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

NCT03173950 | Completed Phase 2 FDA Drug

• 2 other identifiers: 17010217-C-0102
• Study Type: interventional
• Target: 133
• 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
• 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 (2)

• objective response

  Rate of achieving a confirmed Complete Response/Partial Response (confirmed by imaging one month later)

  end of treatment

• progression free survival rate

  Rate of durable Stable Disease lasting at least 6 months (PFS-6)

  6 months after end of treatment

Study Arms (1)

1/Experimental Therapy

EXPERIMENTAL

Individuals will receive nivolumab at standard dose of 240 mg 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

Interventions

Nivolumab DRUG

Individuals will receive nivolumab at standard dose of 240 mg IV every 2 weeks for cycles 1 through 2, then doses of 480 mg every 4 weeks for a total of 14 additional doses

1/Experimental Therapy

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, 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, CNS Neuroblastoma, CNS Ganglioneuroblastoma, CNS Embryonal Tumor NOS; and tumor entities emerging from methylation profiling of CNS-PNETs: CNS neuroblastoma with FOXR2 activation, CNS Ewing sarcoma family tumor with CIC alteration, CNS high-grade neuroepithelial tumor with 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 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 CBC/differential within 14 days prior to Step 2 registration defined as follows:
• Absolute neutrophil count \>= 1,500 cells/mm3;
• Platelet count \>= 100,000 cells/mm3
• 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:
• 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 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 (3)

• 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

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

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

Study Officials

• Byram H Ozer, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

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: June 29, 2025

Record last verified: 2025-06-26

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 GDS plan for as long as database is active.
• Access Criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI. Genomic data are made available via dbGaP through requests to the data custodians.

Locations

US (3)