Avelumab with or without Laser Interstitial Thermal Therapy in Treating Patients with Recurrent Glioblastoma

Inclusion Criteria

• Patients must have histologically proven GBM from the initial resection
• First recurrence except for patients who are re-challenged with temozolomide
• Patients must have a life expectancy > 16 weeks. Patients must have a Karnofsky performance status of >= 60 or Eastern Cooperative Oncology Group (ECOG) 0 – 2
• Patient’s requirement for dexamethasone should be =< 4 mg daily or a stable dose at enrollment
• White blood cell count (WBC) > 3,000/ul (performed within 14 days prior to study day 1)
• Absolute neutrophil count (ANC) > 1,500/mm^3 (performed within 14 days prior to study day 1)
• Platelet count of > 100,000/mm^3 (performed within 14 days prior to study day 1)
• Hemoglobin > 9 gm/dl (performed within 14 days prior to study day 1)
• Total bilirubin level =< 1.5 x the upper limit of normal (ULN) range
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels =< 2.5 x ULN for all subjects
• Estimated creatinine clearance >= 30 mL/min according to the Cockcroft-Gault formula (or local institutional standard method)
• Highly effective contraception for both male and female subjects if the risk of conception exists. (Note: The effects of the trial drug on the developing human fetus are unknown; thus, women of childbearing potential and men able to father a child must agree to use two highly effective contraception, defined as methods with a failure rate of less than 1 % per year. Highly effective contraception is required at least 28 days prior, throughout and for at least 60 days after avelumab treatment
• All patients must sign an informed consent approved by the Institutional Review Board indicating that they are aware of the investigational nature of this study. Patients must also sign an authorization for the release of their protected health information

Exclusion Criteria

• Known history of autoimmune disorder except diabetes mellitus type 1, vitiligo or hypothyroidism only requiring hormone replacement
• Patients who have received any other therapeutic investigational agent within 30 days of enrollment with the exception of the personalized mutation-derived tumor antigen (MTA) vaccine (NCT03223103) that can be continued throughout the study
• Prior placement of intracavitary Gliadel wafers, as this treatment can result in an inflammatory reaction that mimics disease progression on MRI
• Prior treatment with PD-1/PD-L1 checkpoint inhibitors
• Presence of any other active malignancy, except for: basal cell carcinoma of the skin, cervical carcinoma in situ, early stage prostate carcinoma not requiring active treatment
• Patients with clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (>= New York Heart Association Classification class II), or serious cardiac arrhythmia requiring medication
• Prior organ transplantation, including allogeneic stem cell transplantation
• Significant acute or chronic infections including, among others: * Known history of testing positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) * Positive test for hepatitis B virus (HBV) surface antigen and / or confirmatory hepatitis C virus (HCV) ribonucleic acid (RNA) (if anti-HCV antibody tested positive) * Active infection requiring systemic therapy
• Known severe hypersensitivity reactions to monoclonal antibodies (grade >= 3 National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE)] version [v] 4.03), any history of anaphylaxis, or uncontrolled asthma (that is, 3 or more features of partially controlled asthma)
• Persisting toxicity related to prior therapy of grade > 1 NCI CTCAE v. 4.03; however, alopecia and sensory neuropathy grade =< 2 is acceptable
• Pregnancy or lactation
• Known alcohol or drug abuse
• All other significant diseases (for example, inflammatory bowel disease, which, in the opinion of the investigator, might impair the subject’s tolerance of trial treatment
• Any psychiatric condition that would prohibit the understanding or rendering of informed consent
• Vaccination within 4 weeks of the first dose of avelumab is prohibited except for administration of MTA vaccine (NCT03223103)
• Other: patients with other severe acute or chronic medical conditions including immune colitis, inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study