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

Glioblastoma Multiforme Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04977375
• Other study ID #: IIT2019-13-Patil-NeoPD1SRS
• Secondary ID: R21CA256421
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: December 9, 2021
• Est. completion date: December 2026

Study information

• Verified date: May 2024
• Source: Cedars-Sinai Medical Center
• Contact: Clinical Trial Recruitment Navigator
• Phone: 3104232133
• Email: cancer.trial.info[@]cshs.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: December 2026
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Glioblastoma
• Glioblastoma Multiforme

Intervention

Drug:
• Pembrolizumab
Pembrolizumab 400mg administered intravenously on Day 1, and then beginning 6 weeks post-surgery, subjects will receive 400 mg pembrolizumab every 6 weeks

Radiation:
• Stereotactic Radiation Therapy
Standard of care stereotactic radiation of 24 grays over 3 days, administered beginning on Day 7

Procedure:
• Surgical Resection
Standard of care surgical resection of tumor on Day 10-28

Locations

Country	Name	City	State
United States	Cedars-Sinai Medical Center	Los Angeles	California

Sponsors (3)

Lead Sponsor	Collaborator
Chirag G. Patil	Merck Sharp & Dohme LLC, National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	From start of study treatment until confirmation of disease progression, intolerable toxicities, withdrawal of consent. Assessed up to 2 years.
Primary	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	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.
Secondary	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.