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

Primary Purpose

Glioblastoma Multiforme

Status

Recruiting

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Pembrolizumab

Stereotactic Radiation Therapy

Surgical Resection

About this trial

This is an interventional treatment trial for Glioblastoma Multiforme focused on measuring Central Nervous System Tumor, neurosurgery, Brain tumor, spinal cord tumor, surgical resection, glioma, glioblastoma, neuropathology, maximal safe resection, CNS

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Cedars-Sinai Medical CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Pembrolizumab with stereotactic radiation therapy and surgical resection

Arm Description

Outcomes

Primary Outcome Measures

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.

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.

Secondary Outcome Measures

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.

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

Full Information

NCT ID

NCT04977375

First Posted

April 22, 2021

Last Updated

January 19, 2023

Sponsor

Chirag G. Patil

Collaborators

Merck Sharp & Dohme LLC, National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT04977375

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2023

Overall Recruitment Status

Recruiting

Study Start Date

December 9, 2021 (Actual)

Primary Completion Date

December 2023 (Anticipated)

Study Completion Date

December 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Chirag G. Patil

Collaborators

Merck Sharp & Dohme LLC, National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. 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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Glioblastoma Multiforme

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Pembrolizumab with stereotactic radiation therapy and surgical resection

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

Pembrolizumab

Intervention Description

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

Intervention Type

Radiation

Intervention Name(s)

Stereotactic Radiation Therapy

Intervention Description

Standard of care stereotactic radiation of 24 grays over 3 days, administered beginning on Day 7

Intervention Type

Procedure

Intervention Name(s)

Surgical Resection

Intervention Description

Standard of care surgical resection of tumor on Day 10-28

Primary Outcome Measure Information:

Title

Safety and tolerability measured by the incidence of adverse events, serious adverse events and grade 3 or above treatment related adverse events.

Description

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.

Title

Overall survival

Description

Time Frame

From start of study treatment until death, loss to follow-up, or withdrawal of consent. Assessed up to 2 years.

Secondary Outcome Measure Information:

Title

Progression free survival

Description

Time Frame

From start of study treatment until until confirmation of disease progression, intolerable toxicities, withdrawal of consent. Assessed up to 2 years.

Title

Immune action

Description

Time Frame

At baseline, prior to stereotactic radiation therapy, and prior to surgery.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Clinical Trial Recruitment Navigator

Phone

3104232133

cancer.trial.info@cshs.org

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Chirag G Patil, MD, MS

Organizational Affiliation

Cedars-Sinai Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Cedars-Sinai Medical Center

City

Los Angeles

State/Province

California

ZIP/Postal Code

90048

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Clinical Trial Recruitment Navigator

Phone

310-423-2133

cancer.trial.info@cshs.org

First Name & Middle Initial & Last Name & Degree

Stephen Shiao, MD, PhD

First Name & Middle Initial & Last Name & Degree

Jethro Hu, MD

First Name & Middle Initial & Last Name & Degree

Jeremy Rudnick, MD

First Name & Middle Initial & Last Name & Degree

Keith Black, MD

First Name & Middle Initial & Last Name & Degree

Ray Chu, MD

First Name & Middle Initial & Last Name & Degree

John Yu, MD

First Name & Middle Initial & Last Name & Degree

Adam Mamelak, MD

First Name & Middle Initial & Last Name & Degree

Amin Mirhadi, MD

First Name & Middle Initial & Last Name & Degree

Behrooz Hakimian, MD

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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