Ipilimumab and/or Nivolumab in Combination With Temozolomide in Treating Patients With Newly Diagnosed Glioblastoma or Gliosarcoma

Inclusion Criteria:

• Histopathologically proven diagnosis of glioblastoma or gliosarcoma prior toregistration by pathology report
• The tumor must be unifocal, confined to the supratentorial compartment and haveundergone a gross total or near gross total resection; this will increase thelikelihood that the patient will not require corticosteroids or developpseudoprogression
• The formalin-fixed, paraffin-embedded (FFPE) tumor tissue block must be available tobe sent for retrospective central pathology review after registration
• Patients must be registered within 35 days of completion of chemoradiation
• History/physical examination within 7 days prior to registration
• Patients must have undergone an evaluation by magnetic resonance imaging (MRI) within 35 days of completing radiation and must also be within 7 days prior to registration;MRI must NOT demonstrate tumor progression, but patients with imaging changesconsistent with pseudo-progression, stable neurologic function and not needingcorticosteroid treatment are eligible
• Karnofsky performance status >= 70 within 7 days prior to registration
• Absolute neutrophil count >= 1,500 cells/mm^3
• Platelet count >= 100,000 cells/mm^3
• Hemoglobin (Hgb) > 9 g/dL (can be achieved with transfusion)
• Blood urea nitrogen (BUN) =< 30 mg/dl
• Serum creatinine =< 1.7 mg/dl
• Total bilirubin (except patients with Gilbert's syndrome, who are eligible for thestudy but exempt from the total bilirubin eligibility criterion) =< 2.0 mg/dl
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x upperlimit of normal (ULN)
• The patient must have completed chemoradiation (all cohorts) within standards of careestablished by prior Radiation Therapy Oncology Group (RTOG)/Network RadiotherapyGroup (NRG) Oncology studies as follows:
• Radiation therapy
• Modality: either 3-dimensional (3D) or intensity-modulated radiation therapy (IMRT), or proton therapy is allowed
• Time to initiation: radiotherapy must be initiated within or equal to 42days after surgery
• Target volumes: target volume definition will be based uponpostoperative-enhanced MRI; preoperative imaging should be used forcorrelation and improved identification, as necessary
• Dose guidelines: the initial target volume will be treated to 46 Gray (Gy)in 23 fractions; after 46 Gy, the cone-down or boost volume will be treatedto a total of 60 Gy, with seven additional fractions of 2 Gy each (14 Gyboost dose)
• Temozolomide during concomitant radiation therapy
• Temozolomide must have been administered continuously from day 1 ofradiotherapy to the last day of radiation (+/- 3 days to take intoconsideration holidays) at a daily oral dose of 75 mg/m^2 for a maximum of 49 days (except missed doses due to toxicity)
• The patient must not be on a corticosteroid dose greater than physiologic replacementdosing defined as 30 mg of cortisone per day or its equivalent
• The patient must provide study-specific informed consent prior to study entry
• Echocardiogram (ECHO) cardiogram and cardiology consultation required within 7 daysprior to registration for patients with a history of congestive heart failure orcardiovascular disease or history of exposure to cardiotoxic agents who are notalready excluded

Exclusion Criteria:

• Definitive clinical or radiologic evidence of progressive disease
• Prior placement of Gliadel wafer or local brachytherapy
• Use of an immunotherapy such as a vaccine therapy, dendritic cell vaccine orintracavitary or convectional enhanced delivery of therapy
• Prior invasive malignancy (except non-melanomatous skin cancer) unless disease freefor a minimum of 3 years
• Unstable angina within the last 6 months prior to registration
• Transmural myocardial infarction within the last 6 months prior to registration
• Evidence of recent myocardial infarction or ischemia by the findings of S-T elevationsof >= 2 mm using the analysis of an electrocardiogram (EKG) performed within 7 daysprior to registration
• New York Heart Association grade II or greater congestive heart failure requiringhospitalization within 12 months prior to registration
• History of stroke, cerebral vascular accident (CVA) or transient ischemic attackwithin 6 months prior to registration
• Serious and inadequately controlled cardiac arrhythmia
• Significant vascular disease (e.g., aortic aneurysm, history of aortic dissection) orclinically significant peripheral vascular disease
• Evidence of bleeding diathesis or coagulopathy
• Serious or non-healing wound, ulcer, or bone fracture or history of abdominal fistula,gastrointestinal perforation, intra-abdominal abscess major surgical procedure, openbiopsy, or significant traumatic injury within 28 days prior to registration, with theexception of the craniotomy for tumor resection
• Acute bacterial or fungal infection requiring intravenous antibiotics at the time ofregistration
• Chronic obstructive pulmonary disease exacerbation or other respiratory illnessrequiring hospitalization or precluding study therapy at the time of registration
• Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note,however, that laboratory tests for additional liver function tests and coagulationparameters are not required for entry into this protocol
• Acquired immune deficiency syndrome (AIDS) based upon current Centers for DiseaseControl and Prevention (CDC) definition; note, however, that human immunodeficiencyvirus (HIV) testing is not required for entry into this protocol
• Active connective tissue disorders, such as lupus or scleroderma, which in the opinionof the treating physician may put the patient at high risk for immunologic toxicity
• Patients with active autoimmune disease or history of autoimmune disease that mightrecur, which may affect vital organ function or require immune suppressive treatmentincluding systemic corticosteroids, should be excluded; these include but are notlimited to patients with a history of immune related neurologic disease, multiplesclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome or chronicinflammatory demyelinating polyneuropathy (CIDP), myasthenia gravis; systemicautoimmune disease such as systemic lupus erythematosus (SLE), connective tissuediseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis,hepatitis; and patients with a history of toxic epidermal necrolysis (TEN),Stevens-Johnson syndrome, or phospholipid syndrome should be excluded
• Of note, patients with vitiligo, endocrine deficiencies including thyroiditismanaged with replacement hormones including physiologic corticosteroids areeligible; patients with rheumatoid arthritis and other arthropathies, Sjogren'ssyndrome and psoriasis controlled with topical medication and patients withpositive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodiesshould be evaluated for the presence of target organ involvement and potentialneed for systemic treatment but should otherwise be eligible
• Any other major medical illnesses or psychiatric impairments that in theinvestigator's opinion will prevent administration or completion of protocol therapy
• Pregnancy or lactating females; women of childbearing potential must have a negativeserum pregnancy test within 7 days prior to registration
• History of severe hypersensitivity reaction to any monoclonal antibody