Pembrolizumab in Treating Patients With Recurrent Glioblastoma
Condition: Recurrent Glioblastoma; Recurrent Gliosarcoma
MeSH terms: Glioblastoma; Gliosarcoma; Recurrence
Intervention: Laboratory Biomarker Analysis; Pembrolizumab; Pharmacological Study; Therapeutic Conventional Surgery
Intervention description: Correlative studies; Given IV; Correlative studies; Undergo surgery
Intervention MeSH terms: Pembrolizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 18.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies the effects of pembrolizumab on the body, or pharmacodynamics, in
      patients with glioblastoma that has come back. Immunotherapy with monoclonal antibodies, such
      as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with
      the ability of tumor cells to grow and spread.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Be willing and able to provide written informed consent/assent for the trial

          -  Have histologically confirmed World Health Organization grade IV malignant glioma
             (glioblastoma or gliosarcoma); participants will be eligible if the original histology
             was low-grade glioma and a subsequent histological diagnosis of glioblastoma or
             variants is made

          -  Patients must be at first or second relapse and clinically require reoperation for
             tumor progression within 4 to 6 weeks; Note: relapse is defined as progression
             following initial therapy (i.e., radiation, chemotherapy, or radiation +
             chemotherapy); if the participant had a surgical resection for relapsed disease and no
             anti-tumor therapy instituted for up to 12 weeks, this is considered one relapse; for
             participants who had prior therapy for a low grade glioma, the surgical diagnosis of a
             high grade glioma will be considered first relapse

          -  Have measurable disease consisting of a minimal volume of 1 cm^3

          -  Have provided tissue from an archival tissue sample or newly obtained core or
             excisional biopsy of a tumor lesion

          -  Have a performance status of >= 60 on the Karnofsky performance scale (KPS)

          -  Stable dose of steroids for 5 days, no more than 2 mg dexamethasone (or equivalent)
             total per day

          -  Absolute neutrophil count (ANC) >= 1,500/mcL (performed within 14 days prior to
             registration)

          -  Platelets >=100,000/mcL (performed within 14 days prior to registration)

          -  Hemoglobin >= 9 g/dL or >= 5.6 mmol/L (performed within 14 days prior to registration)

          -  Serum creatinine =< 1.5 X upper limit of normal (ULN) OR measured or calculated
             creatinine clearance (glomerular filtration rate [GFR] can also be used in place of
             creatinine or creatinine clearance [CrCl]) >= 60 mL/min for subject with creatinine
             levels > 1.5 X institutional ULN (performed within 14 days prior to registration)

          -  Serum total bilirubin =< 1.5 X ULN OR direct bilirubin =< ULN for subjects with total
             bilirubin levels > 1.5 ULN (performed within 14 days prior to registration)

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and
             alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X
             ULN OR =< 5 X ULN for subjects with liver metastases (performed within 14 days prior
             to registration)

          -  International normalized ratio (INR) or prothrombin time (PT) =< 1.5 X ULN unless
             subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic
             range of intended use of anticoagulants (performed within 14 days prior to
             registration)

          -  Activated partial thromboplastin time (aPTT) =< 1.5 X ULN unless subject is receiving
             anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use
             of anticoagulants (performed within 14 days prior to registration)

          -  Female subject of childbearing potential should have a negative serum pregnancy test

          -  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; subjects of
             childbearing potential are those who have not been surgically sterilized or have not
             been free from menses for > 1 year

          -  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

        Exclusion Criteria:

          -  Has been treated previously with bevacizumab

          -  Has tumor localized primarily to the brainstem or spinal cord

          -  Has received prior interstitial brachytherapy, implanted chemotherapy, or therapeutics
             delivered by local injection or convection enhanced delivery

          -  Is currently participating in or has participated in a study of an investigational
             agent or using an investigational device 4 weeks since last dose of agent
             administration

          -  Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy > 2 mg of
             dexamethasone total per day or any other form of immunosuppressive therapy within 7
             days prior to the first dose of trial treatment

          -  Has had a prior monoclonal antibody within 4 weeks prior to study day 1 or who has not
             recovered (i.e., =< grade 1 or at baseline) from adverse events due to agents
             administered more than 4 weeks earlier

          -  Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy
             within 2 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at
             baseline) from adverse events due to a previously administered agent; Note: subjects
             with alopecia, =< grade 2 neuropathy are an exception to this criterion and may
             qualify for the study

          -  Has a known additional malignancy that is progressing or requires active treatment;
             exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the
             skin, or in situ cervical cancer that has undergone potentially curative therapy

          -  Has known carcinomatous meningitis, extracranial disease, or multifocal disease

          -  Has an active autoimmune disease requiring systemic treatment within the past 3 months
             or a documented history of clinically severe autoimmune disease, or a syndrome that
             requires systemic steroids or immunosuppressive agents; subjects with vitiligo or
             resolved childhood asthma/atopy would be an exception to this rule; subjects that
             require intermittent use of bronchodilators or local steroid injections would not be
             excluded from the study; subjects with hypothyroidism stable on hormone replacement or
             Sjogren's syndrome will not be excluded from the study

          -  Has evidence of interstitial lung disease or active, non-infectious pneumonitis

          -  Has an active infection requiring systemic therapy

          -  Has a history or current evidence of any condition, therapy, or laboratory abnormality
             that might confound the results of the trial, interfere with the subject's
             participation for the full duration of the trial, or is not in the best interest of
             the subject to participate, in the opinion of the treating investigator

          -  Has known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the trial

          -  Is pregnant or breastfeeding, or expecting to conceive or father children within the
             projected duration of the trial, starting with the screening visit through 120 days
             after the last dose of trial treatment

          -  Has received prior therapy with an anti-programmed cell death (PD)-1, anti-PD ligand
             (PD-L)1, anti-PD-L2, anti-cluster of differentiation (CD)137 antibody (including
             ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation
             or checkpoint pathways)

          -  Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies);
             testing not required

          -  Has known history of 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); testing not required

          -  Has received a live vaccine within 30 days prior to the first dose of trial treatment