A Pilot Surgical Trial to Evaluate Early Immunologic Pharmacodynamic Parameters for the PD-1 Checkpoint Inhibitor, Pembrolizumab (MK-3475), in Patients with Surgically Accessible Recurrent / Progressive Glioblastoma
The goal of this clinical research study is to learn if pembrolizumab (MK-3475) can help to control glioblastoma that has returned after treatment. The safety of this drug will also be studied. Participants in this study will also be having surgery for the brain tumor as part of standard care.
Treatment Location: N/A
1. Primary Objectives To test the hypothesis that administration of pembrolizumab (MK-3475) will induce statistically significant increases in tumor infiltrating T lymphocyte (TIL) density in recurrent/progressive GBM patients compared to an untreated concurrent control versus the null hypothesis of no difference the treatment and control groups. (Group A vs. Group B) To evaluate safety of study drug in this patient population 2. Secondary Objective To estimate percent six-month progression free survival (PFS6) in this patient population using Response Assessment in Neuro-Oncology (RANO) criteria 3. Exploratory Objectives To evaluate the associations between exploratory biomarkers and clinical outcomes and adverse events these include: Estimate correlation of quantitative assessments of TIL density or clonality with clinical responses to pembrolizumab in recurrent glioblastoma patients. Estimate efficacy of pembrolizumab by PFS, second PFS and OS. (Groups A and B) as defined by RANO. Estimate efficacy of pembrolizumab by PFS6, PFS, second PFS and OS. (Groups A and B) as defined by iRANO. Explore effect of pembrolizumab on TIL proliferation (CD8+KI-67+ staining). Estimate difference in PD-1 and programmed cell death ligand-1 (PDL-1) IHC expression between Group A and B as well as between archived and study samples. Explore whether oligoclonal T cell populations within tumor tissue are similarly expanded in peripheral blood after pembrolizumab, the magnitude of which correlates with clinical responses. Explore if changes in specific MRI parameters correlate with tumor and peripheral blood immune responses. Correlate Changes of FDG-PET in Tumor with: a. TIL Density or Clonality. b. Clinical outcome. c. T cell measures in Peripheral blood. d. Clinical Toxicity Correlate changes in FDG-PET in Lymph Nodes with: a. TIL Density or Clonality. b. Clinical outcome. c. T cell measures in Peripheral blood. d. Clinical toxicity Correlate changes in FDG-PET in Tissue Organ: a. TIL Density or Clonality. b. Clinical outcome. c. T cell measures in Peripheral blood. d. Clinical toxicity.
IRB Review and Approval Date: 03/29/2017
Recruitment Status: Closed
Projected Accrual: N/A
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