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

• Status: Active, not recruiting
• Trial end date: 2022-06-30
• Target enrollment: 0
• Participant gender: All

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.

...

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Neurological Disorders and Stroke (NINDS)
• Treatments: Nivolumab

Criteria

• INCLUSION CRITERIA:

To be eligible for entry into the study, a candidate must meet all the following criteria:

1. Be 18 years of age or older.

2. Have recurrent glioblastoma that is amenable to surgical resection.

3. Agree to undergo brain surgery.

4. Are eligible for 03-N-0164 "Evaluation and Treatment of Neurosurgical Disorders" protocol 5. Willing and able to appoint a durable power of attorney.

5. Willing and able to appoint a durable power of attorney

6. 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.

EXCLUSION CRITERIA:

Candidates will be excluded if they:

1. 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.

2. 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.

3. Are pregnant or breastfeeding

4. Cannot have an MRI scan.

5. Are claustrophobic

6. Are not able to lie on their back for up to 60 minutes

7. Have primary CNS lymphoma.

8. Has received systemic immunosuppressive treatments, aside from systemic corticosteroids (such as methotrexate, chloroquine, azathioprine, etc) within six months of registration

9. 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

10. Have a significant cardiac history, such as 2 or more MIs OR 2 or more coronary revascularization procedures.

11. 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

12. Are currently undergoing treatment with another therapeutic agent for glioblastoma

13. 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).

14. Have an ejection fraction less than 50% on screening echocardiogram

15. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies) at the time of enrollment

16. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected) at the time of enrollment.

17. Have an active infection that requires systemic antibacterial, antiviral or antifungal therapy Less than 7 days prior to initiation of study drug therapy

18. Have a history of transfer of autologous or allogeneic T cells

19. Have a history of solid organ or tissue transplants

20. Have cardiac Troponin T or I greater than 2 times the institutional upper limit of normal at screening

21. At the time of enrollment, lack of consent capacity due to cognitive impairment that would make them incapable of understanding the explanation of the procedures in this study. Cognitive capacity to consent will be determined at the time of enrollment. Patients with mental disorders or those patients who are cognitively impaired yet still retain consent capacity will not be excluded.

22. Cannot speak English or Spanish fluently

23. Patients that require dexamethasone greater than 4 mg/ day or equivalent of steroids