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

NCT02905110 | Completed Early Phase 1 DMC FDA Drug

• 1 other identifier: HSC-MS-16-0639
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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.

Conditions

Brain Tumor Recurrent

Keywords

Malignant Neoplasms, Brain; medulloblastoma; ependymoma; Atypical Teratoid Rhabdoid Tumor (ATRT)

Outcome Measures

Primary Outcomes (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

  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

  4 months

Study Arms (1)

Methotrexate / Etoposide Infusion

EXPERIMENTAL

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; Drug: Etoposide; Procedure: Ommaya Reservoir

Interventions

Methotrexate DRUG

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.

Also known as: Trexall, Rasuvo

Methotrexate / Etoposide Infusion

Etoposide DRUG

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.

Also known as: VePesid, Toposar, Etopophos

Methotrexate / Etoposide Infusion

Ommaya Reservoir PROCEDURE

Surgical catheter placement into the fourth ventricle of the brain

Methotrexate / Etoposide Infusion

Eligibility Criteria

• Age: 1 Year - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• The University of Texas Health Science Center, Houston: lead

Study Sites (1)

UTHealth & Children's Memorial Hermann Hospital

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Brain Neoplasms; Medulloblastoma; Ependymoma; Rhabdoid Tumor

Interventions

Methotrexate; Etoposide; etoposide phosphate

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neuroectodermal Tumors, Primitive; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neoplasms, Complex and Mixed

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates

Study Officials

• David Sandberg, MD

  UTHealth

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Pediatric Neurosurgery, Associate Professor Pediatric Surgery and Neurosurgery

Study Record Dates

• First Submitted: September 7, 2016
• First Posted: September 19, 2016
• Study Start: October 12, 2017
• Primary Completion: March 4, 2022
• Study Completion: March 4, 2022
• Last Updated: March 25, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)