Brain Tumor RecurrentEarly Phase 15-AZANCT02940483
Infusion of 5-Azacytidine (5-AZA) Into the Fourth Ventricle in Children With Recurrent Posterior Fossa Ependymoma
A Early Phase 1 study testing 5-Azacytidine in people with Brain Tumor Recurrent, 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 safety of direct administration of 5-Azacytidine into the fourth ventricle of the brain or resection cavity in patients with recurrent posterior fossa ependymoma. Read more about this study
- Who is it for?
- Ages 1 year to 21 years
- Conditions the study is for
- Brain Tumor Recurrent
- What is being tested?
- 5-Azacytidine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Feb 2017to 28 Nov 2018
- Phase
- Early 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 ependymoma, with recurrence or progression involving anywhere in the brain and/or spine. To be eligible, patients' disease must have originated in the posterior fossa of the brain.
- 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 or posterior fossa tumor cavity attached to a ventricular access device 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 5-Azacytidine 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.
Show all 10Show fewer
- Existing neurological deficits 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 within 7 days prior to 5-Azacytidine infusion into the fourth ventricle.
- Evidence of untreated infection
- Pregnant of 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: Infusion of 5-Azacytidine (5-AZA) Into the Fourth Ventricle or Resection Cavity in Children With Recurrent Posterior Fossa Ependymoma: A Pilot Study
The goal of this clinical research study is to establish the safety of direct administration of 5-Azacytidine into the fourth ventricle of the brain or resection cavity in patients with recurrent posterior fossa ependymoma.
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 used for the infusion of 5-Azacytidine directly into the 4th ventricle of the brain, which is 1 or 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 12 weekly (+/- one day) 10 mg infusions of 5-Azacytidine.
5-Azacytidine 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 5-Azacytidine infusion will last 2-3 minutes.
If the participant already has an Ommaya catheter, 5-Azacytidine will begin after an MRI has confirmed adequate cerebrospinal fluid flow.
Study Visits:
Prior to first infusion:
Medical history will be reviewed and any updates to health will be recorded. Physical and Neurological exam with vital signs will be done. Blood (about 1 teaspoon) will be drawn for routine test. A lumbar puncture will be done. A MRI scan of the brain and spine will be done to check the status of the disease.
On the days of the 5-Azacytidine Infusion:
A neurological exam with vital signs will be done. A Ommaya reservoir tap (a catheter is placed into the Ommaya reservoir to give the 5-Azacytidine infusion.
Cerebrospinal fluid (about 1 teaspoon) will be collected for routine tests.
Within 7 days of completing the Final infusion:
A neurological exam with vital signs will be done. A lumbar puncture will be done. A MRI scan of the brain and spine will be done to check status of the disease.
Length of Study:
The participant will receive 12 infusions of 5-Azacytidine, 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 investigation study. 5-Azacytidine is FDA approved and commercially available to be given subcutaneous or into the bloodstream (intravenously) but has never been given in the 4th ventricle of the brain. The infusion of 5-Azacytidine into the 4th ventricle of the brain is investigational.
Up to 10 patients will be enrolled in this study. All will be enrolled at Children's Memorial Hermann Hospital
- Conditions
- Brain Tumor Recurrent
- Being tested
- 5-Azacytidine
- Keywords
- Ependymoma
- Medical subject headings
- Brain Neoplasms, Ependymoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
5-AzacytidineDrug
Also called Vidaza, Mylosar
5-Azacytidine 10 mg into the fourth ventricle of the brain via the Ommaya reservoir 1 day a week for 12 weeks.
| Study group | Role | What they receive |
|---|---|---|
| 5-Azacytidine Infusion | Experimental | 12 infusions (once a week) into implanted fourth ventricle catheter/Ommaya reservoir following surgical catheter placement into fourth ventricle. Receives: Drug: 5-Azacytidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients with grade 3 through grade 5 new neurological adverse events that are related to study drug, graded according to NCI CTCAE Version 4.0
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 5-Azacytidine infusions. Primary endpoint for basis of safety monitoring is acute toxicity occurring at any time within 30 days of receiving the intraventricular 5-Azacytidine infusion. Rate of acute toxicity monitored using Bayesian method of Thall and Sung. Method of Kaplan and Meier used to estimate unadjusted distributions o time to a neurological deficit and progression free survival time and summary statistic of all variable computed and tabulated.
Measured: 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Oct 2016 (estimated)
- Study start1 Feb 2017
- Primary completion28 Nov 2018
- Study completion28 Nov 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 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, M.D., Principal investigator, UTHealth
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02940483
- Sponsor's protocol ID
- HSC-MS-16-0739
- Acronym
- 5-AZA
- Status last verified
- Nov 2018
- First submitted
- 18 Oct 2016
- Last updated
- 30 Nov 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Lang F, Liu Y, Chou FJ, Yang C. Genotoxic therapy and resistance mechanism in gliomas. Pharmacol Ther. 2021 Dec;228:107922. doi: 10.1016/j.pharmthera.2021.107922. Epub 2021 Jun 23.
PubMed 34171339
Study at a glance
From the registry record, last updated by the sponsor on 30 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Infusion of 5-Azacytidine (5-AZA) Into the Fourth Ventricle or Resection Cavity in Children With Recurrent Posterior Fossa Ependymoma: A Pilot Study
- ClinicalTrials.gov ID
- NCT02940483
- Acronym / sponsor ID
- 5-AZA / HSC-MS-16-0739
- Conditions
- Brain Tumor Recurrent
- Keywords
- Ependymoma
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- The University of Texas Health Science Center, HoustonUniversity, hospital or other
- Study start
- 1 Feb 2017 (actual)
- Primary completion
- 28 Nov 2018 (actual)
- Study completion
- 28 Nov 2018 (actual)
- First posted
- 21 Oct 2016 (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 safety of direct administration of 5-Azacytidine into the fourth ventricle of the brain or resection cavity in patients with recurrent posterior fossa ependymoma.
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 used for the infusion of 5-Azacytidine directly into the 4th ventricle of the brain, which is 1 or 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 12 weekly (+/- one day) 10 mg infusions of 5-Azacytidine.
5-Azacytidine 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 5-Azacytidine infusion will last 2-3 minutes.
If the participant already has an Ommaya catheter, 5-Azacytidine will begin after an MRI has confirmed adequate cerebrospinal fluid flow.
Study Visits:
Prior to first infusion:
Medical history will be reviewed and any updates to health will be recorded. Physical and Neurological exam with vital signs will be done. Blood (about 1 teaspoon) will be drawn for routine test. A lumbar puncture will be done. A MRI scan of the brain and spine will be done to check the status of the disease.
On the days of the 5-Azacytidine Infusion:
A neurological exam with vital signs will be done. A Ommaya reservoir tap (a catheter is placed into the Ommaya reservoir to give the 5-Azacytidine infusion.
Cerebrospinal fluid (about 1 teaspoon) will be collected for routine tests.
Within 7 days of completing the Final infusion:
A neurological exam with vital signs will be done. A lumbar puncture will be done. A MRI scan of the brain and spine will be done to check status of the disease.
Length of Study:
The participant will receive 12 infusions of 5-Azacytidine, 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 investigation study. 5-Azacytidine is FDA approved and commercially available to be given subcutaneous or into the bloodstream (intravenously) but has never been given in the 4th ventricle of the brain. The infusion of 5-Azacytidine into the 4th ventricle of the brain is investigational.
Up to 10 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 |
|---|---|---|
| 5-Azacytidine Infusion | Experimental | Drug: 5-Azacytidine12 infusions (once a week) into implanted fourth ventricle catheter/Ommaya reservoir following surgical catheter placement into fourth ventricle. |
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 ependymoma, with recurrence or progression involving anywhere in the brain and/or spine. To be eligible, patients' disease must have originated in the posterior fossa of the brain.
- 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 or posterior fossa tumor cavity attached to a ventricular access device 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 5-Azacytidine 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 within 7 days prior to 5-Azacytidine infusion into the fourth ventricle.
- Evidence of untreated infection
- Pregnant of 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 |
|---|---|---|
| 5-AzacytidineAlso: Vidaza, Mylosar5-Azacytidine 10 mg into the fourth ventricle of the brain via the Ommaya reservoir 1 day a week for 12 weeks. | Drug | 5-Azacytidine Infusion |
Primary outcome
Number of patients with grade 3 through grade 5 new neurological adverse events that are related to study drug, graded according to NCI CTCAE Version 4.0
Time frame: 4 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 5-Azacytidine infusions. Primary endpoint for basis of safety monitoring is acute toxicity occurring at any time within 30 days of receiving the intraventricular 5-Azacytidine infusion. Rate of acute toxicity monitored using Bayesian method of Thall and Sung. Method of Kaplan and Meier used to estimate unadjusted distributions o time to a neurological deficit and progression free survival time and summary statistic of all variable computed and tabulated.
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 30 Nov 2018.
- Derived from this study: PubMed 34171339Lang F, Liu Y, Chou FJ, Yang C. Genotoxic therapy and resistance mechanism in gliomas. Pharmacol Ther. 2021 Dec;228:107922. doi: 10.1016/j.pharmthera.2021.107922. Epub 2021 Jun 23.
- Individual participant dataSharing planned: No
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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, M.D. principal investigator
UTHealth
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing 5-Azacytidine in people with Brain Tumor Recurrent, 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 30 Nov 2018. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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?
Number of patients with grade 3 through grade 5 new neurological adverse events that are related to study drug, graded according to NCI CTCAE Version 4.0 (time frame: 4 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02940483, which also lists 1 linked publication.
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 30 Nov 2018.