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

• ClinicalTrials.gov Identifier: NCT04977375
• Recruitment Status: Recruiting
• First Posted: July 26, 2021
• Last Update Posted: January 20, 2023
• Sponsor: Chirag G. Patil
• Collaborators: Merck Sharp & Dohme LLC; National Cancer Institute (NCI)
• Information provided by (Responsible Party): Chirag G. Patil, Cedars-Sinai Medical Center

Study Description

Brief 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

Condition or disease	Intervention/treatment	Phase
Glioblastoma Multiforme	Drug: Pembrolizumab; Radiation: Stereotactic Radiation Therapy; Procedure: Surgical Resection	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase Ib/II Trial of Anti-PD-1 Immunotherapy and Stereotactic Radiation in Patients With Recurrent Glioblastoma
• Actual Study Start Date: December 9, 2021
• Estimated Primary Completion Date: December 2023
• Estimated Study Completion Date: December 2024

Arms and Interventions

Arm

Intervention/treatment

Experimental: Pembrolizumab with stereotactic radiation therapy and surgical resection

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

Outcome Measures

Primary Outcome Measures :

1. Safety and tolerability measured by the incidence of adverse events, serious adverse events and grade 3 or above treatment related adverse events. [ Time Frame: From start of study treatment until confirmation of disease progression, intolerable toxicities, withdrawal of consent. Assessed up to 2 years. ]
   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.
2. Overall survival [ Time Frame: From start of study treatment until death, loss to follow-up, or withdrawal of consent. Assessed up to 2 years. ]
   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.

Secondary Outcome Measures :

1. 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. ]
   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.
2. Immune action [ Time Frame: At baseline, prior to stereotactic radiation therapy, and prior to surgery. ]
   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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Contacts

Contact: Clinical Trial Recruitment Navigator; 3104232133; cancer.trial.info@cshs.org

Locations

United States, California

Cedars-Sinai Medical Center; Recruiting

Los Angeles, California, United States, 90048

Contact: Clinical Trial Recruitment Navigator 310-423-2133 cancer.trial.info@cshs.org

Principal Investigator: Stephen Shiao, MD, PhD

Sub-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

Sponsors and Collaborators

Chirag G. Patil

Merck Sharp & Dohme LLC

National Cancer Institute (NCI)

Investigators

• Principal Investigator: Chirag G Patil, MD, MS; Cedars-Sinai Medical Center

  Study Documents (Full-Text)

Documents provided by Chirag G. Patil, Cedars-Sinai Medical Center:

Informed Consent Form  [PDF] October 4, 2022

More Information

• Responsible Party: Chirag G. Patil, Associate Professor of Neurosurgery Program Director, Neurosurgery Residency Training, Cedars-Sinai Medical Center
• ClinicalTrials.gov Identifier: NCT04977375
• Other Study ID Numbers: IIT2019-13-Patil-NeoPD1SRS; R21CA256421 ( U.S. NIH Grant/Contract )
• First Posted: July 26, 2021
• Last Update Posted: January 20, 2023
• Last Verified: January 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Chirag G. Patil, Cedars-Sinai Medical Center:

Central Nervous System Tumor; neurosurgery; Brain tumor; spinal cord tumor; surgical resection; glioma; glioblastoma; neuropathology; maximal safe resection; CNS

Additional relevant MeSH terms:

Glioblastoma; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Pembrolizumab; Antineoplastic Agents, Immunological; Antineoplastic Agents