Pembrolizumab and Standard Therapy in Treating Patients With Glioblastoma
Glioblastoma, Gliosarcoma, Supratentorial Glioblastoma
About this trial
This is an interventional treatment trial for Glioblastoma
Eligibility Criteria
Inclusion Criteria:
- Histological confirmation of supratentorial glioblastoma (also known as astrocytoma grade IV, gliosarcoma)
Neoadjuvant patients only: Have an enhancing mass on magnetic resonance imaging (MRI) amenable to > 90% resection of contrast-enhancing tumor (as determined by the neurosurgeon pre-operatively) and histological diagnosis of glioblastoma from a prior biopsy or surgery
- NOTE: Biopsy or subtotal resection must have been =< 43 days prior to registration
- Neoadjuvant patients only: Willing to undergo craniotomy and resection of their glioblastoma at Mayo Clinic in Rochester, Minnesota (MN)
- Adjuvant patients only: Must have undergone craniotomy and resection of their glioblastoma =< 6 weeks prior to registration
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
- Absolute neutrophil count (ANC) >= 1500/mm^3 (obtained =< 28 days prior to registration)
- Platelet count >= 100,000/mm^3 (obtained =< 28 days prior to registration)
- Hemoglobin >= 9.0 g/dL without transfusion or erythropoietin (EPO) dependency (=< 7 days prior to assessment) (obtained =< 28 days prior to registration)
- Prothrombin time (PT) =< 1.5 x upper limit of normal (ULN) unless patient is receiving anticoagulant therapy and PT or partial prothrombin time (PTT) is within therapeutic range of intended use of coagulants (obtained =< 28 days prior to registration)
- Activated partial thromboplastin time (aPTT) =< 1.5 x ULN unless patient is receiving anticoagulant therapy and PT or PTT is within therapeutic range of intended use of coagulants (obtained =< 28 days prior to registration)
- Albumin >= 2.5 mg/dL (obtained =< 28 days prior to registration)
- Total bilirubin =< 1.5 x ULN OR direct bilirubin =< ULN for patients with total bilirubin levels > 1.5 x ULN (obtained =< 28 days prior to registration)
- Aspartate transaminase (AST) AND alanine transaminase (ALT) =< 2.5 x ULN (obtained =< 28 days prior to registration)
- Creatinine =< 1.0 x ULN OR measured or calculated creatinine clearance (per institutional standard) must be >= 60 ml/min (obtained =< 28 days prior to registration)
Negative pregnancy test done =< 7 days prior to registration, for persons of childbearing potential only (POCBP)
- NOTE: Serum or urine pregnancy test allowed; if urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
- POCBP must be willing to use adequate contraception starting with first dose through 120 days after last dose
- Provide written informed consent
Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)
- Note: During the active monitoring phase of a study (i.e., active treatment and observation), participants must be willing to return to the consenting institution for follow-up
- Willing to provide tissue and blood samples for correlative research purposes
Exclusion Criteria:
Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:
- Pregnant persons
- Nursing persons
- Persons of childbearing potential who are unwilling to employ adequate contraception
- Neoadjuvant patients only: Signs or symptoms of life-threatening raised intracranial pressure: as defined by the treating neurosurgeon, including severe headache, nausea, decreasing level of consciousness, precluding 4-7 day delay in scheduling neurosurgery
- Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
- Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
Other active malignancy =< 5 years prior to registration
- EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix
- NOTE: If there is a history or prior malignancy, the patient must not be receiving other specific treatment for their cancer
- History of myocardial infarction =< 6 months prior to registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
- Active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs; NOTE: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
- Known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
- Known history of active TB (Bacillus tuberculosis)
- Received a live vaccine =< 30 days prior to registration
- History of (non-infectious) pneumonitis that required steroids or current pneumonitis
- Hypersensitivity to pembrolizumab or any of its excipients
- Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
- Received or planning to receive Optune device
Sites / Locations
- Mayo Clinic Hospital in Arizona
- Mayo Clinic in Arizona
- Mayo Clinic in Rochester
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
Group 1 (pembrolizumab, surgery, temozolomide, radiation)
Group 2 (pembrolizumab, temozolomide, radiation therapy )
NEOADJUVANT (CYCLE 1): Patients receive pembrolizumab IV over 30 minutes on day 1. SURGERY (CYCLE 2): Patients undergo standard of care surgery within days 4-7. CONCURRENT (CYCLE 3): Starting 21-35 days after surgery, patients receive pembrolizumab IV over 30 minutes on days 1, 22, and 43 and temozolomide PO daily on days 8-54. Patients also undergo external beam radiation therapy every 5 days per week on days 8-54. ADJUVANT (CYCLE 4-8): Within 3-5 weeks after completing radiation therapy, patients receive pembrolizumab IV over 30 minutes on days 1, 22, and 43 and temozolomide PO daily on days 1-5 every 28 days. Treatment repeats every 63 days for up to 5 cycles in the absence of disease progression or unexpected toxicity.
CONCURRENT (CYCLE 1): Starting 21-35 days after surgery, patients receive pembrolizumab IV over 30 minutes on days 1, 22, and 43 and temozolomide PO daily on days 8-54. Patients also undergo external beam radiation therapy every 5 days per week on days 8-54. ADJUVANT (CYCLES 2-6): Within 3-5 weeks after completing radiation therapy, patients receive pembrolizumab IV over 30 minutes on days 1, 22, and 43 of cycles 2-5 and 1 and 22 of cycle 6 (up to a total of 17 doses). Patients also receive temozolomide PO daily on days 1-5, 29-33, and 57-61 of cycles 2 and 6, days 22-26 and 50-54 of cycle 3, days 15-19 and 43-47 of cycle 4, days 8-12 and 36-40 of cycle 5. Treatment repeats every 63 days for up to 5 cycles in the absence of disease progression or unexpected toxicity.