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

• Sponsor: Chirag G. Patil (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT04977375
• Collaborator: Merck Sharp & Dohme LLC (Industry)
• Enrollment: 30
• Location: 1
• Arm: 1
• Anticipated Duration (Months): 35.7
• Patients Per Site Per Month: 0.8

Study Details

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
• Anticipated Enrollment: 30 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: Dec 9, 2021
• Anticipated Primary Completion Date: Dec 1, 2023
• Anticipated Study Completion Date: Dec 1, 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. [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 [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 [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 [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

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cedars-Sinai Medical Center	Los Angeles	California	United States	90048

Sponsors and Collaborators

• Chirag G. Patil
• Merck Sharp & Dohme LLC

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• 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
• First Posted: Jul 26, 2021
• Last Update Posted: Mar 11, 2022
• Last Verified: Feb 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• 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, Associate Professor of Neurosurgery Program Director, Neurosurgery Residency Training, 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; Pembrolizumab

Study Results

No Results Posted as of Mar 11, 2022