Methotrexate Infusion Into the Fourth Ventricle in Children With Malignant Fourth Ventricular Brain Tumors: A Pilot Study

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01737671
First received: November 27, 2012
Last updated: April 7, 2015
Last verified: April 2015
  Purpose

The goal of this clinical research study is to learn if it is safe to receive methotrexate through the fourth ventricle of the brain in patients with brain tumors.

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.


Condition Intervention
Brain Tumor
Malignant Neoplasm of Fourth Ventricle of Brain
Procedure: Ommaya Reservoir
Drug: Methotrexate
Drug: Leucovorin

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Methotrexate Infusion Into the Fourth Ventricle in Children With Malignant Fourth Ventricular Brain Tumors: A Pilot Study

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Neurological Deficits After Administration of Methotrexate into the Fourth Ventricle of the Brain [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    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 infusions.


Estimated Enrollment: 12
Study Start Date: December 2012
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Methotrexate Infusion
3 consecutive cycles of intraventricular methotrexate infusions into implanted fourth ventricle catheter/Ommaya reservoir following surgical catheter placement into fourth ventricle, each cycle is 4 consecutive daily doses of intraventricular methotrexate with minimum 2 weeks between cycles. If any serum methotrexate level is > 0.3 micromolar, then Leucovorin therapy administered (5 mg/square meter per dose) every 6 hours by vein or mouth.
Procedure: Ommaya Reservoir
Surgical catheter placement into the fourth ventricle of the brain.
Drug: Methotrexate
2 mg into fourth ventricle of the brain via the Ommaya Reservoir for 4 days. Each patient will undergo three cycles with at least two weeks between each cycle.
Drug: Leucovorin
5 mg/square meter per dose administered every 6 hours by vein or mouth.
Other Names:
  • Citrovorum
  • Wellcovorin

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   up to 22 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. There will be a two-step process of eligibility assessment: Step 1: Eligibility for catheter placement and possible surgical removal of tumor. Step 2: Eligibility for methotrexate infusion.
  2. Step 1 Eligiblity (Pre-Operative Eligiblity) Includes: Diagnosis and Age - Patients with tumor originally located within the posterior fossa of the brain: *Patients ≤ age 21 years with recurrent medulloblastoma (PNET) involving the brain and/or spine *Patients ≤ age 21 years with recurrent ependymoma involving the brain and/or spine *Patients ≤ age 21 years with recurrent atypical teratoid/rhabdoid tumor (AT/RT) involving the brain and/or spine.
  3. Step 1 Elig.: Life Expectancy - Patients must have a life expectancy of at least 12 weeks as estimated by the treating oncologist and neurosurgeon to be considered for enrollment.
  4. Step 1 Elig: Central Nervous System Function - Patients may be enrolled in the study if they have an altered neurological status, such as somnolence, which is attributed to hydrocephalus and/or mass effect from the brain tumor by the treating physicians. However, after tumor resection and placement of the catheter into the fourth ventricle, the protocol will only be continued if the patient has adequate central nervous system function, defined as: patient is not severely somnolent or comatose and has adequate clinical performance status as defined in protocol section 3.2.2.1.
  5. Step 2 Elig. (MTX Infusion Elig.): Clinical Performance Status - Patients must have a Lansky score of 50 or greater if ≤ 16 years of age and a Karnofsky score of 50 or greater if they are > 16 years of age to be eligible for enrollment (See Protocol Section 14.1 for Lansky Play-Performance Scale information; See Protocol Section 14.2 for Karnofsky Performance Scale information).
  6. Step 2 Elig: Pregnancy - Female patients who are post-menarchal must have a negative pregnancy test to be eligible. Pregnant or lactating female patients are ineligible.
  7. Step 2 Elig: Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study. a. Myelosuppressive chemotherapy: Must not have received within 2 weeks of entry onto this study. b. Hematopoietic Growth Factors: At least 7 days since the completion of therapy with a growth factor. c. Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy with a biologic agent. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. These patients must be discussed with the study chair on a case by case basis.
  8. Step 2 Elig: Bone Marrow Function - patients must have adequate bone marrow function, defined as: a. Peripheral absolute neutrophil count (ANC) ≥ 1000/µL b. Platelet count ≥ 30,000/µL (transfusion independent) c. Hemoglobin ≥ 9.0 gm/dL (may receive RBC transfusions) d. Post-op CSF flow study shows re-establishment of CSF flow.
  9. All patients and/or their parents or legal guardians must sign a written informed consent.

Exclusion Criteria:

  1. Patients will be excluded from this study if currently enrolled in another experimental treatment protocol.
  2. Patients will be excluded from this study if they have any evidence of infection, in any site, at the time of considered enrollment.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01737671

Locations
United States, Texas
Children's Memorial Hermann Hospital
Houston, Texas, United States, 77030
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Study Chair: Soumen Khatua, MD M.D. Anderson Cancer Center
Principal Investigator: David Sandberg, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01737671     History of Changes
Other Study ID Numbers: 2012-0823, NCI-2013-00045
Study First Received: November 27, 2012
Last Updated: April 7, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Brain tumor
Malignant Fourth Ventricular Brain Tumors
Ependymoma involving brain
Ependymoma involving spine
Recurrent ependymoma involving brain and/or spine
Recurrent atypical teratoid/rhabdoid tumor involving brain
Recurrent atypical teratoid/rhabdoid tumor involving spine
AT/RT
Ommaya reservoir catheter
Methotrexate
Medulloblastoma
ATRT
Atypical teratoid rhabdoid tumor
Ependymoma
Pediatric brain tumor
Intraventricular chemotherapy

Additional relevant MeSH terms:
Brain Neoplasms
Neoplasms
Brain Diseases
Central Nervous System Diseases
Central Nervous System Neoplasms
Neoplasms by Site
Nervous System Diseases
Nervous System Neoplasms
Methotrexate
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antirheumatic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 27, 2015