Recurrent EpendymomaPhase 1NCT06466798
Fourth Ventricular Administration of Immune Checkpoint Inhibitor (Nivolumab) and Methotrexate or 5-Azacytidine for Recurrent Medulloblastoma, Ependymoma, and Other CNS Malignancies
A Phase 1 study testing Nivolumab, Methotrexate and 5-Azacytidine in people with Recurrent Ependymoma and Recurrent Medulloblastoma, run by Jeffrey Treiber.
Trial summary
The goal of this clinical trial is to assess the safety, toxicity, and antitumor activity of fourth ventricular infusions of nivolumab plus 5-azacytidine for recurrent ependymoma and nivolumab plus methotrexate for recurrent medulloblastoma and other CNS malignancies. Read more about this study
- Who is it for?
- Ages 1 year to 80 years
- Conditions the study is for
- Recurrent Ependymoma, Recurrent Medulloblastoma, CNS Malignancies
- What is being tested?
- Nivolumab, Methotrexate and 5-Azacytidine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 15 Jul 2024to 1 Jul 2027
- 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 80 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Age 1 - 80 years at time of recurrence or progression
- Minimum body weight of 10 kilograms
- Diagnosis: Patients with histologically verified medulloblastoma, ependymoma, with recurrence or progression anywhere in the brain and/or spine. Patients are also eligible if they have refractory disease, which will be defined as residual tumor which has not been completely cleared despite prior treatments. To be eligible, patients' disease must have originated or recurred in the posterior fossa of the brain. Patients with central nervous system (CNS) malignancies besides medulloblastoma and ependymoma are also eligible if they have recurrent or refractory disease in the posterior fossa
- Patient must have either measurable or evaluable tumor as assessed by magnetic resonance imaging (MRI) of the brain and total spine. If the patient does not have measurable or evaluable tumor after surgery for resection and catheter placement, infusions will be held until there is measurable or evaluable tumor on subsequent MRI scans. Patients with no measurable or evaluable disease after surgical resection cannot receive other systemic or intraventricular therapies and remain on study. If patients or their guardians choose to pursue additional systemic or intraventricular therapies during this time, the patients will be removed from the study. If patients do not receive additional systemic or intraventricular therapies and the is measurable or evaluable disease on subsequent imaging studies, then infusions may proceed according to the study protocol.
- An implanted catheter in the fourth ventricle or posterior fossa tumor cavity attached to a ventricular access device or agreement to have one placed.
- Patients must have received their last dose of known myelosuppressive anticancer therapy at least 21 days prior to enrollment or at least 42 days if nitrosourea
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- For patients receiving biologic or investigational agents (anti-neoplastic), the last dose must have been received at least 7 days prior to study enrollment. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which such events are known to occur
- For patients receiving monoclonal antibody treatment and agents with prolonged half-lives, the last dose of the agent must have been received at least 28 days prior to study enrollment
- For patients receiving Immune Effector Cell (IEC) Therapy (e.g., Chimeric antigen receptor (CAR) T-cells), viral therapy, or cellular therapy, patients must have received therapy ≥ 3 months prior to study enrollment. Patients who have received allogeneic stem cell transplants must wait at least 6 months prior to enrollment with no evidence of active graft versus host disease. Patients who have received autologous stem cell transplants must wait at least 3 months since transplant to enroll.
- Patients must have received their last fraction of standard upfront radiation ≥ 3 months prior to enrollment and ≥ 28 days for palliative radiation.
- Life expectancy of at least 12 weeks in the opinion of the principal investigator
- Lansky score of 50 or greater if ≤16 years of age or Karnofsky score of 50 or greater if > 16 years of age
- Patients must have recovered from the acute toxic effects of all prior anticancer chemotherapy
- Patients must have adequate organ and marrow function as defined below:
- Absolute neutrophil count > 1.0 x 10^9 cells/L
- Platelets > 50 x 10^9 cells/L (unsupported, defined as no platelet transfusion within 7 days)
- Hemoglobin ≥ 8 g/dL (may receive transfusions)
- Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)
- prothrombin time test with an international normalized ratio (PT/INR), partial thromboplastin time (PTT) ≤ 1.5 x ULN
- Alanine aminotransferase (ALT) [serum glutamic-pyruvic transaminase (SGPT)] and aspartate aminotransferase (AST) [serum glutamic-oxaloacetic transaminase (SGOT)] < 3 x institutional upper limit of normal (ULN)
- Albumin ≥ 3 g/dL
- Normal creatinine level for age according to hospital or outside lab standards. If creatinine is outside normal range, then Chronic kidney disease (CKD)-epi calculation will be performed for patients age >25. Patients age > 25 with estimated glomerular filtration rate (eGFR) > 60 ml/min/1.73m2 will be eligible and patients who do not meet this standard require nephrologist consultation to determine safety of enrollment. For patients ages 1 to 25 with creatinine outside normal range, Chronic kidney disease (CKD)--U25 calculation will be performed. Patients ages 1 to 25 with eGFR > 40 ml/min/1.73m2 will be eligible and patients who do not meet this standard require nephrologist consultation to determine safety of enrollment.
- Patient or patient's legal representative, parent(s), or guardian able to provide written informed consent.
- Patients of childbearing age and their parents will be informed that pregnancy is an exclusion criterion for the study. Male patients will be informed to use condoms if sexually active. Female patients will be advised to use contraceptives to prevent pregnancy if sexually active including male or female condoms, oral contraceptives, contraceptive injections, or other forms of contraception advised by primary care physician or obstetrician/gynecologist
Who cannot join
- Enrolled in another treatment protocol
- Patient is currently receiving corticosteroids that cannot be weaned off at least one week prior to first Nivolumab infusion
- Evidence of untreated infection
- Pregnant or lactating women
- Patient that has had allogenic stem cell transplant
About this study
The goal of this clinical trial is to assess the safety, toxicity, and antitumor activity of fourth ventricular infusions of nivolumab plus 5-azacytidine for recurrent ependymoma and nivolumab plus methotrexate for recurrent medulloblastoma and other CNS malignancies.
Additionally, the study will explore immunologic responses to nivolumab.
The hypothesis is that local administration of nivolumab, an immune checkpoint inhibitor, is safe and will lead to even more robust treatment responses when administered following 5-azacytidine in patients with recurrent ependymoma or methotrexate in patients with medulloblastoma or other CNS tumors.
- Being tested
- Nivolumab, Methotrexate, 5-Azacytidine
- Medical subject headings
- Ependymoma, Medulloblastoma, Central Nervous System Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NivolumabDrug
Nivolumab infusions will be given intraventricularly once every other week for 12 weeks. Dosing will be based upon patient body weight.
MethotrexateDrug
2 mg methotrexate infusions will be given intraventricularly daily for 4 consecutive days per week every other week for 12 weeks.
5-AzacytidineDrug
10 mg 5-Azacytidine infusions will be given intraventricularly once weekly for twelve consecutive weeks.
| Study group | Role | What they receive |
|---|---|---|
| Nivolumab plus Methotrexate | Experimental | Enrolled patients with medulloblastoma and other CNS malignancies will receive:
1. Intraventricular Methotrexate infusions 2 mg daily for 4 consecutive days per week every other week on weeks 1, 3, 5, 7, 9, and 11.
2. Intraventricular Nivolumab infusions. Nivolumab will be administered once every other week on weeks 2, 4, 6, 8, 10, and 12. Dosing will be based upon patient body weight. Receives: Drug: Nivolumab; Drug: Methotrexate |
| Nivolumab plus 5-Azacytidine | Experimental | Enrolled patients with ependymoma will receive:
1. Intraventricular 5-Azacytidine infusions 10 mg once weekly for twelve consecutive weeks.
2. Intraventricular Nivolumab infusions once every other week on weeks 1, 3, 5, 7, 9, and 11. Dosing will be based upon patient body weight. Receives: Drug: Nivolumab; Drug: 5-Azacytidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety as assessed by the number of participants with a new neurological toxicity that is graded as Grade 3 or higher and that is probably or definitely related to infusions [that is, classified as dose-limiting toxicity (DLT)]
Adverse events will be graded according to the NCI common terminology criteria version 5.0. Adverse events not included in the Common Terminology Criteria for Adverse Events (CTCAE) chart will be graded as follows:
- Grade 1: Mild: discomfort present with no disruption of daily activity, no treatment required beyond prophylaxis
- Grade 2: Moderate: discomfort present with some disruption of daily activity, require treatment.
- Grade 3: Severe: discomfort that interrupts normal daily activity, not responding to first line treatment.
- Grade 4: Life Threatening: discomfort that represents immediate risk of death.
Measured: from start of treatment to end of treatment (about 12 weeks)
Secondary outcomes (1)
Number of participants who responded to therapy as determined by MRI imaging
Measured: baseline, within 7 days of completing final infusion (about 12 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jun 2024
- Study start15 Jul 2024
- Primary completion1 Jul 2027 (estimated)
- Study completion1 Jul 2027 (estimated)
Why it stopped: Inability to find participants meeting eligibility critieria
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Recurrent EpendymomaStudies of the same condition, open and under way.
- 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jeffrey Treiber
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Jeffrey Treiber, The University of Texas Health Science Center, Houston
- Investigators
- Jeffrey M. Treiber, MD, Principal investigator, The University of Texas Health Science Center, Houston
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06466798
- Sponsor's protocol ID
- HSC-MS-24-0240
- Status last verified
- Jan 2026
- First submitted
- 13 Jun 2024
- Last updated
- 8 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Fourth Ventricular Administration of Immune Checkpoint Inhibitor (Nivolumab) and Methotrexate or 5-Azacytidine for Recurrent Medulloblastoma, Ependymoma, and Other CNS Malignancies
- ClinicalTrials.gov ID
- NCT06466798
- Acronym / sponsor ID
- HSC-MS-24-0240
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Inability to find participants meeting eligibility critieria
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Jeffrey TreiberUniversity, hospital or other
- Study start
- 15 Jul 2024 (actual)
- Primary completion
- 1 Jul 2027 (estimated)
- Study completion
- 1 Jul 2027 (estimated)
- First posted
- 20 Jun 2024 (actual)
- 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 trial is to assess the safety, toxicity, and antitumor activity of fourth ventricular infusions of nivolumab plus 5-azacytidine for recurrent ependymoma and nivolumab plus methotrexate for recurrent medulloblastoma and other CNS malignancies.
Additionally, the study will explore immunologic responses to nivolumab.
The hypothesis is that local administration of nivolumab, an immune checkpoint inhibitor, is safe and will lead to even more robust treatment responses when administered following 5-azacytidine in patients with recurrent ependymoma or methotrexate in patients with medulloblastoma or other CNS tumors.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Nivolumab plus Methotrexate | Experimental | Drug: Nivolumab, Drug: MethotrexateEnrolled patients with medulloblastoma and other CNS malignancies will receive: 1. Intraventricular Methotrexate infusions 2 mg daily for 4 consecutive days per week every other week on weeks 1, 3, 5, 7, 9, and 11. 2. Intraventricular Nivolumab infusions. Nivolumab will be administered once every other week on weeks 2, 4, 6, 8, 10, and 12. Dosing will be based upon patient body weight. |
| Nivolumab plus 5-Azacytidine | Experimental | Drug: Nivolumab, Drug: 5-AzacytidineEnrolled patients with ependymoma will receive: 1. Intraventricular 5-Azacytidine infusions 10 mg once weekly for twelve consecutive weeks. 2. Intraventricular Nivolumab infusions once every other week on weeks 1, 3, 5, 7, 9, and 11. Dosing will be based upon patient body weight. |
Who may qualify
- Ages
- 1 year to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (24 listed)
- Age 1 - 80 years at time of recurrence or progression
- Minimum body weight of 10 kilograms
- Diagnosis: Patients with histologically verified medulloblastoma, ependymoma, with recurrence or progression anywhere in the brain and/or spine. Patients are also eligible if they have refractory disease, which will be defined as residual tumor which has not been completely cleared despite prior treatments. To be eligible, patients' disease must have originated or recurred in the posterior fossa of the brain. Patients with central nervous system (CNS) malignancies besides medulloblastoma and ependymoma are also eligible if they have recurrent or refractory disease in the posterior fossa
- Patient must have either measurable or evaluable tumor as assessed by magnetic resonance imaging (MRI) of the brain and total spine. If the patient does not have measurable or evaluable tumor after surgery for resection and catheter placement, infusions will be held until there is measurable or evaluable tumor on subsequent MRI scans. Patients with no measurable or evaluable disease after surgical resection cannot receive other systemic or intraventricular therapies and remain on study. If patients or their guardians choose to pursue additional systemic or intraventricular therapies during this time, the patients will be removed from the study. If patients do not receive additional systemic or intraventricular therapies and the is measurable or evaluable disease on subsequent imaging studies, then infusions may proceed according to the study protocol.
- An implanted catheter in the fourth ventricle or posterior fossa tumor cavity attached to a ventricular access device or agreement to have one placed.
Key exclusion criteria (5 listed)
- Enrolled in another treatment protocol
- Patient is currently receiving corticosteroids that cannot be weaned off at least one week prior to first Nivolumab infusion
- Evidence of untreated infection
- Pregnant or lactating women
- Patient that has had allogenic stem cell transplant
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 |
|---|---|---|
| NivolumabNivolumab infusions will be given intraventricularly once every other week for 12 weeks. Dosing will be based upon patient body weight. | Drug | Nivolumab plus 5-Azacytidine, Nivolumab plus Methotrexate |
| Methotrexate2 mg methotrexate infusions will be given intraventricularly daily for 4 consecutive days per week every other week for 12 weeks. | Drug | Nivolumab plus Methotrexate |
| 5-Azacytidine10 mg 5-Azacytidine infusions will be given intraventricularly once weekly for twelve consecutive weeks. | Drug | Nivolumab plus 5-Azacytidine |
Primary outcome
Safety as assessed by the number of participants with a new neurological toxicity that is graded as Grade 3 or higher and that is probably or definitely related to infusions [that is, classified as dose-limiting toxicity (DLT)]
Time frame: from start of treatment to end of treatment (about 12 weeks)
Adverse events will be graded according to the NCI common terminology criteria version 5.0. Adverse events not included in the Common Terminology Criteria for Adverse Events (CTCAE) chart will be graded as follows: * Grade 1: Mild: discomfort present with no disruption of daily activity, no treatment required beyond prophylaxis * Grade 2: Moderate: discomfort present with some disruption of daily activity, require treatment. * Grade 3: Severe: discomfort that interrupts normal daily activity, not responding to first line treatment. * Grade 4: Life Threatening: discomfort that represents immediate risk of death.
1 secondary outcome
Number of participants who responded to therapy as determined by MRI imaging
Time frame: baseline, within 7 days of completing final infusion (about 12 weeks)
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jan 2026.
- 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.
Jeffrey M. Treiber, MD principal investigator
The University of Texas Health Science Center, Houston
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Nivolumab, Methotrexate and 5-Azacytidine in people with Recurrent Ependymoma and Recurrent Medulloblastoma, run by Jeffrey Treiber.
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 24 inclusion and 5 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: withdrawn, as of the sponsor's last update on 8 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
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 was withdrawn before enrolling participants, so there are no results.
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?
Safety as assessed by the number of participants with a new neurological toxicity that is graded as Grade 3 or higher and that is probably or definitely related to infusions [that is, classified as dose-limiting toxicity (DLT)] (time frame: from start of treatment to end of treatment (about 12 weeks)). 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 8 Jan 2026.