| Eligibility |
Inclusion Criteria:
- Age >= 18 years
- Disease characteristics:
- Progressive or recurrent World Health Organization (WHO) Grade IV IDH wildtype
glioblastoma (including molecular glioblastoma and gliosarcoma)
- Previously treated with maximum feasible resection or biopsy, radiation, and
temozolomide
- Have an enhancing mass on magnetic resonance imaging (MRI) amenable to resection or
biopsy of the tumor (as determined by the neurosurgeon pre-operatively) and
histological diagnosis of glioblastoma from a prior biopsy or surgery
- Willing to undergo clinically indicated resection or biopsy of their glioblastoma at
Mayo Clinic in Rochester, Minnesota (MN).
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1 and
Karnofsky Performance Scale (KPS) >= 70 NOTE: PS must be assessed (again) within 7
days prior to first dose of study drug
- Hemoglobin >= 9.0 g/dL (obtained =< 15 days prior to registration) (without
transfusion or erythropoietin [EPO] dependency =< 7 days prior to assessment)
- Absolute neutrophil count (ANC) >= 1500/mm^3 (obtained =< 15 days prior to
registration)
- Platelet count >= 100,000/mm^3 (obtained =< 15 days prior to registration)
- Creatinine =< 1.5 x upper limits of normal (ULN) OR measured or calculated creatinine
clearance (per institutional standard) must be >= 45 ml/min (obtained =< 15 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 =< 15 days prior to registration)
- Aspartate transaminase (AST) AND alanine transaminase (ALT) =< 2.5 x ULN (obtained =<
15 days prior to registration)
- Prothrombin time (PT)/international normalized ratio (INR)/activated partial
thromboplastin time (aPTT) =< 1.5 x ULN OR if patient is receiving anticoagulant
therapy then INR or aPTT is within target range of therapy (obtained =< 15 days prior
to registration)
- Negative pregnancy test done =< 7 days prior to registration, for persons of
childbearing potential only (POCBP) Note: If testing done for eligibility is > 72
hours prior to first dose, then pregnancy testing must be repeated, and result must be
negative for patient to receive treatment.
- POCBP or able to father a child must be willing to use adequate contraception starting
with first dose through 180 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).
- Willing to provide tissue and blood samples for correlative research purposes
Exclusion Criteria:
- Any of the following because this study involves an investigational agent for which
genotoxic, mutagenic, and teratogenic effects on the developing fetus and newborn are
unknown:
- Pregnant persons
- Nursing persons
- Persons of childbearing potential or able to father a child who are unwilling to
employ adequate contraception
- Signs or symptoms of life-threatening raised intracranial pressure: as determined by
the treating neurosurgeon, including severe headache, nausea, decreasing level of
consciousness, precluding 4-7-day delay in scheduling neurosurgery (i.e., immediate
surgery is indicated, and patient cannot wait).
- Prior treatment
- Received bevacizumab (AVASTIN) =< 4 months prior to registration
- Note: Bevacizumab is allowed for symptom control during the adjuvant phase
of the study
- Received a live vaccine =< 30 days prior to registration.
- Requirement for dexamethasone dose of > 2mg/day =< 2 days prior to registration
- Failure to recover from any adverse events related to any of the following therapies
received prior to registration:
- Major surgery =< 28 days prior to registration
- Radiation therapy =< 14 days prior to registration
- 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
- Known history of human immunodeficiency virus (HIV) infection
- 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 (e.g., drug addiction) that would
limit compliance with study requirements
- Receiving any other investigational agent
- Other active malignancy requiring systemic treatment =< 1 year prior to registration
- 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 (i.e., with use of
disease modifying agents, corticosteroids, or immunosuppressive drugs) =< 2 years
prior to registration 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
- Concurrent known active Hepatitis B (i.e., known positive hepatitis B virus [HBV]
surface antigen [HBsAg] reactive) AND known active Hepatitis C (i.e., hepatitis C
virus [HCV] ribonucleic acid [RNA] [qualitative] detected by polymerase chain reaction
[PCR])
- Note: No testing for Hepatitis B and Hepatitis C is required unless mandated by
local health authority
- NOTE: Patients with known Hepatitis B OR Hepatitis C may be enrolled if they meet
the following criteria:
- Hepatitis B: Patients who are HBsAG positive are eligible if they have
received HBV antiviral therapy for at least 4 weeks and have undetectable
HBV viral load prior to randomization. Patients should remain on anti-viral
therapy throughout the treatment phase of the trial and should follow local
guidelines for HBV anti-viral therapy after completing study treatment
- Hepatitis C: Patients with history of Hepatitis C infection are eligible if
HCV viral load is undetectable at screening. Patients must have completed
curative anti-viral therapy at least 4 weeks prior to registration
- Known history of active TB (Bacillus Tuberculosis)
- History of (non-infectious) pneumonitis or interstitial lung disease that required
steroids, or current pneumonitis or interstitial lung disease
- Hypersensitivity to pembrolizumab or any of its excipients
- Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
- History of allogenic tissue/solid organ transplant
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