Phase II Trial Evaluating the Association of Peripheral Blood Immunologic Response to Therapeutic Response to Adjuvant Treatment With Immune Checkpoint Inhibition (ICI) in Patients With Newly Diagnosed Glioblastoma or Gliosarcoma
Background: Glioblastoma (GBM) is a type of malignant glioma. These cancers are nearly always fatal. People who develop these cancers get aggressive treatments. But the tumors almost always recur. Researchers want to study people with newly diagnosed disease to learn more.
Objective: To study people with newly diagnosed GBM or gliosarcoma to look at the changes in immune cells in the blood of those who take ipilimumab and nivolumab, along with temozolomide.
Eligibility: Adults ages 18 and older with newly diagnosed GBM or gliosarcoma, who have had surgical removal of their tumor and have completed standard initial chemotherapy and radiation therapy.
Design: Participants will be screened with the following: Medical record review Medical history Physical exam Tests to assess their nervous system and their ability to do typical activities Blood tests Tumor assessment. For this, they will have magnetic resonance imaging (MRI). They may get a contrast dye through an intravenous (IV) catheter. The MRI scanner makes noise. They will get earplugs. Electrocardiogram. It measures heart rate and rhythm. They will lie still. Sticky pads will be placed on their chest, arms, and legs. Screening tests will be repeated during the study. Treatment will be given in cycles. Each cycle lasts 4 weeks. Participants will get nivolumab and ipilimumab via IV. They will take temozolomide by mouth. They will keep a pill diary. Participants will fill out surveys about their symptoms. Participants will have follow-up visits about 60 days and 100 days after treatment ends. Then they will be contacted every 6 months for the rest of their life.
⁃ Participants must have newly diagnosed histologically confirmed primary glioblastoma or gliosarcoma
⁃ Participants must have undergone an extensive resection of unifocal, confined to the supratentorial compartment, tumor.
⁃ Participant must have completed chemoradiation (external beam radiation with concurrent temozolomide) a maximum of 5 weeks prior to initiation of study therapy. Potential participants who have a limited short term, reversable, unrelated to their underlying disease, concurrent illness, the initiation of treatment may be delayed up to 14 days, if the participant meet all other I/E criteria at that time.
⁃ Age greater than or equal to 18 years.
⁃ Karnofsky greater than or equal to 70%
⁃ Participants must have adequate organ and marrow function as defined below:
∙ Absolute neutrophil count greater than or equal to 1,500/mcL
‣ Platelet Count \>100,000/mcL
‣ Hemoglobin \> 9.0 g/dL (may be transfused to achieve this level)
‣ BUN less than or equal to 30 mg/dL
‣ Serum creatinine less than or equal to 1.7 mg/dL or creatinine clearance as measured by 24 hour urine collection as \> 60 ml/min.
‣ Total bilirubin (except participants 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
‣ ALT and AST less than or equal to 2.5x institutional upper limit of normal.
⁃ The effects of study treatment on the developing human fetus are unknown. For this reason, participants of reproductive potential must agree to abstinence or use adequate contraception which includes a combination of TWO of the following:
∙ Barrier method of contraception: condoms (male or female) with or without a spermicidal agent, diaphragm, or cervical cap with spermicide
‣ IUD
‣ Hormone-based contraceptive
‣ Tubal ligation
• Note: Consider use in individuals of child-bearing potential (IOCBP) only or both individuals who can father children and IOCBP starting from the enrollment and for the duration of study treatment and up to 6 months (IOCBP) after the last dose of study drug and 6 months (if individual can father children) after the last dose of temozolomide. Should a IOCBP become pregnant or suspect pregnancy while the individual or partner is participating in this study, the individual should inform the treating physician immediately.
• The participant must be able to understand and be willing to sign a written informed consent document.