Brain Tumor, RecurrentPhase 1NCT02458339
Methotrexate Infusion Into Fourth Ventricle in Children With Recurrent Malignant Fourth Ventricular Brain Tumors
A Phase 1 study testing Ommaya Reservoir and Methotrexate in people with Brain Tumor, Recurrent and Malignant Neoplasm of Fourth Ventricle of Brain, run by The University of Texas Health Science Center, Houston at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 1 year to 21 years
- Conditions the study is for
- Brain Tumor, Recurrent, Malignant Neoplasm of Fourth Ventricle of Brain
- What is being tested?
- Ommaya Reservoir and Methotrexate
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Jun 2015to 1 Mar 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
UTHealth & Children's Memorial Hermann Hospital
Houston, Texas, 77030
About this study
Official title: Phase I Study of Methotrexate Infusion Into the Fourth Ventricle in Children With Recurrent Malignant Fourth Ventricular Brain Tumors
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.
Read the detailed description
If the participant is eligible to take part in this study, the participant 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. This catheter will be used 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 the participant is already under anesthesia just before the catheter is placed.
Study Drug Administration:
The participant will receive 3 cycles of intraventricular methotrexate into the fourth ventricle. Each cycle will be of 4 weeks duration. During the first 3 weeks (Day 1-7 weekly) methotrexate will be infused twice weekly on days 1 and 4 (+/-2 days). The 4th week will be a rest week.
Methotrexate will be infused through the ommaya reservoir catheter directly into the 4th ventricle of the brain starting at a minimum of 7 days after the catheter placement surgery. A MRI will be done to confirm adequate cerebrospinal fluid flow. The infusion should last about 3 minutes each time.
If the participant already has an ommaya catheter, methotrexate will begin after an MRI has confirmed adequate cerebrospinal fluid flow.
Study Visits:
Prior to Cycle 1:
- Medical history will be reviewed and any updates to health will be recorded
- A physical with vital signs and neurological exam will be done.
- Blood (about 1 teaspoon) will be drawn for routine test
- A MRI scan of the brain and spine will be done to check the status of the disease.
On the days of Methotrexate Infusion:
- A physical with vital signs and neurological exam will be done
- A 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.
Within 7 days of completing Cycle 3:
- A physical with vital signs and neurological exam will be done.
- A lumbar puncture will be done.
- A MRI scan of the brain and spine will be done to check the status of the disease.
Length of Study:
The participant will receive up to 3 cycles of the methotrexate, as long as the doctor thinks it is in their best interest. The participant will no longer be able to receive the study drug if the disease gets worse, if intolerable side effects occur, or if unable to follow study directions.
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 18 patients will be enrolled in this study. All will be enrolled at Children's Memorial Hermann Hospital.
- Being tested
- Ommaya Reservoir, Methotrexate
- Keywords
- Brain tumor, Malignant Fourth Ventricular Brain Tumors
- Medical subject headings
- Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ommaya ReservoirProcedure or surgery
Surgical catheter placement into the fourth ventricle of the brain
MethotrexateDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Procedure: Ommaya Reservoir; Drug: Methotrexate |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jun 2015 (estimated)
- Study start15 Jun 2015
- Primary completion1 Mar 2019
- Study completion1 Mar 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Brain Tumor, RecurrentStudies of the same condition, open and under way.
- More trials run by The University of Texas Health Science Center, HoustonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, David Ilan Sandberg, The University of Texas Health Science Center, Houston
- Investigators
- David I Sandberg, MD, Principal investigator, UTHealth Medical School
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02458339
- Sponsor's protocol ID
- HSC-MS-15-0035
- Status last verified
- Mar 2019
- First submitted
- 20 May 2015
- Last updated
- 6 Mar 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of Methotrexate Infusion Into the Fourth Ventricle in Children With Recurrent Malignant Fourth Ventricular Brain Tumors
- ClinicalTrials.gov ID
- NCT02458339
- Acronym / sponsor ID
- HSC-MS-15-0035
- Keywords
- Brain tumor, Malignant Fourth Ventricular Brain Tumors
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- The University of Texas Health Science Center, HoustonUniversity, hospital or other
- Study start
- 15 Jun 2015 (actual)
- Primary completion
- 1 Mar 2019 (actual)
- Study completion
- 1 Mar 2019 (actual)
- First posted
- 1 Jun 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
If the participant is eligible to take part in this study, the participant 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. This catheter will be used 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 the participant is already under anesthesia just before the catheter is placed.
Study Drug Administration:
The participant will receive 3 cycles of intraventricular methotrexate into the fourth ventricle. Each cycle will be of 4 weeks duration. During the first 3 weeks (Day 1-7 weekly) methotrexate will be infused twice weekly on days 1 and 4 (+/-2 days). The 4th week will be a rest week.
Methotrexate will be infused through the ommaya reservoir catheter directly into the 4th ventricle of the brain starting at a minimum of 7 days after the catheter placement surgery. A MRI will be done to confirm adequate cerebrospinal fluid flow. The infusion should last about 3 minutes each time.
If the participant already has an ommaya catheter, methotrexate will begin after an MRI has confirmed adequate cerebrospinal fluid flow.
Study Visits:
Prior to Cycle 1:
- Medical history will be reviewed and any updates to health will be recorded
- A physical with vital signs and neurological exam will be done.
- Blood (about 1 teaspoon) will be drawn for routine test
- A MRI scan of the brain and spine will be done to check the status of the disease.
On the days of Methotrexate Infusion:
- A physical with vital signs and neurological exam will be done
- A 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.
Within 7 days of completing Cycle 3:
- A physical with vital signs and neurological exam will be done.
- A lumbar puncture will be done.
- A MRI scan of the brain and spine will be done to check the status of the disease.
Length of Study:
The participant will receive up to 3 cycles of the methotrexate, as long as the doctor thinks it is in their best interest. The participant will no longer be able to receive the study drug if the disease gets worse, if intolerable side effects occur, or if unable to follow study directions.
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 18 patients will be enrolled in this study. All will be enrolled at Children's Memorial Hermann Hospital.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Experimental | Experimental | Procedure: Ommaya Reservoir, Drug: Methotrexate3 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. |
Who may qualify
- Ages
- 1 year to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ommaya ReservoirSurgical catheter placement into the fourth ventricle of the brain | Procedure or surgery | Experimental |
| Methotrexate4, 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. | Drug | Experimental |
Primary outcome
Maximum Tolerated Dose (MTD) of the direct administration of methotrexate into the fourth ventricle of the brain as determined by NCI's CTCAE
Time frame: 3 months
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).
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Mar 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David I Sandberg, MD principal investigator
UTHealth Medical School
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ommaya Reservoir and Methotrexate in people with Brain Tumor, Recurrent and Malignant Neoplasm of Fourth Ventricle of Brain, run by The University of Texas Health Science Center, Houston at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose (MTD) of the direct administration of methotrexate into the fourth ventricle of the brain as determined by NCI's CTCAE (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Mar 2019.