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Trial record 4 of 12 for:    BMS-986016

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

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ClinicalTrials.gov Identifier: NCT03493932
Recruitment Status : Recruiting
First Posted : April 11, 2018
Last Update Posted : June 20, 2018
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )

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 22 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.


Condition or disease Intervention/treatment Phase
Glioblastoma Drug: Nivolumab Drug: BMS-986016 Phase 1

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), 22 years old and older with first 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 concurrently collect blood and cerebral spinal fluid samples 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 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, 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. Secondary 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 bone marrow in response to this treatment.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Cytokine Microdialysis for Real-Time Immune Monitoring in Glioblastoma Patients Undergoing Checkpoint Blockade
Estimated Study Start Date : June 25, 2018
Estimated Primary Completion Date : June 1, 2021
Estimated Study Completion Date : June 1, 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Nivolumab

Arm Intervention/treatment
Experimental: 1
Recurrent Glioblastoma patients
Drug: Nivolumab
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.

Drug: BMS-986016
Anti-Lymphocyte Activation Gene-3 antibody undergoing clinical evaluation by Bristol-Myers Squibb




Primary Outcome Measures :
  1. The primary outcome measure is 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 after the first dose, the safety of th... [ Time Frame: 5 Days ]

Secondary Outcome Measures :
  1. 1)change in IFNg in body 2)response of immune environment of brain tumor tissue to Nivolumab 3)To evaluate clinical response of pts 4)the difference in survival between responders and non-responders 5)differences in the immune cells and secreted... [ Time Frame: Study Completion ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   22 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

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

  1. Be 22 years of age or older.
  2. Have solitary 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.

6. Are not on steroids, or are on a stable (without an increase for the preceding 2 weeks) or decreasing dose of steroids

7. Are willing to use an effective method of contraception during the clinical study as defined on the consent and for 5 months (for women) or 7 months (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 or systemic cancer not related to a brain lesion.
  2. Are pregnant or breastfeeding
  3. Cannot have an MRI scan.
  4. Are claustrophobic
  5. Are not able to lie on their back for up to 60 minutes
  6. Have an absolute lymphocyte count less than 500
  7. Have multiple brain tumors, evidence of carcinomatous meningitis, gliomatosis cerebri, or primary CNS lymphoma.
  8. Have an unrelated autoimmune disease
  9. Have a significant cardiac history, such as 2 or more MIs OR 2 or more coronary revascularization procedures.
  10. 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
  11. Are currently undergoing treatment with another therapeutic agent for glioblastoma
  12. Have a history of having been treated with immune therapy
  13. Have an ejection fraction less than 50% on screening echocardiogram
  14. Have positive serology for HIV, HBV and HCV
  15. Have an active infection that requires systemic antibacterial, antiviral or antifungal therapy

    Less than 7 days prior to initiation of study drug therapy

  16. Have a history of transfer of autologous or allogeneic T cells
  17. Have cardiac Troponin T or I greater than 2 times the institutional upper limit of normal at screening
  18. 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.
  19. Cannot speak English or Spanish fluently

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03493932


Contacts
Contact: Gretchen C Scott, R.N. (301) 496-2921 SNBrecruiting@nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)    800-411-1222 ext TTY8664111010    prpl@cc.nih.gov   
Sponsors and Collaborators
National Institute of Neurological Disorders and Stroke (NINDS)
Investigators
Principal Investigator: Edjah K Nduom, M.D. National Institute of Neurological Disorders and Stroke (NINDS)

Additional Information:
Responsible Party: National Institute of Neurological Disorders and Stroke (NINDS)
ClinicalTrials.gov Identifier: NCT03493932     History of Changes
Other Study ID Numbers: 180077
18-N-0077
First Posted: April 11, 2018    Key Record Dates
Last Update Posted: June 20, 2018
Last Verified: April 2, 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) ):
Glioblastoma
Glioma
Brain Tumor
Immune Therapy
Checkpoint Inhibition

Additional relevant MeSH terms:
Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Nivolumab
Antineoplastic Agents