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

Study Description

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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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Study Design

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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

Arms and Interventions

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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

Outcome Measures

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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

Eligibility Criteria

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Ages Eligible for Study:	1 Year to 21 Years (Child, Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• Age 1 - 21 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

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Contacts

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

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

Principal Investigator:	David Sandberg, MD	UTHealth

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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
Last Update Posted:	August 22, 2017
Last Verified:	August 2017
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

Additional relevant MeSH terms:

Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; 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