Neoadjuvant Chemoimmunotherapy in Recurrent Glioblastoma

Eligibility Criteria

• 1. Histopathologically proven diagnosis of glioblastoma prior to registration, by pathology report;
• 2. The tumor must be confined to the supratentorial compartment
• 3. The tumor tissue block from the primary diagnosis must be available to be sent for pathology review, after registration.
• 4. History/physical examination within 7 days prior to registration
• 5. Karnofsky performance status ≥ 60 within 7 days prior to registration.
• 6. Adequate Organ Function Laboratory Values
• * Absolute neutrophil count (ANC) ≥1,500/mcL
• * Platelets ≥100,000/mcL
• * Hemoglobin ≥9.0 g/gL or ≥5.6 mmol/L, without recent transfusion
• * Creatine ≤1.7 x upper limit of normal (ULN) or Measure or Calculated creatinine clearance ≥ 60.0mL/min for subject with creatinine levels \> 1.5 X institutional ULN (GFR can also be used in place of creatinine or CrCl)
• * Total bilirubin ≤ 1.5 x ULN or Direct bilirubin ≤ ULN for subjects with total bilirubin levels \> 1.5 x ULN
• * AST (SGOT) and ALT (SGPT) ≤ 2.5 x ULN or ≤ 5 x ULN for subjects with liver metastases
• 7. The patient must have completed chemoradiation with Radiotherapy and Temozolomide of the primary tumor according to standard of care.
• 8. Patients must have received no more than 3 prior therapies for Recurrent High Grade Glioma.
• 9. Subjects must have the ability to understand and willingness to sign a written informed consent document.
• 10. Female subjects of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• 11. Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication.
• 12. Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.
• 1. Previous use of an immunotherapy such as a vaccine therapy, dendritic cell vaccine or intracavitary or convectional enhanced delivery of therapy.
• 2. Prior invasive malignancy (except non-melanomatous skin cancer) within the previous three years
• 3. Severe, active co-morbidity defined as follows:
• * Transmural myocardial infarction or unstable angina within the last 6 months prior to registration
• * History of stroke, cerebral vascular accident (CVA) or transient ischemic attack within 6 months prior to registration
• * Significant vascular disease (e.g., aortic aneurysm, history of aortic dissection) or clinically significant peripheral vascular disease
• * Known history of Tuberculosis or acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
• * Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration
• * Patients with active autoimmune disease or history of autoimmune disease that might recur, will be considered on an individual basis
• * Any other major medical illnesses or psychiatric impairments that in the investigator's opinion will prevent administration or completion of protocol therapy.
• * Is pregnant or breastfeeding
• * Has received prior therapy with an anti-Programmed Death 1 (PD-1), anti- Programmed Death-ligand 1 (PD-L1), or anti- Programmed Death-ligand 1 (PD-L2) agent.
• 4. Patient must have \< 1.5 cm midline shift pre-operative
• 5. History of severe hypersensitivity reaction to any monoclonal antibody including pembrolizumab.
• 6. Patients who cannot safely undergo MRI due to non-MRI compatible pacemaker, or other reason.