Methotrexate Infusion Into the Fourth Ventricle in Children With Malignant Fourth Ventricular Brain Tumors: A Pilot Study
N/A
22 Years
Both
Brain Tumor, Malignant Neoplasm of Fourth Ventricle of Brain
Trial Information
Methotrexate Infusion Into the Fourth Ventricle in Children With Malignant Fourth Ventricular Brain Tumors: A Pilot Study
Catheter Placement Surgery:
If you are eligible to take part in this study, you will have surgery to place a catheter
into the ommaya reservoir. The ommaya reservoir is a catheter system that allows drugs to
be administered directly to parts of the brain. In this study, the catheter will be used to
collect about 1 teaspoon of cerebrospinal fluid (the fluid surrounding the brain and spinal
cord) to check the status of the disease and for the infusion of methotrexate directly into
the 4th ventricle of the brain, which is 1 of the 4 connected fluid-filled cavities in the
brain.
If the study doctor thinks it is necessary, based on the location of the tumor, the tumor
may also be removed while you are already under anesthesia just before the catheter is
placed.
Study Drug Administration:
Each cycle is 4 days long and will consist of 4 daily infusions of methotrexate. You will
receive up to 3 cycles, with at least a 2 week rest period between each cycle.
Methotrexate will be infused through the ommaya reservoir catheter directly into the 4th
ventricle of the brain starting 2-4 weeks after the catheter placement surgery. The
infusion should last about 3 minutes each time.
You may also be given leucovorin, a drug used to help prevent or treat the side effects of
methotrexate, by intravenous (IV) infusion through a catheter or port you have already had
placed in your arm. If the study doctor thinks it is needed, this infusion will be given
after each cycle to help with the possible side effects you may experience from
methotrexate. The infusion should last about 5 minutes each time.
Study Visits:
Within 72 hours after catheter placement surgery:
- Your medical history will be reviewed and any updates to your health will be recorded.
- You will have a physical exam, including measurement of your weight and vitals.
- You will have a neurological exam.
- Blood (about 1 teaspoon) will be drawn for routine tests.
- You will have an MRI scan of the brain and spine to check the status of the disease.
Ten (10) days after catheter placement surgery:
- Your medical history will be reviewed and any updates to your health will be recorded.
- You will have a physical exam, including measurement of your weight and vitals.
- You will have a neurological exam.
- Blood (about 1 teaspoon) will be drawn for routine tests.
- Cerebrospinal fluid (about 1 teaspoon) will be collected for routine tests.
- You will have a spinal tap (also called a lumbar puncture). A lumbar puncture is a
procedure where fluid surrounding the spinal cord is removed by inserting a needle into
the lower back. The affected area is numbed with local anesthetic during the procedure.
Within 1 week before the first dose of methotrexate, blood (about 1 teaspoon) will be drawn
for routine tests.
Daily during each methotrexate infusion:
- You will have a physical exam, including measurement of your weight and vitals.
- You will have a neurological exam.
- Blood (about 1 teaspoon) will be drawn for routine tests.
- You will have an Ommaya reservoir tap (a catheter is placed into the Ommaya reservoir
to give the methotrexate infusion).
- Cerebrospinal fluid (about 1 teaspoon) will be collected for routine tests.
After Cycle 1 is complete:
- Your medical history will be reviewed and any updates to your health will be recorded.
- You will have a physical exam, including measurement of your weight and vitals.
- You will have a neurological exam.
- Blood (about 1 teaspoon) will be drawn for routine tests.
- Cerebrospinal fluid (about 1 teaspoon) will be collected for routine tests.
- You will have an MRI scan of the brain to check the status of the disease. If the
study doctor thinks it is needed, you will also have an MRI of the spine.
- If the study doctor thinks it is needed, you will have a lumbar puncture.
After Cycle 2 is complete:
- Your medical history will be reviewed and any updates to your health will be recorded.
- You will have a physical exam, including measurement of your weight and vitals.
- You will have a neurological exam.
- Blood (about 1 teaspoon) will be drawn for routine tests.
- Cerebrospinal fluid (about 1 teaspoon) will be collected for routine tests.
- If the study doctor think it is necessary, you will have a lumbar puncture.
After Cycle 3 is complete:
- Your medical history will be reviewed and any updates to your health will be recorded.
- You will have a physical exam, including measurement of your weight and vitals.
- You will have a neurological exam.
- Cerebrospinal fluid (about 1 teaspoon) will be collected for routine tests.
- You will have a lumbar puncture.
- If the study doctor thinks it is needed, you will have an MRI scan of the brain and
spine to check the status of the disease.
Length of Study:
You will receive up to 3 cycles of the methotrexate, as long as the doctor thinks it is your
best interest. You will no longer be able to receive the study drug if the disease gets
worse, if intolerable side effects occur, or if you are unable to follow study directions.
Your participation on the study will be over after you complete the follow-up visits.
Follow-Up Visits:
At 3, 6, 9, and 12 months after the last dose of study drug:
- Your medical history will be reviewed and any updates to your health will be recorded.
- You will have a physical exam, including measurement of your weight and vitals.
- You will have a neurological exam.
- You will have an MRI scan of the brain and spine to check the status of the disease.
The MRI of the spine may not be performed at months 3 and/or 6, if the study doctor
thinks it is in your best interest.
This is an investigational study. Methotrexate is FDA approved and commercially available
for infusion directly into brain tumors. The infusion of methotrexate into the 4th
ventricle of the brain is investigational.
Up to 10 patients will be enrolled in this study. All will be enrolled at MD Anderson.
Inclusion Criteria:
1. Patients under the age of 22 years with recurrent medulloblastoma (PNET) involving
the brain and/or spine, or recurrent ependymoma involving the brain and/or spine, or
recurrent atypical teratoid/rhabdoid tumor (AT/RT) involving the brain and/or spine.
2. Patients must have a life expectancy of at least 12 weeks as estimated by the
treating oncologist and/or neurosurgeon to be considered for enrollment.
3. Patients must have a Lansky score of 20 or greater Karnofsky score of 20 or greater > 16 years of age to be eligible for enrollment.
4. Female patients who are post-menarchal must have a negative pregnancy test to be
eligible.
5. 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
6. Prior to receiving intraventricular methotrexate, patients must have adequate bone
marrow function, defined as: Peripheral absolute neutrophil count (ANC) >/= 1000/µL,
Platelet count = 30,000/µL (transfusion independent), Hemoglobin = 9.0 gm/dL (may
receive RBC transfusions)
7. 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 or if receiving any other chemotherapy (either
systemic or intrathecal).
2. Pregnant or lactating female patients are ineligible
3. Patients will be excluded from this study if they have received another
investigational or chemotherapy agent within 14 days prior to study entry.
4. Patients will be excluded from this study if they have any evidence of infection in
any site at the time of considered enrollment.
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Neurological Deficits After Administration of Methotrexate into the Fourth Ventricle of the Brain
Outcome Description:
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.
Outcome Time Frame:
3 months
Safety Issue:
No
Principal Investigator
Soumen Khatua, MD
Investigator Role:
Study Chair
Investigator Affiliation:
UT MD Anderson Cancer Center
Authority:
United States: Food and Drug Administration
Study ID:
2012-0823
NCT ID:
NCT01737671
Start Date:
December 2012
Completion Date:
Related Keywords:
- Brain Tumor
- Malignant Neoplasm of Fourth Ventricle of Brain
- 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
- Brain Neoplasms
- Neoplasms
Name | Location |
|---|---|
| UT MD Anderson Cancer Center | Houston, Texas 77030 |
| Children's Memorial Hermann Hospital | Houston, Texas 77030 |
