Clinical Trials

Patients with bleeding in the brain causing a type of stroke (intracerebral hemorrhage or ICH) may be eligible for this study.

• Participantsmust be 18 years or older

• Participants must have a confirmed diagnosis of cancermetastasized to the brain

Inclusion Criteria:

Exclusion Criteria:

Key eligibility criteria include:

• Diagnosis of newly diagnosed GBM or any malignant glioma with plan to initiate treatment with TTFields with or without systemic therapy, confirmed by the enrolling institution
• Able to self-administer topical interventions or has available another person who can apply the topical agents
• Treatment with TTF should be initiated within 7 days of planned initiation in this trial
• Age of at least 18 years old

All prospective patients will undergo screening tests to determine if they are eligible to take part in the study.

Note: This is only a partial list of eligibility criteria. Please contact the Robert H. Lurie Comprehensive Cancer Center of Northwestern University for complete screening information if you are interested in this clinical trial.

• INCLUSION CRITERIA:

• 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.

  *Patient 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.
• Participants must have progressive tumor growth after having received established standard of care and/or other experimental treatments for their newly diagnosed or recurrent disease. Participants will be enrolled into 2 different cohorts (cohort 1 or heavily pretreated; cohort 2 or not heavily pretreated
• Age greater than or equal to 18;
• Karnofsky performance status (Bullet) 70 within 14 days prior to Step 2 registration; Participants 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 greater than or equal to 1,500 cells/mm3;
  • Platelet count greater than or equal to 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 less than or equal to 30 mg/dl and
  • Serum creatinine less than or equal to 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:

  • Total bilirubin (except patients with Gilbert s Syndrome, who are eligible for the study but exempt from the total bilirubin eligibility criterion) less than or equal to 2.0 mg/dl and
  • ALT and AST less than or equal to 2.5x ULN
  • No active or chronic hepatitis infection. HCV antibody (for Hepatitis C) and Hepatitis B Surface antigen and Hepatitis B core antibody must be negative. This has been routinely incorporated into immunotherapy trials with checkpoint inhibitors because of concerns that the risk of treatment-induced hepatic injury is increased in the setting of active viral hepatitis.
• The patient must not be on a corticosteroid dose greater than physiologic replacement dosing defined as 30 mg of cortisone per day or its equivalent.

• The patient must provide study-specific informed consent prior to study entry. No Durable Power of Attorney or Next of Kin can provide initial consent.

  2.1.1.10 Participants must meet the below requirements regarding COVID-19 Status:

  2.1.1.10.1 Participants must be fully vaccinated for coronavirus disease 2019 (COVID-19) as defined by the Center for Disease Control guidance for patients who are immunocompromised. Participants must have received required vaccination(s) by the time of Step 2 registration and be considered fully immunized (typically 2 weeks after final vaccination) by the time of the initiation of treatment.

  2.1.1.10.2 Participants must have a negative COVID-19 test within 72 hours of the first dose of study drug. Patients who had documented COVID-19 infection within 90 days of treatment but are more than 20 days from infection do not need to be tested and are eligible if they fulfill the eligibility requirement regarding adequate vaccination.

  2.1.1.10.3 Vaccinated participants must agree to follow current guidance to protect themselves from exposure to COVID-19, such as wearing masks, social distancing, and maintaining good hand hygiene even after vaccination.

• The effects of nivolumab on the developing human fetus are unknown. For this reason, women of childbearing potential (WOCBP) must use appropriate method(s) of contraception. WOCBP should use an adequate method to avoid pregnancy for 5 months (30 days plus the time required for nivolumab to undergo five half-lives) after the last dose of investigational drug.

NOTE: Based on the evidence cited in Nivolumab IB ver. 20, given that nivolumab is not a genotoxic agent, and that relevant systemic concentrations sufficient to produce a risk of fetal toxicity are not expected in WOCBP partners from exposure to a male participant s seminal fluid, male study participants will not be required to use contraceptive measures and/or a latex or other synthetic condom during sexual activity with a WOCBP partner.

EXCLUSION CRITERIA:

10. Participants with contraindications to COVID-19 vaccination will not be eligible.

11. Participants unable to have MRIs.

Some of the eligibility criteria include:

· Radiographic confirmation of 1-4 brain metastases

· Participants must be 18 or older

· Known active or history of invasive non-central nervous system (CNS) primary cancer based on documented pathologic diagnosis within the past 3 years cancer based on documented pathologic diagnosis within the past 3 years

Note: This is only a partial list of eligibility criteria. Please contact the Robert H. Lurie Comprehensive Cancer Center of Northwestern University for complete screening information if you are interested in this clinical trial.

Inclusion Criteria:

• 22-75 years of age at screening
• Active moderate or severe RA, defined as at least 4/28 tender and 4/28 swollen joints
• Demonstrated an inadequate response, loss of response, or intolerance to 1 or more approved for rheumatoid arthritis biologic or targeted synthetic Disease-Modifying Anti-Rheumatic Drugs (DMARDs), including Janus kinase inhibitors (JAKi)
• Receiving treatment with at least 1 conventional synthetic DMARD for at least 12 weeks and on a continuous non-changing dose and route of administration for at least 4 weeks prior to Screening and able to continue the same stable dose through Week 12

Exclusion Criteria:

• Untreated or poorly controlled psychiatric illness or history of substance abuse
• Significant immunodeficiency due to underlying illness
• History of stroke or transient ischemic attack, or diagnosis of cerebrovascular fibromuscular dysplasia
• Clinically significant cardiovascular disease
• Neurological syndromes, including multiple sclerosis, Alzheimer's disease, or Parkinson's disease
• Uncontrolled fibromyalgia
• History of left or right carotid surgery
• History of unilateral or bilateral vagotomy, partial or complete splenectomy
• Recurrent vasovagal syncope episodes
• Current, regular use of tobacco products