Methotrexate Infusion Into Fourth Ventricle in Children With Recurrent Malignant Fourth Ventricular Brain Tumors

NCT02458339 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: HSC-MS-15-0035
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to establish the maximum tolerated dose (MTD) of direct administration of methotrexate into the fourth ventricle of the brain in patients with recurrent malignant brain tumors including medulloblastoma, primitive neuroectodermal tumors (PNET), atypical teratoid/rhabdoid tumors (AT/RT), and ependymoma. Methotrexate is designed to block cancer cells from dividing, which may slow or stop their growth and spread throughout the body. This may cause the cancer cells to die.

Conditions

Brain Tumor, Recurrent; Malignant Neoplasm of Fourth Ventricle of Brain

Keywords

Brain tumor; Malignant Fourth Ventricular Brain Tumors

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) of the direct administration of methotrexate into the fourth ventricle of the brain as determined by NCI's CTCAE

  Maximum Tolerated Dose (MTD) is determined using the criteria established by the National Cancer Institute's (NCI's) Common Terminology Criteria for Adverse Events V4.0 (CTCAE).

  3 months

Study Arms (1)

Experimental

EXPERIMENTAL

3 consecutive cycles of intraventricular methotrexate infusions into implanted fourth ventricle catheter/Ommaya reservoir following surgical catheter placement into fourth ventricle, each cycle will be of 4 weeks duration. During the first 3 weeks, methotrexate will be infused twice weekly on days 1 and 4 (+/- 2 days). The 4th week is a rest week.

Procedure: Ommaya Reservoir; Drug: Methotrexate

Interventions

Ommaya Reservoir PROCEDURE

Surgical catheter placement into the fourth ventricle of the brain

Experimental

Methotrexate DRUG

4, 6, or 8 mg into fourth ventricle of the brain via the Ommaya Reservoir for 2 days a week for 3 weeks with week 4 is a rest week. Each patient will undergo three cycles.

Experimental

Eligibility Criteria

• Age: 1 Year - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Diagnosis: Patients with histologically verified medulloblastoma, primitive neuroectodermal tumor (PNET), atypical teratoid/rhabdoid tumor (AT/RT), ependymoma, or choroid plexus carcinoma with recurrence or progression involving the brain and /or spine. Patients with these tumors who did not present at diagnosis in the posterior fossa but have relapsed in the posterior fossa will be eligible. Patients who initially presented with disease in the posterior fossa but have now relapsed outside the posterior fossa will also be eligible.
• 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 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 methotrexate 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 such as weakness, gait instability, cranial nerve deficits, or any other problems caused by the patient's disease or previous treatments 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 RBC 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 with in 7 days prior to methotrexate infusion into the fourth ventricle
• 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

Interventions

Methotrexate

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• David I Sandberg, MD

  UTHealth Medical School

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: 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, Departments of Pediatric Surgery and Neurosurgery UTHealth Medical School

Study Record Dates

• First Submitted: May 20, 2015
• First Posted: June 1, 2015
• Study Start: June 15, 2015
• Primary Completion: March 1, 2019
• Study Completion: March 1, 2019
• Last Updated: March 6, 2019

Record last verified: 2019-03

Locations

US (1)