MedulloblastomaPhase 2NCT03173950

Immune Checkpoint Inhibitor Nivolumab in People With Recurrent Select Rare CNS Cancers

A Phase 2 study testing Nivolumab, EKG and MRI Brain and/or spine in people with Medulloblastoma and Ependymoma, run by National Cancer Institute (NCI) at 3 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Background: More than 130 primary tumors of the central nervous system (CNS) have been identified. Most affect less than 1,000 people in the United States each year. Because these tumors are so rare, there are few proven therapies. Read more about this study

Who is it for?: Ages 18 to 99 years
Conditions the study is for: Medulloblastoma, Ependymoma, Pineal Region Tumors
What is being tested?: Nivolumab, EKG and MRI Brain and/or spine
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 136 participants
Where: 3 sitesUnited States
Study dates: 13 Jul 2017to 23 Jun 2025
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 18 to 99 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Histopathologically proven diagnosis of Ependymoma, Medulloblastoma, Parenchymal Pineal Region Tumors (Pineoblastoma, Pineocytoma, Pineal Tumor of Intermediate Differentiation, Papillary Tumor of the Pineal Region), Choroid Plexus Tumors (Carcinoma, Papilloma, Atypical Papilloma), Histone Mutated Gliomas, Gliomatosis Cerebri, Atypical Teratoid/Rhabdoid Tumor (ATRT), Malignant/Atypical Meningioma*, Gliosarcoma or Primary CNS Sarcoma, Pleomorphic Xanthoastrocytoma (PXA) and Anaplastic Pleomorphic Xanthoastrocytoma (APXA), and tumors formerly known as Primitive Neuro-Ectodermal Tumors (Embryonal Tumor with Multilayered Rosettes, Medulloepithelioma, Central Nervous System (CNS) Neuroblastoma, CNS Ganglioneuroblastoma, CNS Embryonal Tumor NOS; and tumor entities emerging from methylation profiling of CNS-PNETs: CNS neuroblastoma with Forkhead box protein R2 (FOXR2) activation, CNS Ewing sarcoma family tumor with CIC alteration, CNS high-grade neuroepithelial tumor with meningioma 1 (MN1) alterations, and CNS high-grade neuroepithelial tumor with BCOR alteration) prior to registration.
Individuals with extra CNS metastases from meningioma will be eligible even if pathology review fails to demonstrate high grade features on available tumor samples.
The tumor tissue (e.g., block or 20 unstained slides) must be available to be sent for immunophenotyping by National Cancer Institute (NCI) Laboratory of Pathology.
Individuals must have progressive tumor growth after having received established standard of care and/or other experimental treatments for their newly diagnosed or recurrent disease. Individuals will be enrolled into 2 different cohorts (cohort 1 or heavily pretreated; cohort 2 or not heavily pretreated).
Age >= 18
Karnofsky performance status >= 70 within 14 days prior to Step 2 registration; Individuals with severe paraparesis/paraplegia who need minimal assistance for selfcare due to their motor deficit but are otherwise functionally independent will be considered eligible.

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Adequate hematologic function based on complete blood count (CBC)/differential within 14 days prior to Step 2 registration defined as follows:
Absolute neutrophil count >= 1,500 cells/mm^3;
Platelet count >= 100,000 cells/mm^3
Hemoglobin > 9.0 g/dl (may be transfused to achieve this level)
Adequate renal function within 14 days prior to Step 2 registration defined as follows:
Blood urea nitrogen (BUN) <= 30 mg/dl and
Serum creatinine <= 1.7 mg/dl
Note: If the serum creatinine is greater than 1.7 mg/dl, a 24-hour urine creatinine clearance will be obtained and if the result of this study is within normal limits, the patient would be eligible to enroll onto study. (Normal Creatinine Clearance Range: Male: 90 - 130 ml/min; Female: 80 - 125 ml/min)
Adequate hepatic function within 14 days prior to Step 2 registration defined as follows:
Total bilirubin (except patients with Gilbert's Syndrome, who are eligible for the study but exempt from the total bilirubin eligibility criterion) <= 2.0 mg/dl and
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <= 2.5x ULN
No active or chronic hepatitis infection. Hepatitis C virus (HCV) antibody (for Hepatitis C) and Hepatitis B Surface antigen and Hepatitis B core antibody must be negative. This has been routinely incorporated into immunotherapy trials with checkpoint inhibitors because of concerns that the risk of treatment-induced hepatic injury is increased in the setting of active viral hepatitis.
The individual must not be on a corticosteroid dose greater than physiologic replacement dosing defined as 30 mg of cortisone per day or its equivalent.
The individual must provide study-specific informed consent prior to study entry. No Durable Power of Attorney or Next of Kin can provide initial consent.
The effects of nivolumab on the developing human fetus are unknown. For this reason, women of childbearing potential (WOCBP) must use appropriate method(s) of contraception. WOCBP should use an adequate method to avoid pregnancy for 5 months (30 days plus the time required for nivolumab to undergo five half-lives) after the last dose of investigational drug.
NOTE: Based on the evidence cited in Nivolumab IB ver. 20, given that nivolumab is not a genotoxic agent, and that relevant systemic concentrations sufficient to produce a risk of fetal toxicity are not expected in individuals of childbearing potential (IOCBP) partners from exposure to an individual's seminal fluid, men that can father children will not be required to use contraceptive measures and/or a latex or other synthetic condom during sexual activity with an WOCBP partner.

Who cannot join

Individuals who are receiving any other investigational agents.
Prior use of an immunotherapy such as (but not limited to) a vaccine therapy, dendritic cell vaccine, other checkpoint inhibitors, or intracavitary or convectional enhanced delivery of chemotherapy.
Prior or concurrent malignancy unless its natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen.
Severe, active co-morbidity defined as follows:
Unstable angina within the last 6 months prior to Step 2 registration.
Transmural myocardial infarction within the last 6 months prior to Step 2 registration.

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Evidence of recent myocardial infarction or ischemia by the findings of S-T elevations of >= 2 mm using the analysis of an electrocardiogram (EKG) performed within 14 days prior to Step 2 registration.
New York Heart Association grade II or greater congestive heart failure requiring hospitalization within 12 months prior to Step 2 registration.
History of stroke, cerebral vascular accident (CVA) or transient ischemic attack within 6 months prior to Step 2 registration, with the exception of pericavitary ischemia due to tumor resection.
Serious and inadequately controlled cardiac arrhythmia.
Significant vascular disease (e.g., aortic aneurysm, history of aortic dissection) or clinically significant peripheral vascular disease.
Evidence of bleeding diathesis or coagulopathy.
Serious or non-healing wound, ulcer, or bone fracture or history of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess, major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Step 2 registration, with the exception of the craniotomy for tumor resection.
Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration.
Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration.
Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects.
Known acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol. The need to exclude participants with acquired immunodeficiency syndrome (AIDS) is based on the lack of information regarding the safety of nivolumab in patients with active HIV infection.
Active connective tissue disorders, such as lupus or scleroderma, which in the opinion of the treating physician may put the patient at high risk for immunologic toxicity.
Individuals with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids, should be excluded. These include but are not limited to individuals with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome or chronic inflammatory demyelinating polyneuropathyI (CIDP), myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and individuals with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should be excluded because of the risk of recurrence or exacerbation of disease.
Of note, individuals with vitiligo, endocrine deficiencies including thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible. Participants with rheumatoid arthritis and other arthropathies, Sjogren's syndrome and psoriasis controlled with topical medication and patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible. However, individuals with vitiligo, diabetes mellitus, and Hashimoto thyroiditis on appropriate replacement therapy may be enrolled.
Any other major medical illnesses or psychiatric impairments that in the investigator's opinion will prevent administration or completion of protocol therapy.
Allergies and Adverse Drug Reaction: History of allergy to study drug components.
Pregnancy or lactating women due to possible adverse effects on the developing fetus or infant due to study drug. Women of childbearing potential must have a negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin (HCG) within 24 hours prior to Step 2 registration.
History of severe hypersensitivity reaction to any monoclonal antibody.
Individuals unable to have magnetic resonance imaging (MRIs).

Trial locations and contacts

3 sites in 1 country.

United States3 sites

National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
Northwestern University
Chicago, Illinois, 60611
UT MD Anderson Cancer Center
Houston, Texas, 77030-4096

Other trials in United States

About this study

Official title: Phase II Trial of the Immune Checkpoint Inhibitor Nivolumab in Patients With Recurrent Select Rare CNS Cancers

Background:

More than 130 primary tumors of the central nervous system (CNS) have been identified. Most affect less than 1,000 people in the United States each year. Because these tumors are so rare, there are few proven therapies. This study will test whether the immunotherapy drug nivolumab is an effective treatment for people with rare CNS tumors.

Objectives:

To learn if stimulating the immune system using the drug nivolumab can shrink tumors in people with rare CNS (brain or spine) tumors or increase the time it takes for these tumors to grow or spread.

Eligibility:

Adults whose rare CNS tumor has returned.

Design:

Individuals will be screened:

Heart and blood tests
Physical and neurological exam
Hepatitis tests
Pregnancy test
Magnetic resonance imaging (MRI). They will lay in a machine that takes pictures.
Tumor tissue sample. This can be from a previous procedure.

At the start of the study, participants will have blood tests. They will answer questions about their symptoms and their quality of life.

Individuals will get nivolumab in a vein every 2 weeks for up to 64 weeks.

Individuals will have monthly blood tests. Every other month they will have an MRI and a neurologic function test. They will also answer questions about their quality of life.

Genetic tests will be done on individuals' tumor tissue. Individuals will be contacted if any clinically important results are found.

After treatment ends, individuals will be monitored for up to 5 years. They will have a series of MRIs and neurological function tests. They will be asked to report any symptoms they experience....

Read the detailed description

Background:

There are more than 130 identified primary tumors of the central nervous system (CNS). Most have an annual incidence of less than 1000 in the United States.
Given the rarity of each of the tumors listed above, there is a paucity of proven therapies. Most of these neoplasms are treated with maximum surgical resection followed by treatment with external beam radiotherapy. With few exceptions (medulloblastoma, adult ependymoma), there are no effective systemic regimens and even in chemotherapy sensitive disease, most patients with recurrence eventually have no remaining salvage treatments available.
In the setting of this unmet need, we propose to create a basket protocol that will evaluate the efficacy of the programmed cell death protein 1 (PD-1) inhibitor, nivolumab, in patients with refractory rare central nervous system neoplasms.
This study seeks to establish effective therapies at recurrence in patients with rare CNS tumors. We hypothesize that this therapy will improve progression free survival and/or objective responses.
It will be important to determine whether any determined survival benefit is associated with improvements in symptoms or does a worsening of symptoms offset the increase in survival. Precedence exists for measuring non-therapeutic endpoints in oncology research, and specifically in studies evaluating therapeutic benefit in patients with CNS tumors. There have been efforts in neuro-oncology to evaluate secondary endpoints using validated instruments as an additional indicator of benefit. The M.D. Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT) and Spine Tumor Module (MDASI-SP) allow for the self-reporting of symptom severity and interference with daily activities for patients with either brain or spinal cord tumors. The availability of validated instruments provides an opportunity to prospectively assess the impact of treatment, both positive and negative on patients.

Objective:

Determine the efficacy of nivolumab in a variety of recurrent, refractory primary central nervous system tumors as measured by disease control rate (confirmed complete response (CR)/partial response (PR) or durable stable disease (SD) for at least 6 months).

Eligibility:

Documented recurrent or progressive disease that corresponds to one of the tumors eligible for testing.
Age >= 18 years of age.
Karnofsky Performance >= 70%.
Tumor tissue available for central review to confirm morphologic diagnosis
Tumor tissue or slides must be available for central molecular and immune profiling.

Design:

This is an open label phase II clinical trial. Patients will be treated with the immune checkpoint inhibitor, nivolumab, at a standard dose of 240 mg intravenously every 2 weeks (+/- 3 days) for cycles 1 through 2, then doses of 480 mg every 4 weeks (+/- 3 days) for a total of 14 additional doses (cycles). A maximum of 18 treatments will be given (64 weeks).
A cycle will be defined as 4 weeks and patients will undergo efficacy assessments using MR imaging (and/or other imaging tests if applicable) every 2 cycles. Toxicity assessments will occur before the initiation of each cycle and patient outcomes measures (PROs) will be completed at the time of each imaging study (every 2 cycles) but prior to the patient being informed of the imaging results.
After completion of the planned treatment course or if treatment was stopped because of toxicity, patients will undergo imaging evaluations and PRO measurements every 8 weeks (or 2 months) for one year, then every 3 months for the next year, then every 4 months for the next year and then every 6 months while the patient remains on the protocol. Patients off treatment because of disease progression will not undergo future imaging or PRO assessments on this protocol.
Bayesian Optimal Phase 2 design (BOP2), will be used to conduct this phase II trial in patients with a variety of recurrent, refractory primary central nervous system tumors.
The study will be comprised of 2 disease cohorts: heavily pretreated (defined as having received 3 or more prior therapies) and non-heavily pretreated (defined as having received up to 2 prior therapies). Each cohort will be evaluated independently for efficacy.

Conditions: Medulloblastoma, Ependymoma, Pineal Region Tumors, Choroid Plexus Tumors, Atypical/Malignant Meningioma
Being tested: Nivolumab, EKG, MRI Brain and/or spine, Body CT Scan, MDASI-BT
Keywords: Immunotherapy, Anti-PD-1 Antibody, Brain Tumors, MDASI-BT, Spinal Cord Tumors
Medical subject headings: Medulloblastoma, Ependymoma, Pinealoma, Choroid Plexus Neoplasms, Meningioma, Brain Neoplasms, Spinal Cord Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

NivolumabDrug
Also called Opdivo
Individuals will receive nivolumab at standard dose of 240 mg intravenous (IV) every 2 weeks for cycles 1 through 2, then doses of 480 mg every 4 weeks for a total of 14 additional doses.
EKGDiagnostic test
Also called Electrocardiogram
Screening/baseline.
MRI Brain and/or spineDiagnostic test
Also called Magnetic resonance imaging brain and/or spine
Screening/baseline.
Body CT ScanDiagnostic test
Also called Body computed tomography
Screening/baseline.
MDASI-BTOther
Also called M.D. Anderson Symptom Inventory Brain Tumor (MDASI-BT)
Screening/baseline. During active treatment and post therapy follow up.
MDASI-SPOther
Also called M.D. Anderson Symptom Inventory Spine Tumor (MDASI-SP)
Screening/baseline. During active treatment and post therapy follow up.

Study groups in NCT03173950
Study group	Role	What they receive
Arm 1/Experimental Therapy - Nivolumab	Experimental	Individuals will receive nivolumab at standard dose of 240 mg intravenous (IV) every 2 weeks for cycles 1 through 2, then doses of 480 mg every 4 weeks for a total of 14 additional doses. Receives: Drug: Nivolumab; Diagnostic Test: EKG; Diagnostic Test: MRI Brain and/or spine; Diagnostic Test: Body CT Scan; Other: MDASI-BT; Other: MDASI-SP

What is being measured

The primary outcome is the main question the study is designed to answer.

Disease Control Rate (Complete Response (CR) + Partial Response (PR) or Durable Stable Disease (SD) for 6 Months Measured in a Variety of Recurrent Refractory Primary Central Nervous System Tumors Reported With Standard Deviation
Disease control rate (DCR) measured in a variety of recurrent refractory primary central nervous system tumors. DCR is defined as a confirmed CR/PR or durable stable disease (SD) for 6 months assessed by the Immunotherapy Response Assessment Neuro-Oncology (iRANO) criteria. Complete Response is complete disappearance of all enhancing measurable and non-measurable disease sustained for at least 4 weeks. Partial Response is ≥ 50% decrease compared to baseline in the sum of products of perpendicular diameters of all measurable enhancing lesions sustained for at least 4 weeks. Durable stable disease does not qualify for CR, PR or progression (>25% increase in the sum of the products of perpendicular diameters of enhancing lesions (over best response [smallest tumor size] or baseline if no decrease) on stable or increasing doses of corticosteroids. A single value was calculated (e.g. summed or averaged) by
Measured: From cycle one Day 1 of the treatment through the end of treatment, up to 64 weeks
Disease Control Rate (Complete Response (CR) + Partial Response (PR) or Durable Stable Disease (SD) for 6 Months Measured in a Variety of Recurrent Refractory Primary Central Nervous System Tumors Reported With a 95% Confidence Interval
Disease control rate (DCR) measured in a variety of recurrent refractory primary central nervous system tumors. DCR is defined as a confirmed CR/PR or durable stable disease (SD) for 6 months assessed by the Immunotherapy Response Assessment Neuro-Oncology (iRANO) criteria. Complete Response is complete disappearance of all enhancing measurable and non-measurable disease sustained for at least 4 weeks. Partial Response is ≥ 50% decrease compared to baseline in the sum of products of perpendicular diameters of all measurable enhancing lesions sustained for at least 4 weeks. Durable stable disease does not qualify for CR, PR or progression (i.e., >25% increase in the sum of the products of perpendicular diameters of enhancing lesions (over best response [smallest tumor size] or baseline if no decrease) on stable or increasing doses of corticosteroids. A single value was calculated (e.g. summed or averaged) by
Measured: From cycle one Day 1 of the treatment through the end of the treatment, up to 64 weeks
Progression Free Survival (PFS)
PFS is defined as the date of on-study to the date of disease progression or death, estimated with the Kaplan-Meier method and reported with a 95% confidence interval. Response was assessed by the Immunotherapy Response Assessment Neuro-Oncology (iRANO) criteria and estimated using the Kaplan-Meier method. Progressive Disease is >25% increase in sum of the products of perpendicular diameters of enhancing lesions (over best response [smallest tumor size] or baseline if no decrease) on stable or increasing doses of corticosteroids.
Measured: From cycle one Day 1 of the treatment through the end of the treatment, up to 64 weeks
Progression Free Survival at 6 Months With 95% Confidence Interval
PFS-6 is the rate of durable Stable Disease lasting at least 6 months defined from the day of study entry until imaging is confirmed to show disease progression reported with a 95% confidence interval based on the Brookmeyer-Crowley method. Response was assessed by the Immunotherapy Response Assessment Neuro-Oncology (iRANO) criteria and estimated using the Kaplan-Meier method. Progressive Disease is >25% increase in sum of the products of perpendicular diameters of enhancing lesions (over best response [smallest tumor size] or baseline if no decrease) on stable or increasing doses of corticosteroids.
Measured: 6 months after the initiation of treatment, up to 24 weeks

Secondary outcomes (7)

Overall Survival (OS)
OS is defined as the date of on-study to the date of death from any cause or last follow up, estimated with the Kaplan-Meier method and reported with a 95% confidence interval based on the Brookmeyer-Crowley method.
Measured: Time from the study entry and after initiation of nivolumab to participants death, up to 5 years
Mean Symptom Burden Severity and Interference Using the MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT) and MD Anderson Symptom Inventory-Spine Tumor (MDASI-SP) Module Reported With a 95% Confidence Interval, at Each Time Point
Symptom burden is composed of severity and interference as measured by the MD Anderson Symptom Inventory-Brain tumor (MDASI-BT) or MD Anderson Symptom Inventory-Spine Tumor. The MDASI-BT questionnaire contains 23 symptoms and 6 interference items. The MDASI-SP questionnaire contains 19 symptoms and 6 interference items. Symptom severity is the Mean of the 23 or 19 symptoms and ranges from 0 to 10. Symptom interference is the Mean of the 6 interference items and ranges from 0 to 10. Higher scores indicate worse symptoms or worse interference.
Measured: Baseline (Up to 14 days prior to treatment), and at time of imaging - cycle 2, 4, 6, 8, 10, and 12 (one cycle = 4 weeks)
Mean Symptom Burden Severity & Interference Using the MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT) & MD Anderson Symptom Inventory-Spine Tumor (MDASI-SP) Module Reported With Standard Deviation(SD) at Each Time Point
Symptom burden is composed of severity and interference as measured by the MD Anderson Symptom Inventory-Brain tumor (MDASI-BT) or MD Anderson Symptom Inventory-Spine Tumor. The MDASI-BT questionnaire contains 23 symptoms and 6 interference items. The MDASI-SP questionnaire contains 19 symptoms and 6 interference items. Symptom severity is the Mean of the 23 or 19 symptoms and ranges from 0 to 10. Symptom interference is the Mean of the 6 interference items and ranges from 0 to 10. Higher scores indicate worse symptoms or worse interference.
Measured: Baseline (up to 14 days prior to treatment), and at time of imaging - cycle 2, 4, 6, 8, 10, or 12 (one cycle = 4 weeks)
Mean Symptom Burden Severity and Interference Using the MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT) and MD Anderson Symptom Inventory-Spine Tumor (MDASI-SP) Between Responders and Non-responders Reported With 95% Confidence Interval
Symptom burden is composed of severity and interference as measured by the MD Anderson Symptom Inventory-Brain tumor (MDASI-BT) or MD Anderson Symptom Inventory-Spine Tumor. The MDASI-BT questionnaire contains 23 symptoms and 6 interference items. The MDASI-SP questionnaire contains 19 symptoms and 6 interference items. Symptom severity is the Mean of the 23 or 19 symptoms and ranges from 0 to 10. Higher scores indicate. Symptom interference is the Mean of the 6 interference items and ranges from 0 to 10. Higher scores indicate worse symptoms or worse interference. Response status was determined by whether disease progression occurred prior to or at cycle 6 or not. Participants who had disease progression prior to or at cycle 6 were non-responders and participants who did not have disease progression by cycle 6 were responders. Relevant MDASI-BT \& MDASI-SP data are those that correspond to the cycle where response status was determined. It is a unique cycle for each participant.
Measured: Two possible timepoints dependent on response status. Non-responders: determined by whether disease progression occurred prior to or at cycle 6 or not. Responders: cycle 6. One cycle= 4 weeks/participants who did not have disease progression by cycle 6.
Mean Symptom Burden Severity and Interference Using the MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT) and MD Anderson Symptom Inventory-Spine Tumor (MDASI-SP) Between Responders and Non-responders Reported With Standard Deviation
Symptom burden is composed of severity and interference as measured by the MD Anderson Symptom Inventory-Brain tumor (MDASI-BT) or MD Anderson Symptom Inventory-Spine Tumor. The MDASI-BT questionnaire contains 23 symptoms and 6 interference items. The MDASI-SP questionnaire contains 19 symptoms and 6 interference items. Symptom severity is the Mean of the 23 or 19 symptoms and ranges from 0 to 10. Higher scores indicate. Symptom interference is the Mean of the 6 interference items and ranges from 0 to 10. Higher scores indicate worse symptoms or worse interference. Response status was determined by whether disease progression occurred prior to or at cycle 6 or not. Participants who had disease progression prior to or at cycle 6 were non-responders and participants who did not have disease progression by cycle 6 were responders. Relevant MDASI-BT \& MDASI-SP data are those that correspond to the cycle where response status was determined. It is a unique cycle for each participant.
Measured: Two possible timepoints dependent on response status. Non-responders: determined by whether disease progression occurred prior to or at cycle 6 or not. Responders: cycle 6. One cycle= 4 weeks/participants who did not have disease progression by cycle 6.
Mean Change Scores in Symptom Burden Severity and Interference Using the MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT) and MD Anderson Symptom Inventory-Spine Tumor (MDASI-SP) Module Between Baseline and Even-numbered Cycle
Symptom burden is composed of severity and interference as measured by the MD Anderson Symptom Inventory-Brain tumor (MDASI-BT) or MD Anderson Symptom Inventory-Spine Tumor. The MDASI-BT questionnaire contains 23 symptoms and 6 interference items. The MDASI-SP questionnaire contains 19 symptoms and 6 interference items. Symptom severity is the Mean of the 23 or 19 symptoms and ranges from 0 to 10. Symptom interference is the Mean of the 6 interference items and ranges from 0 to 10. Higher scores indicate worse symptoms or worse interference. Mean change score is even-numbered cycle minus baseline. Hence, negative change scores indicate improvement.
Measured: Between Baseline (up to 14 days prior to treatment) and at time of imaging - cycle 2, 4, 6, 8, 10, and 12 (one cycle = 4 weeks)
Number of Grades 1, 2, 3, 4, and/or 5 Treatment Related Serious and/or Non-serious Adverse Events and Type
Here is the number of Grade 1, 2, 3, 4, and/or 5 serious and/or non-serious adverse events and type assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. Grade 1 is mild. Grade 2 is moderate. Grade 3 is severe. Grade 4 is life-threatening. Grade 5 is death related to adverse event.
Measured: Adverse Events were monitored/assessed from the first study intervention, Study Day 1 through 100 days after the study agent was last administered, up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

13 Jul 201723 Jun 2025

First posted2 Jun 2017
Study start13 Jul 2017
Primary completion23 Jun 2025
Study completion23 Jun 2025

Why it stopped: Support was withdrawn from study resulting in early termination of study. Investigator had to close study due to no drug supply.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (4)Papers the sponsor has linked to this study.
Other trials for MedulloblastomaStudies of the same condition, open and under way.
More trials run by National Cancer Institute (NCI)The 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 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 136 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03173950
Sponsor's protocol ID: 170102
Other IDs: 17-C-0102
Status last verified: Oct 2026
First submitted: 31 May 2017
Last updated: 27 Oct 2026
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request. In addition, all large-scale genomic sequencing data will be shared with subscribers to the database of Genotypes and Phenotypes (dbGaP).

Publications

Gilbert MR, Ruda R, Soffietti R. Ependymomas in adults. Curr Neurol Neurosci Rep. 2010 May;10(3):240-7. doi: 10.1007/s11910-010-0109-3.
PubMed 20425040
Okada H, Weller M, Huang R, Finocchiaro G, Gilbert MR, Wick W, Ellingson BM, Hashimoto N, Pollack IF, Brandes AA, Franceschi E, Herold-Mende C, Nayak L, Panigrahy A, Pope WB, Prins R, Sampson JH, Wen PY, Reardon DA. Immunotherapy response assessment in neuro-oncology: a report of the RANO working group. Lancet Oncol. 2015 Nov;16(15):e534-e542. doi: 10.1016/S1470-2045(15)00088-1.
PubMed 26545842
Daud AI, Loo K, Pauli ML, Sanchez-Rodriguez R, Sandoval PM, Taravati K, Tsai K, Nosrati A, Nardo L, Alvarado MD, Algazi AP, Pampaloni MH, Lobach IV, Hwang J, Pierce RH, Gratz IK, Krummel MF, Rosenblum MD. Tumor immune profiling predicts response to anti-PD-1 therapy in human melanoma. J Clin Invest. 2016 Sep 1;126(9):3447-52. doi: 10.1172/JCI87324. Epub 2016 Aug 15.
PubMed 27525433
Collins RRJ, Florke Gee RR, Tozandehjani S, Bayat T, Hoyos Sanchez MC, Gutierrez JSS, Breznik B, Lee AK, Peters ST, Connelly JP, Pruett-Miller SM, Roussel MF, Rakheja D, Tillman HS, Potts PR, Fon Tacer K. Melanoma antigens in pediatric medulloblastoma contribute to tumor heterogeneity and species-specificity of group 3 tumors. Acta Neuropathol Commun. 2025 Jul 28;13(1):164. doi: 10.1186/s40478-025-02055-3.
PubMed 40721826

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Chemo-immunotherapy Using Ibrutinib Plus Indoximod for Patients With Pediatric Brain Cancer
Ependymoma, Medulloblastoma

All Medulloblastoma trials

Study at a glance

From the registry record, last updated by the sponsor on 27 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase II Trial of the Immune Checkpoint Inhibitor Nivolumab in Patients With Recurrent Select Rare CNS Cancers
ClinicalTrials.gov ID: NCT03173950
Acronym / sponsor ID: 170102
Conditions: Medulloblastoma, Ependymoma, Pineal Region Tumors, Choroid Plexus Tumors, Atypical/Malignant Meningioma
Keywords: Immunotherapy, Anti-PD-1 Antibody, Brain Tumors, MDASI-BT, Spinal Cord Tumors
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Support was withdrawn from study resulting in early termination of study. Investigator had to close study due to no drug supply.
Enrolment: 136 participants (actual)
Lead sponsor: National Cancer Institute (NCI)US National Institutes of Health
Study start: 13 Jul 2017 (actual)
Primary completion: 23 Jun 2025 (actual)
Study completion: 23 Jun 2025 (actual)
First posted: 2 Jun 2017 (actual)
Results: Posted 18 Aug 2026

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Background:

Objectives:

To learn if stimulating the immune system using the drug nivolumab can shrink tumors in people with rare CNS (brain or spine) tumors or increase the time it takes for these tumors to grow or spread.

Eligibility:

Adults whose rare CNS tumor has returned.

Design:

Individuals will be screened:

Heart and blood tests
Physical and neurological exam
Hepatitis tests
Pregnancy test
Magnetic resonance imaging (MRI). They will lay in a machine that takes pictures.
Tumor tissue sample. This can be from a previous procedure.

At the start of the study, participants will have blood tests. They will answer questions about their symptoms and their quality of life.

Individuals will get nivolumab in a vein every 2 weeks for up to 64 weeks.

Individuals will have monthly blood tests. Every other month they will have an MRI and a neurologic function test. They will also answer questions about their quality of life.

Genetic tests will be done on individuals' tumor tissue. Individuals will be contacted if any clinically important results are found.

After treatment ends, individuals will be monitored for up to 5 years. They will have a series of MRIs and neurological function tests. They will be asked to report any symptoms they experience....

Detailed description

Background:

There are more than 130 identified primary tumors of the central nervous system (CNS). Most have an annual incidence of less than 1000 in the United States.
Given the rarity of each of the tumors listed above, there is a paucity of proven therapies. Most of these neoplasms are treated with maximum surgical resection followed by treatment with external beam radiotherapy. With few exceptions (medulloblastoma, adult ependymoma), there are no effective systemic regimens and even in chemotherapy sensitive disease, most patients with recurrence eventually have no remaining salvage treatments available.
In the setting of this unmet need, we propose to create a basket protocol that will evaluate the efficacy of the programmed cell death protein 1 (PD-1) inhibitor, nivolumab, in patients with refractory rare central nervous system neoplasms.
This study seeks to establish effective therapies at recurrence in patients with rare CNS tumors. We hypothesize that this therapy will improve progression free survival and/or objective responses.
It will be important to determine whether any determined survival benefit is associated with improvements in symptoms or does a worsening of symptoms offset the increase in survival. Precedence exists for measuring non-therapeutic endpoints in oncology research, and specifically in studies evaluating therapeutic benefit in patients with CNS tumors. There have been efforts in neuro-oncology to evaluate secondary endpoints using validated instruments as an additional indicator of benefit. The M.D. Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT) and Spine Tumor Module (MDASI-SP) allow for the self-reporting of symptom severity and interference with daily activities for patients with either brain or spinal cord tumors. The availability of validated instruments provides an opportunity to prospectively assess the impact of treatment, both positive and negative on patients.

Objective:

Eligibility:

Documented recurrent or progressive disease that corresponds to one of the tumors eligible for testing.
Age >= 18 years of age.
Karnofsky Performance >= 70%.
Tumor tissue available for central review to confirm morphologic diagnosis
Tumor tissue or slides must be available for central molecular and immune profiling.

Design:

This is an open label phase II clinical trial. Patients will be treated with the immune checkpoint inhibitor, nivolumab, at a standard dose of 240 mg intravenously every 2 weeks (+/- 3 days) for cycles 1 through 2, then doses of 480 mg every 4 weeks (+/- 3 days) for a total of 14 additional doses (cycles). A maximum of 18 treatments will be given (64 weeks).
A cycle will be defined as 4 weeks and patients will undergo efficacy assessments using MR imaging (and/or other imaging tests if applicable) every 2 cycles. Toxicity assessments will occur before the initiation of each cycle and patient outcomes measures (PROs) will be completed at the time of each imaging study (every 2 cycles) but prior to the patient being informed of the imaging results.
After completion of the planned treatment course or if treatment was stopped because of toxicity, patients will undergo imaging evaluations and PRO measurements every 8 weeks (or 2 months) for one year, then every 3 months for the next year, then every 4 months for the next year and then every 6 months while the patient remains on the protocol. Patients off treatment because of disease progression will not undergo future imaging or PRO assessments on this protocol.
Bayesian Optimal Phase 2 design (BOP2), will be used to conduct this phase II trial in patients with a variety of recurrent, refractory primary central nervous system tumors.
The study will be comprised of 2 disease cohorts: heavily pretreated (defined as having received 3 or more prior therapies) and non-heavily pretreated (defined as having received up to 2 prior therapies). Each cohort will be evaluated independently for efficacy.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Arm 1/Experimental Therapy - Nivolumab	Experimental	Drug: Nivolumab, Diagnostic Test: EKG, Diagnostic Test: MRI Brain and/or spine, Diagnostic Test: Body CT Scan, Other: MDASI-BT, Other: MDASI-SPIndividuals will receive nivolumab at standard dose of 240 mg intravenous (IV) every 2 weeks for cycles 1 through 2, then doses of 480 mg every 4 weeks for a total of 14 additional doses.

Who may qualify

Ages: 18 to 99 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (22 listed)

Histopathologically proven diagnosis of Ependymoma, Medulloblastoma, Parenchymal Pineal Region Tumors (Pineoblastoma, Pineocytoma, Pineal Tumor of Intermediate Differentiation, Papillary Tumor of the Pineal Region), Choroid Plexus Tumors (Carcinoma, Papilloma, Atypical Papilloma), Histone Mutated Gliomas, Gliomatosis Cerebri, Atypical Teratoid/Rhabdoid Tumor (ATRT), Malignant/Atypical Meningioma*, Gliosarcoma or Primary CNS Sarcoma, Pleomorphic Xanthoastrocytoma (PXA) and Anaplastic Pleomorphic Xanthoastrocytoma (APXA), and tumors formerly known as Primitive Neuro-Ectodermal Tumors (Embryonal Tumor with Multilayered Rosettes, Medulloepithelioma, Central Nervous System (CNS) Neuroblastoma, CNS Ganglioneuroblastoma, CNS Embryonal Tumor NOS; and tumor entities emerging from methylation profiling of CNS-PNETs: CNS neuroblastoma with Forkhead box protein R2 (FOXR2) activation, CNS Ewing sarcoma family tumor with CIC alteration, CNS high-grade neuroepithelial tumor with meningioma 1 (MN1) alterations, and CNS high-grade neuroepithelial tumor with BCOR alteration) prior to registration.
Individuals with extra CNS metastases from meningioma will be eligible even if pathology review fails to demonstrate high grade features on available tumor samples.
The tumor tissue (e.g., block or 20 unstained slides) must be available to be sent for immunophenotyping by National Cancer Institute (NCI) Laboratory of Pathology.
Individuals must have progressive tumor growth after having received established standard of care and/or other experimental treatments for their newly diagnosed or recurrent disease. Individuals will be enrolled into 2 different cohorts (cohort 1 or heavily pretreated; cohort 2 or not heavily pretreated).
Age >= 18

Key exclusion criteria (25 listed)

Individuals who are receiving any other investigational agents.
Prior use of an immunotherapy such as (but not limited to) a vaccine therapy, dendritic cell vaccine, other checkpoint inhibitors, or intracavitary or convectional enhanced delivery of chemotherapy.
Prior or concurrent malignancy unless its natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen.
Severe, active co-morbidity defined as follows:
Individuals with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids, should be excluded. These include but are not limited to individuals with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome or chronic inflammatory demyelinating polyneuropathyI (CIDP), myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and individuals with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should be excluded because of the risk of recurrence or exacerbation of disease.

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
NivolumabAlso: OpdivoIndividuals will receive nivolumab at standard dose of 240 mg intravenous (IV) every 2 weeks for cycles 1 through 2, then doses of 480 mg every 4 weeks for a total of 14 additional doses.	Drug	Arm 1/Experimental Therapy - Nivolumab
EKGAlso: ElectrocardiogramScreening/baseline.	Diagnostic test	Arm 1/Experimental Therapy - Nivolumab
MRI Brain and/or spineAlso: Magnetic resonance imaging brain and/or spineScreening/baseline.	Diagnostic test	Arm 1/Experimental Therapy - Nivolumab
Body CT ScanAlso: Body computed tomographyScreening/baseline.	Diagnostic test	Arm 1/Experimental Therapy - Nivolumab
MDASI-BTAlso: M.D. Anderson Symptom Inventory Brain Tumor (MDASI-BT)Screening/baseline. During active treatment and post therapy follow up.	Other	Arm 1/Experimental Therapy - Nivolumab
MDASI-SPAlso: M.D. Anderson Symptom Inventory Spine Tumor (MDASI-SP)Screening/baseline. During active treatment and post therapy follow up.	Other	Arm 1/Experimental Therapy - Nivolumab

Primary outcome

Disease Control Rate (Complete Response (CR) + Partial Response (PR) or Durable Stable Disease (SD) for 6 Months Measured in a Variety of Recurrent Refractory Primary Central Nervous System Tumors Reported With Standard Deviation
Time frame: From cycle one Day 1 of the treatment through the end of treatment, up to 64 weeks
Disease control rate (DCR) measured in a variety of recurrent refractory primary central nervous system tumors. DCR is defined as a confirmed CR/PR or durable stable disease (SD) for 6 months assessed by the Immunotherapy Response Assessment Neuro-Oncology (iRANO) criteria. Complete Response is complete disappearance of all enhancing measurable and non-measurable disease sustained for at least 4 weeks. Partial Response is ≥ 50% decrease compared to baseline in the sum of products of perpendicular diameters of all measurable enhancing lesions sustained for at least 4 weeks. Durable stable disease does not qualify for CR, PR or progression (>25% increase in the sum of the products of perpendicular diameters of enhancing lesions (over best response [smallest tumor size] or baseline if no decrease) on stable or increasing doses of corticosteroids. A single value was calculated (e.g. summed or averaged) by
Disease Control Rate (Complete Response (CR) + Partial Response (PR) or Durable Stable Disease (SD) for 6 Months Measured in a Variety of Recurrent Refractory Primary Central Nervous System Tumors Reported With a 95% Confidence Interval
Time frame: From cycle one Day 1 of the treatment through the end of the treatment, up to 64 weeks
Disease control rate (DCR) measured in a variety of recurrent refractory primary central nervous system tumors. DCR is defined as a confirmed CR/PR or durable stable disease (SD) for 6 months assessed by the Immunotherapy Response Assessment Neuro-Oncology (iRANO) criteria. Complete Response is complete disappearance of all enhancing measurable and non-measurable disease sustained for at least 4 weeks. Partial Response is ≥ 50% decrease compared to baseline in the sum of products of perpendicular diameters of all measurable enhancing lesions sustained for at least 4 weeks. Durable stable disease does not qualify for CR, PR or progression (i.e., >25% increase in the sum of the products of perpendicular diameters of enhancing lesions (over best response [smallest tumor size] or baseline if no decrease) on stable or increasing doses of corticosteroids. A single value was calculated (e.g. summed or averaged) by
Progression Free Survival (PFS)
Time frame: From cycle one Day 1 of the treatment through the end of the treatment, up to 64 weeks
PFS is defined as the date of on-study to the date of disease progression or death, estimated with the Kaplan-Meier method and reported with a 95% confidence interval. Response was assessed by the Immunotherapy Response Assessment Neuro-Oncology (iRANO) criteria and estimated using the Kaplan-Meier method. Progressive Disease is >25% increase in sum of the products of perpendicular diameters of enhancing lesions (over best response [smallest tumor size] or baseline if no decrease) on stable or increasing doses of corticosteroids.
Progression Free Survival at 6 Months With 95% Confidence Interval
Time frame: 6 months after the initiation of treatment, up to 24 weeks
PFS-6 is the rate of durable Stable Disease lasting at least 6 months defined from the day of study entry until imaging is confirmed to show disease progression reported with a 95% confidence interval based on the Brookmeyer-Crowley method. Response was assessed by the Immunotherapy Response Assessment Neuro-Oncology (iRANO) criteria and estimated using the Kaplan-Meier method. Progressive Disease is >25% increase in sum of the products of perpendicular diameters of enhancing lesions (over best response [smallest tumor size] or baseline if no decrease) on stable or increasing doses of corticosteroids.

7 secondary outcomes

Overall Survival (OS)
Time frame: Time from the study entry and after initiation of nivolumab to participants death, up to 5 years
Mean Symptom Burden Severity and Interference Using the MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT) and MD Anderson Symptom Inventory-Spine Tumor (MDASI-SP) Module Reported With a 95% Confidence Interval, at Each Time Point
Time frame: Baseline (Up to 14 days prior to treatment), and at time of imaging - cycle 2, 4, 6, 8, 10, and 12 (one cycle = 4 weeks)
Mean Symptom Burden Severity & Interference Using the MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT) & MD Anderson Symptom Inventory-Spine Tumor (MDASI-SP) Module Reported With Standard Deviation(SD) at Each Time Point
Time frame: Baseline (up to 14 days prior to treatment), and at time of imaging - cycle 2, 4, 6, 8, 10, or 12 (one cycle = 4 weeks)
Mean Symptom Burden Severity and Interference Using the MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT) and MD Anderson Symptom Inventory-Spine Tumor (MDASI-SP) Between Responders and Non-responders Reported With 95% Confidence Interval
Time frame: Two possible timepoints dependent on response status. Non-responders: determined by whether disease progression occurred prior to or at cycle 6 or not. Responders: cycle 6. One cycle= 4 weeks/participants who did not have disease progression by cycle 6.
Mean Symptom Burden Severity and Interference Using the MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT) and MD Anderson Symptom Inventory-Spine Tumor (MDASI-SP) Between Responders and Non-responders Reported With Standard Deviation
Time frame: Two possible timepoints dependent on response status. Non-responders: determined by whether disease progression occurred prior to or at cycle 6 or not. Responders: cycle 6. One cycle= 4 weeks/participants who did not have disease progression by cycle 6.
Mean Change Scores in Symptom Burden Severity and Interference Using the MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT) and MD Anderson Symptom Inventory-Spine Tumor (MDASI-SP) Module Between Baseline and Even-numbered Cycle
Time frame: Between Baseline (up to 14 days prior to treatment) and at time of imaging - cycle 2, 4, 6, 8, 10, and 12 (one cycle = 4 weeks)
Number of Grades 1, 2, 3, 4, and/or 5 Treatment Related Serious and/or Non-serious Adverse Events and Type
Time frame: Adverse Events were monitored/assessed from the first study intervention, Study Day 1 through 100 days after the study agent was last administered, up to 5 years

Results and safety

Results posted to the registry on 18 Aug 2026, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Cohort 1- Heavily Pre-Treated	76	42
Cohort 2 - Non-Heavily Pre-Treated	30	14
Participants Enrolled Who Were Not Treated OR Completed Treatment Cycles	30	0

Primary outcome: Disease Control Rate (Complete Response (CR) + Partial Response (PR) or Durable Stable Disease (SD) for 6 Months Measured in a Variety of Recurrent Refractory Primary Central Nervous System Tumors Reported With Standard Deviation

Time frame: From cycle one Day 1 of the treatment through the end of treatment, up to 64 weeks. Mean (Standard Deviation). Unit: Proportion of participants

Measure	Cohort 1- Heavily Pre-Treated n = 73	Cohort 2 - Non-Heavily Pre-Treated n = 29	Participants Enrolled Who Were Not Treated OR Completed Treatment Cycles n = 0
Value	0.219 (0.048)	0.379 (0.09)	–

Population analysed: 102/136 participants were analyzed because 19 participants were ineligible, 1 pursued other treatment, 1 withdrew consent and decided not to participate, 9 declined to participate before treatment started (after consent) ,1 withdrew consent and decided not to participate in cohort 2 and 3 did not complete a minimum of one cycle in cohort 1.

Primary outcome: Disease Control Rate (Complete Response (CR) + Partial Response (PR) or Durable Stable Disease (SD) for 6 Months Measured in a Variety of Recurrent Refractory Primary Central Nervous System Tumors Reported With a 95% Confidence Interval

Time frame: From cycle one Day 1 of the treatment through the end of the treatment, up to 64 weeks. Number (95% Confidence Interval). Unit: percentage of participants

Measure	Cohort 1- Heavily Pre-Treated n = 73	Cohort 2 - Non-Heavily Pre-Treated n = 29	Participants Enrolled Who Were Not Treated OR Completed Treatment Cycles n = 0
Value	21.9 (13.1 to 33.1)	37.9 (20.7 to 57.7)	–

Primary outcome: Progression Free Survival (PFS)

Time frame: From cycle one Day 1 of the treatment through the end of the treatment, up to 64 weeks. Median (95% Confidence Interval). Unit: Days

Measure	Cohort 1- Heavily Pre-Treated n = 76	Cohort 2 - Non-Heavily Pre-Treated n = 29	Participants Enrolled Who Were Not Treated OR Completed Treatment Cycles n = 0
Value	56.5 (55 to 111)	133 (110 to 223)	–

Population analysed: 105/136 participants were analyzed because 19 participants were ineligible, 1 pursued other treatment, 2 withdrew consent and decided not to participate, and 9 declined to participate before treatment started (after consent).

Primary outcome: Progression Free Survival at 6 Months With 95% Confidence Interval

Time frame: 6 months after the initiation of treatment, up to 24 weeks. Median (95% Confidence Interval). Unit: Percentage of participants

Measure	Cohort 1- Heavily Pre-Treated n = 73	Cohort 2 - Non-Heavily Pre-Treated n = 29	Participants Enrolled Who Were Not Treated OR Completed Treatment Cycles n = 0
Value	21.9 (13.1 to 33.1)	37.9 (20.7 to 57.7)	–

7 secondary outcomes are reported in the full results.

Adverse events

Time frame: All-Cause Mortality was monitored/documented throughout the study and up to 5 years post treatment &/or until early termination of the study. Document adverse events from the first study intervention, Study Day 1 through 100 days after the study agent was last administered. Adverse events that are serious need to be recorded in 100 days. Beyond 100 days after the last intervention, only adverse events which are serious and related to the study intervention need to be recorded for up to 5 years.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Cohort 1- Heavily Pre-Treated	43 of 76 (56.6%)	70 of 76 (92.1%)	42 of 76
Cohort 2 - Non-Heavily Pre-Treated	13 of 30 (43.3%)	29 of 30 (96.7%)	10 of 30
Participants Enrolled Who Were Not Treated OR Completed Treatment Cycles	0 of 30 (0%)	0 of 30 (0%)	1 of 30

Limitations and caveats (from the sponsor): 11 participating sites started/3completed:National Institutes of Health Clinical Center, Northwestern University, University of Texas MDAnderson Cancer Center. Sites contributed to data/closed early to enrollment due to poor accrual:University of Pittsburgh Medical Center, University of California San Diego, University of California Irvine, Orlando Health, Washington University in St. Louis, NorthShore University HealthSystem, The Ohio States University, and Medical University of South Carolina.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 27 Oct 2026.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 20425040Gilbert MR, Ruda R, Soffietti R. Ependymomas in adults. Curr Neurol Neurosci Rep. 2010 May;10(3):240-7. doi: 10.1007/s11910-010-0109-3.
Background: PubMed 26545842Okada H, Weller M, Huang R, Finocchiaro G, Gilbert MR, Wick W, Ellingson BM, Hashimoto N, Pollack IF, Brandes AA, Franceschi E, Herold-Mende C, Nayak L, Panigrahy A, Pope WB, Prins R, Sampson JH, Wen PY, Reardon DA. Immunotherapy response assessment in neuro-oncology: a report of the RANO working group. Lancet Oncol. 2015 Nov;16(15):e534-e542. doi: 10.1016/S1470-2045(15)00088-1.
Background: PubMed 27525433Daud AI, Loo K, Pauli ML, Sanchez-Rodriguez R, Sandoval PM, Taravati K, Tsai K, Nosrati A, Nardo L, Alvarado MD, Algazi AP, Pampaloni MH, Lobach IV, Hwang J, Pierce RH, Gratz IK, Krummel MF, Rosenblum MD. Tumor immune profiling predicts response to anti-PD-1 therapy in human melanoma. J Clin Invest. 2016 Sep 1;126(9):3447-52. doi: 10.1172/JCI87324. Epub 2016 Aug 15.
Derived from this study: PubMed 40721826Collins RRJ, Florke Gee RR, Tozandehjani S, Bayat T, Hoyos Sanchez MC, Gutierrez JSS, Breznik B, Lee AK, Peters ST, Connelly JP, Pruett-Miller SM, Roussel MF, Rakheja D, Tillman HS, Potts PR, Fon Tacer K. Melanoma antigens in pediatric medulloblastoma contribute to tumor heterogeneity and species-specificity of group 3 tumors. Acta Neuropathol Commun. 2025 Jul 28;13(1):164. doi: 10.1186/s40478-025-02055-3.
NIH Clinical Center Detailed Web PageLink provided by the sponsor.
Individual participant dataSharing planned: Yes. All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request. In addition, all large-scale genomic sequencing data will be shared with subscribers to the database of Genotypes and Phenotypes (dbGaP).

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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.

Kevin Camphausen, M.D. principal investigator

National Cancer Institute (NCI)

3 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Nivolumab, EKG and MRI Brain and/or spine in people with Medulloblastoma and Ependymoma, run by National Cancer Institute (NCI) at 3 sites 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 22 inclusion and 25 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: stopped early, as of the sponsor's last update on 27 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 Aug 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Disease Control Rate (Complete Response (CR) + Partial Response (PR) or Durable Stable Disease (SD) for 6 Months Measured in a Variety of Recurrent Refractory Primary Central Nervous System Tumors Reported With Standard Deviation (time frame: From cycle one Day 1 of the treatment through the end of treatment, up to 64 weeks). The study lists 4 primary outcomes in all. 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 NCT03173950, which also lists 4 linked publications.

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 27 Oct 2026.