular chemotherapy infusions
  • 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): NCT02905110


Contacts
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Contact: Bangning L Yu, RN, PhD 713 500-7363 Bangning.Yu@uth.tmc.edu
Contact: David Sandberg, MD 713 500-7410 David.I.Sandberg@uth.tmc.edu

Locations
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United States, Texas
UTHealth & Children's Memorial Hermann Hospital Recruiting
Houston, Texas, United States, 77030
Contact: David Sandberg, M.D.    713-500-7410    David.I.Sandberg@uth.tmc.edu   
Contact: Bangning Yu, R.N., PhD    713 500-7363    Bangning.Yu@uth.tmc.edu   
Sponsors and Collaborators
The University of Texas Health Science Center, Houston
Investigators
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Principal Investigator: David Sandberg, MD UTHealth

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Responsible Party: David Ilan Sandberg, Director of Pediatric Neurosurgery, Associate Professor Pediatric Surgery and Neurosurgery, The University of Texas Health Science Center, Houston
ClinicalTrials.gov Identifier: NCT02905110     History of Changes
Other Study ID Numbers: HSC-MS-16-0639
First Posted: September 19, 2016    Key Record Dates
Last Update Posted: June 25, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by David Ilan Sandberg, The University of Texas Health Science Center, Houston:
Malignant Neoplasms, Brain
medulloblastoma
ependymoma
Atypical Teratoid Rhabdoid Tumor (ATRT)
Additional relevant MeSH terms:
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Brain Neoplasms
Neoplasms
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Methotrexate
Etoposide
Etoposide phosphate
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors