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

Phase 2RecruitingNCT04977375

Chirag G. Patil10 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Glioblastoma Multiforme

Interventions

Pembrolizumab

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: From start of study treatment until death, loss to follow-up, or withdrawal of consent. Assessed up to 2 years.

Secondary Outcomes

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.

Time frame: 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

Time frame: At baseline, prior to stereotactic radiation therapy, and prior to surgery.