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

NCT03173950 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: 17010217-C-0102
• Study Type: interventional
• Target: 136
• Locations: 1 country
• Sites: 3

Brief 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. 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....

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

Outcome Measures

Primary Outcomes (4)

• 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

  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

  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.

  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.

  6 months after the initiation of treatment, up to 24 weeks

Secondary Outcomes (7)

• Overall Survival (OS)

  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

  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

  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

  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

  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.

Other Outcomes (1)

• Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0).

  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

Study Arms (1)

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.

Drug: Nivolumab; Diagnostic Test: EKG; Diagnostic Test: MRI Brain and/or spine; Diagnostic Test: Body CT Scan; Other: MDASI-BT; Other: MDASI-SP

Interventions

Nivolumab DRUG

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.

Also known as: Opdivo

Arm 1/Experimental Therapy - Nivolumab

EKG DIAGNOSTIC_TEST

Screening/baseline.

Also known as: Electrocardiogram

Arm 1/Experimental Therapy - Nivolumab

MRI Brain and/or spine DIAGNOSTIC_TEST

Screening/baseline.

Also known as: Magnetic resonance imaging brain and/or spine

Arm 1/Experimental Therapy - Nivolumab

Body CT Scan DIAGNOSTIC_TEST

Screening/baseline.

Also known as: Body computed tomography

Arm 1/Experimental Therapy - Nivolumab

MDASI-BT OTHER

Screening/baseline. During active treatment and post therapy follow up.

Also known as: M.D. Anderson Symptom Inventory Brain Tumor (MDASI-BT)

Arm 1/Experimental Therapy - Nivolumab

MDASI-SP OTHER

Screening/baseline. During active treatment and post therapy follow up.

Also known as: M.D. Anderson Symptom Inventory Spine Tumor (MDASI-SP)

Arm 1/Experimental Therapy - Nivolumab

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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:

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (3)

Northwestern University

Chicago, Illinois, 60611, United States

Location

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

UT MD Anderson Cancer Center

Houston, Texas, 77030-4096, United States

Location

Related Publications (4)

• 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.

  PMID: 20425040 BACKGROUND

• 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.

  PMID: 26545842 BACKGROUND

• 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.

  PMID: 27525433 BACKGROUND

• 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.

  PMID: 40721826 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Medulloblastoma; Ependymoma; Pinealoma; Choroid Plexus Neoplasms; Meningioma; Brain Neoplasms; Spinal Cord Neoplasms

Interventions

Nivolumab; Electrocardiography

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors, Primitive; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Cerebral Ventricle Neoplasms; Neoplasms, Vascular Tissue; Meningeal Neoplasms; Spinal Cord Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Heart Function Tests; Diagnostic Techniques, Cardiovascular; Diagnostic Techniques and Procedures; Diagnosis; Electrodiagnosis

Limitations and Caveats

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.

Results Point of Contact

• Title: Dr. Jing Wu
• Organization: National Cancer Institute

jing.wu3@nih.gov

240-760-6036

Study Officials

• Jing Wu, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 31, 2017
• First Posted: June 2, 2017
• Study Start: July 13, 2017
• Primary Completion: June 23, 2025
• Study Completion: June 23, 2025
• Last Updated: August 18, 2026
• Results First Posted: August 18, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely. Genomic data are available once genomic data are uploaded per protocol Genomic Data Sharing (GDS) plan for as long as database is active.
• Access Criteria: Clinical data will be made available via subscription to Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI). Genomic data are made available via the database of Genotypes and Phenotypes (dbGaP) through requests to the data custodians.

Locations

US (3)