Cytokine Microdialysis for Real-Time Immune Monitoring in Glioblastoma Patients Undergoing Checkpoint Blockade

NCT03493932 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 18007718-N-0077
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 2

Brief Summary

Background: Glioblastoma (GBM) brain tumors almost always return after treatment. When that happens the tumor can never completely be removed by surgery, so most people also receive drugs. Researchers want to see if combining the drugs nivolumab and BMS-986016 may help. Objectives: To study how nivolumab affects the brain s immune system in people who have had glioblastoma brain tumors return. To study how nivolumab and BMS-986016 affect brain tumors. Eligibility: Adults age 18 and older who have had a return of GBM Design: Participants will be screened with: Medical history Physical exam Cheek swab Heart, blood and urine tests Chest x-ray Magnetic resonance imaging (MRI) brain scan. Participants will lie on a table that slides in and out of a cylinder in a strong magnetic field. A contrast agent will be injected in an arm vein. Participants will stay in the hospital. They will: Have surgery. A tube will be inserted into the back. Brain tumor and bone marrow samples will be taken. Tubes will be inserted into the brain. Have a computed tomography brain scan. Stay in Intensive Care (ICU) 7 days. Fluid from the brain and back will be collected every few hours. In the ICU, participants will get nivolumab by IV for 30 minutes. Have surgery to remove the tubes. Have standard surgery to remove as much of the GBM as possible. Bone marrow will be removed. After leaving the hospital, participants will have visits every 2 weeks to get the study drugs by IV and have physical exams and blood tests. Participants will have a brain MRI once a month. ...

Conditions

Glioblastoma

Keywords

Glioblastoma; Glioma; Brain Tumor; Immune Therapy; Checkpoint Inhibition

Outcome Measures

Primary Outcomes (3)

• Increase of Interferon Gamma Levels

  The proportion of patients that have a rise in interferon gamma levels within the tumor microenvironment of 4 pg/ml or higher before the first dose of Nivolumab as compared to the 5th day after treatment with Nivolumab.

  Day 8

• Microdialysis Catheter

  The number of patients with any adverse events that are directly attributable to placement of the microdialysis catheter. Specifically, intracranial hemorrhage, intracranial infection, wound infection, or new neurological deficit attributable to location of microdialysis catheter placement were to be captured

  Day 8

• Drug Safety

  The safety of the combination of nivolumab and BMS-986016 in recurrent glioblastoma patients

  Day 8

Study Arms (1)

Nivolumab and BMS-986016

EXPERIMENTAL

Recurrent Glioblastoma patients

Drug: Nivolumab; Drug: BMS-986016

Interventions

Nivolumab DRUG

OPDIVO is a human programmed death receptor-1 (PD-1) blocking antibody indicated for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor.

Nivolumab and BMS-986016

BMS-986016 DRUG

Anti-Lymphocyte Activation Gene-3 antibody undergoing clinical evaluation by Bristol-Myers Squibb

Nivolumab and BMS-986016

Eligibility Criteria

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

You may qualify if:

• To be eligible for entry into the study, a candidate must meet all the following criteria:
• Be 18 years of age or older.
• Have recurrent glioblastoma that is amenable to surgical resection.
• Agree to undergo brain surgery.
• Are eligible for 03-N-0164 "Evaluation and Treatment of Neurosurgical Disorders" protocol 5. Willing and able to appoint a durable power of attorney.
• Willing and able to appoint a durable power of attorney
• Are willing to use an effective method of contraception during the clinical study as defined on the consent and for 24 weeks (for women) or 33 weeks (for men) after the last dose of the study drug.

You may not qualify if:

• Candidates will be excluded if they:
• Have a bleeding disorder that cannot be corrected before invasive testing or surgery, or other medical conditions that would make surgery unsafe, such as lung or cardiac disease that would render them unable to tolerate the risk of general anesthesia, or severe immunodeficiency.
• Has a known additional malignancy that is progressing or requires active treatment within 3 years of registration. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
• Are pregnant or breastfeeding
• Cannot have an MRI scan.
• Are claustrophobic
• Are not able to lie on their back for up to 60 minutes
• Have primary CNS lymphoma.
• Has received systemic immunosuppressive treatments, aside from systemic corticosteroids (such as methotrexate, chloroquine, azathioprine, etc) within six months of registration
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
• Have a significant cardiac history, such as 2 or more MIs OR 2 or more coronary revascularization procedures.
• Have abnormal findings on ECG such as prolonged QT interval, T-wave abnormalities or arrhythmia. Abnormal findings on ECG will prompt an evaluation by a cardiologist prior to enrollment in the study
• Are currently undergoing treatment with another therapeutic agent for glioblastoma
• Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti- Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
• Have an ejection fraction less than 50% on screening echocardiogram

Sponsors & Collaborators

• National Institute of Neurological Disorders and Stroke (NINDS): lead

Study Sites (2)

Emory University

Atlanta, Georgia, 30322, United States

Location

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Glioblastoma; Glioma; Brain Neoplasms

Interventions

Nivolumab; relatlimab

Condition Hierarchy (Ancestors)

Astrocytoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; 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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Edjah K. Nduom, MD, FAANS
• Organization: Emory University

edjah.k.nduom@emory.edu

404-778-5770

Study Officials

• Sadhana Jackson, M.D.

  National Institute of Neurological Disorders and Stroke (NINDS)

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 10, 2018
• First Posted: April 11, 2018
• Study Start: September 24, 2018
• Primary Completion: April 21, 2023
• Study Completion: June 27, 2023
• Last Updated: July 24, 2024
• Results First Posted: July 24, 2024

Record last verified: 2023-09

Locations

US (2)