Ignite Creation Date:
2025-12-24 @ 10:00 PM
Ignite Modification Date:
2025-12-25 @ 7:37 PM
Study NCT ID:
NCT03493932
Status:
COMPLETED
Last Update Posted:
2024-07-24
First Post:
2018-04-10
Is NOT Gene Therapy:
False
Has Adverse Events:
True
Brief Title:
Cytokine Microdialysis for Real-Time Immune Monitoring in Glioblastoma Patients Undergoing Checkpoint Blockade
Sponsor:
National Institute of Neurological Disorders and Stroke (NINDS)
Organization:
Study Overview
Official Title:
Cytokine Microdialysis For Real Time Immune Monitoring in Glioblastoma Patients Undergoing Checkpoint Blockade
Status:
COMPLETED
Status Verified Date:
2023-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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.
...
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.
...
Detailed Description:
Objective
This protocol is being performed to 1) characterize the clinical and 2) immunological response of patients with recurrent glioblastoma to treatment with Nivolumab, together with an anti-Lag-3 antibody, BMS-986016, and to evaluate the safety of brain tumor microdialysis in this patient population.
Study Population
10 patients (total, after replacement for any dropout), 18 years old and older with recurrence of glioblastoma after standard treatment of surgery, chemotherapy, and radiation.
Study Design
Patients will be screened by study neurosurgeons or neuro-oncologists to verify their confirmed or likely diagnosis of a recurrent glioblastoma. Patients will be offered standard of care therapy, including repeat surgery and/or recommendations for chemotherapeutic agents and other trials. If the patients are deemed to be surgical candidates for their potential recurrence, they will be enrolled in the trial. Enrolled patients will then undergo a stereotactic brain biopsy. If a frozen section confirms a diagnosis of recurrent glioblastoma, two microdialysis catheters will be placed in the brain after the biopsy, and a lumbar drain will also be placed. These microdialysis catheters will sample interstitial fluid in and around the brain tumor every 6 hours. We will collect blood and cerebral spinal fluid samples daily for comparison. After two days (Day 3), the patients will be given one dose of Nivolumab, 240mg IV. We will continue to collect samples every six hours from the microdialysis catheters and daily from blood and cerebral spinal fluid for 5 additional days, after which patients will undergo surgical resection of their tumors and removal of the microdialysis catheters and lumbar drain. Nivolumab, at a dose of 240mg IV over 30 minutes every 2 weeks, will be administered after surgery (starting on Day 17(+/- 2 days), two weeks after the first dose on Day 3) followed by BMS 986016, an anti-Lag-3 antibody at a dose of 80mg IV over 60 minutes, until the study neuroradiologist notes tumor progression on MRI or the patient experiences treatment toxicity. While on therapy with Nivolumab and BMS-986016, patients will be seen and examined every 2 weeks +/- two days for signs of toxicity. Patients will be followed for at least three months after the surgical procedure.
Outcome Measures
The primary outcome measures are the proportion of patients who have a measurable increase of interferon gamma levels in the brain tumor tissue after their first dose of Nivolumab as compared to the pre-treatment baseline, the safety of using brain tumor microdialysis to monitor response to immune modulators in patients with recurrent glioblastoma and the safety of the combination of Nivolumab and BMS-986016. Exploratory outcome measures include: 1) To determine the change in interferon gamma production within the tumor microenvironment and in the rest of the body from before and after therapy with the immune checkpoint inhibitor, nivolumab; 2) To evaluate the pathological response of the immune microenvironment of brain tumor tissue to the first dose of Nivolumab; 3) To evaluate the clinical response (progression free survival, overall survival) of recurrent glioblastoma patients to this treatment combination; 4) To describe the difference in survival between responders and non-responders on this treatment combination; 5) To examine the differences in the immune cells and secreted factors of the tumor environment as compared to the immune cells and secreted factors of the cerebral spinal fluid, blood and, potentially, bone marrow in response to this treatment.
This protocol is being performed to 1) characterize the clinical and 2) immunological response of patients with recurrent glioblastoma to treatment with Nivolumab, together with an anti-Lag-3 antibody, BMS-986016, and to evaluate the safety of brain tumor microdialysis in this patient population.
Study Population
10 patients (total, after replacement for any dropout), 18 years old and older with recurrence of glioblastoma after standard treatment of surgery, chemotherapy, and radiation.
Study Design
Patients will be screened by study neurosurgeons or neuro-oncologists to verify their confirmed or likely diagnosis of a recurrent glioblastoma. Patients will be offered standard of care therapy, including repeat surgery and/or recommendations for chemotherapeutic agents and other trials. If the patients are deemed to be surgical candidates for their potential recurrence, they will be enrolled in the trial. Enrolled patients will then undergo a stereotactic brain biopsy. If a frozen section confirms a diagnosis of recurrent glioblastoma, two microdialysis catheters will be placed in the brain after the biopsy, and a lumbar drain will also be placed. These microdialysis catheters will sample interstitial fluid in and around the brain tumor every 6 hours. We will collect blood and cerebral spinal fluid samples daily for comparison. After two days (Day 3), the patients will be given one dose of Nivolumab, 240mg IV. We will continue to collect samples every six hours from the microdialysis catheters and daily from blood and cerebral spinal fluid for 5 additional days, after which patients will undergo surgical resection of their tumors and removal of the microdialysis catheters and lumbar drain. Nivolumab, at a dose of 240mg IV over 30 minutes every 2 weeks, will be administered after surgery (starting on Day 17(+/- 2 days), two weeks after the first dose on Day 3) followed by BMS 986016, an anti-Lag-3 antibody at a dose of 80mg IV over 60 minutes, until the study neuroradiologist notes tumor progression on MRI or the patient experiences treatment toxicity. While on therapy with Nivolumab and BMS-986016, patients will be seen and examined every 2 weeks +/- two days for signs of toxicity. Patients will be followed for at least three months after the surgical procedure.
Outcome Measures
The primary outcome measures are the proportion of patients who have a measurable increase of interferon gamma levels in the brain tumor tissue after their first dose of Nivolumab as compared to the pre-treatment baseline, the safety of using brain tumor microdialysis to monitor response to immune modulators in patients with recurrent glioblastoma and the safety of the combination of Nivolumab and BMS-986016. Exploratory outcome measures include: 1) To determine the change in interferon gamma production within the tumor microenvironment and in the rest of the body from before and after therapy with the immune checkpoint inhibitor, nivolumab; 2) To evaluate the pathological response of the immune microenvironment of brain tumor tissue to the first dose of Nivolumab; 3) To evaluate the clinical response (progression free survival, overall survival) of recurrent glioblastoma patients to this treatment combination; 4) To describe the difference in survival between responders and non-responders on this treatment combination; 5) To examine the differences in the immune cells and secreted factors of the tumor environment as compared to the immune cells and secreted factors of the cerebral spinal fluid, blood and, potentially, bone marrow in response to this treatment.
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| 18-N-0077 | None | None | View |