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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01737671
Recruitment Status : Completed
First Posted : November 29, 2012
Last Update Posted : January 19, 2018
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

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 or disease Intervention/treatment Phase
Brain Tumor Malignant Neoplasm of Fourth Ventricle of Brain Procedure: Ommaya Reservoir Drug: Methotrexate Drug: Leucovorin Early Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 7 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Methotrexate Infusion Into the Fourth Ventricle in Children With Malignant Fourth Ventricular Brain Tumors: A Pilot Study
Actual Study Start Date : December 27, 2012
Actual Primary Completion Date : January 11, 2018
Actual Study Completion Date : January 11, 2018

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. Neurological Deficits After Administration of Methotrexate into the Fourth Ventricle of the Brain [ Time Frame: 3 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 infusions.

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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Ages Eligible for Study:   up to 22 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 Eligibility (Pre-Operative Eligibility) 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
  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.

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 identifier (NCT number): NCT01737671

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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
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Study Chair: Soumen Khatua, MD M.D. Anderson Cancer Center
Principal Investigator: David Sandberg, MD M.D. Anderson Cancer Center
Additional Information:
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Responsible Party: M.D. Anderson Cancer Center Identifier: NCT01737671    
Other Study ID Numbers: 2012-0823
NCI-2013-00045 ( Registry Identifier: NCI CTRP )
First Posted: November 29, 2012    Key Record Dates
Last Update Posted: January 19, 2018
Last Verified: January 2018

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
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
Ommaya reservoir catheter
Atypical teratoid rhabdoid tumor
Pediatric brain tumor
Intraventricular chemotherapy
Additional relevant MeSH terms:
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Brain Neoplasms
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors
Protective Agents
Vitamin B Complex