Trial of Anti-PD-1 Immunotherapy and Stereotactic Radiation in Patients With Recurrent Glioblastoma

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety/tolerability/feasibility of pembrolizumab and radiation therapy before surgical resection in patients with recurrent glioblastoma as defined by treatment-related AEs and the number of patients who do not necessitate a delay in surgical resection, and to assess overall survival. The secondary objectives are to assess progression free survival, and to assess the T cell clonality, CD8 T cell activation and Tumor Infiltrating Lymphocyte (TIL) score after treatment

Official Title
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Phase Ib/II Trial of Anti-PD-1 Immunotherapy and Stereotactic Radiation in Patients With Recurrent Glioblastoma

Conditions
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Glioblastoma Multiforme

Intervention / Treatment
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* Drug: Pembrolizumab
* Radiation: Stereotactic Radiation Therapy
* Procedure: Surgical Resection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 years or older Confirmed histologic diagnosis of WHO Grade IV, Glioblastoma Multiforme GBM recurrence or progression with planned standard of care surgical resection and repeat radiation Tumor size less than 6 cm ECOG performance status of 0-1 Adequate laboratory values Exclusion Criteria: Contraindication to additional radiation Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor Immunodeficiency diagnosis or receiving chronic systemic steroid therapy (exceeding 10 mg daily of prednisone) or any other form of immunosuppressive therapy Severe hypersensitivity to pembrolizumab Complete inclusion/exclusion criteria are detailed in the protocol.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pembrolizumab with stereotactic radiation therapy and surgical resection<br> | Drug: Pembrolizumab<br>* Pembrolizumab 400mg administered intravenously on Day 1, and then beginning 6 weeks post-surgery, subjects will receive 400 mg pembrolizumab every 6 weeks<br>Radiation: Stereotactic Radiation Therapy<br>* Standard of care stereotactic radiation of 24 grays over 3 days, administered beginning on Day 7<br>Procedure: Surgical Resection<br>* Standard of care surgical resection of tumor on Day 10-28<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability measured by the incidence of adverse events, serious adverse events and grade 3 or above treatment related adverse events. | Safety and tolerability measured by the incidence of adverse events, serious adverse events and grade 3 or above treatment related adverse events as assessed per CTCAE, Version 5.0. | From start of study treatment until confirmation of disease progression, intolerable toxicities, withdrawal of consent. Assessed up to 2 years. | 
| Overall survival | From start of study treatment until death, loss to follow-up, or withdrawal of consent. Subjects who are lost to survival follow-up will not be replaced, and public records may be accessed to assess Overall Survival. | From start of study treatment until death, loss to follow-up, or withdrawal of consent. Assessed up to 2 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival | From start of study treatment until confirmation of disease progression (per iRANO Criteria), intolerable toxicities, withdrawal of consent, or up to 2 years or 18 cycles of pembrolizumab, whichever comes first. | From start of study treatment until until confirmation of disease progression, intolerable toxicities, withdrawal of consent. Assessed up to 2 years. | 
| Immune action | To assess the T cell clonality, CD8 T cell activation and Tumor Infiltrating Lymphocyte (TIL) score after treatment. Blood draws for research purposes performed after obtaining consent but prior to neoadjuvant pembrolizumab administration, and at the time of initiation of SRT and at the time of surgery | At baseline, prior to stereotactic radiation therapy, and prior to surgery. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Central Nervous System Tumor, neurosurgery, Brain tumor, spinal cord tumor, surgical resection, glioma, glioblastoma, neuropathology, maximal safe resection, CNS