RecruitingInterventionalPhase 1/Phase 2

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

NCT ID: NCT04977375Sponsor: Chirag G. PatilLast updated: 2025-09-03

Summary

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

Arms & interventions

DrugPembrolizumab
Pembrolizumab 400mg administered intravenously on Day 1, and then beginning 6 weeks post-surgery, subjects will receive 400 mg pembrolizumab every 6 weeks
RadiationStereotactic Radiation Therapy
Standard of care stereotactic radiation of 24 grays over 3 days, administered beginning on Day 7
ProcedureSurgical Resection
Standard of care surgical resection of tumor on Day 10-28

Outcome measures

Primary

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

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

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No

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.

Study locations (1)

Cedars-Sinai Medical Center

Los Angeles, California, 90048

Recruiting

Clinical Trial Recruitment Navigator · Contact

310-423-2133 cancer.trial.info@cshs.org

Stephen Shiao, MD, PhD · Principal Investigator

Jethro Hu, MD · Sub Investigator

Jeremy Rudnick, MD · Sub Investigator

Keith Black, MD · Sub Investigator

Ray Chu, MD · Sub Investigator

John Yu, MD · Sub Investigator

Adam Mamelak, MD · Sub Investigator

Amin Mirhadi, MD · Sub Investigator

Behrooz Hakimian, MD · Sub Investigator