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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04977375
Recruitment Status : Not yet recruiting
First Posted : July 26, 2021
Last Update Posted : July 26, 2021
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Chirag G. Patil, Cedars-Sinai Medical Center

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

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Study Type : Interventional  (Clinical Trial)
Estimated 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
Estimated Study Start Date : July 2021
Estimated Primary Completion Date : July 2023
Estimated Study Completion Date : July 2024

Resource links provided by the National Library of Medicine


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




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



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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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04977375


Contacts
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Contact: Karen Kearns 3109670692 Karen.Kearns@cshs.org

Locations
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United States, California
Cedars-Sinai Medical Center
Los Angeles, California, United States, 90048
Contact: Karen Kearns    310-967-0692    Karen.Kearns@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 Corp.
Investigators
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Principal Investigator: Chirag G Patil, MD, MS Cedars-Sinai Medical Center
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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: July 26, 2021    Key Record Dates
Last Update Posted: July 26, 2021
Last Verified: July 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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