Atezolizumab and Pre-Surgical Brain Radiation Therapy for Glioblastoma Multiforme

A Pilot Study to Evaluate the Immunogenic Effects of Window-of-Opportunity Fractionated Stereotactic Radiotherapy Combined With Atezolizumab for Patients With Newly Diagnosed WHO CNS Grade 4 Glioma (Glioblastoma Multiforme)

This is a single-arm pilot study that will recruit 12 patients with newly diagnosed Glioblastoma, a malignant brain tumor with a poor prognosis. Patients will be treated with fractionated stereotactic radiotherapy (FSRT) for 2 weeks, in addition to two doses of Atezolizumab (Tecentriq), an FDA approved PD- L1 inhibitor drug, 840 mg IV, at the beginning and at the end of the two-week time period, concomitantly with FSRT. After this initial two weeks treatment the patients will undergo craniotomy and maximal safe resection as per normal care for a GB. After surgery patients will follow the normal care for glioblastoma in addition to Atezolizumab 840 mg IV q2 weeks for the duration of adjuvant treatment.

Study Overview

• Status: Recruiting
• Conditions: Glioblastoma Multiforme
• Intervention / Treatment: Combination product: Atezolizumab + FSRT radiation

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Alexander Stessin, MD; Phone Number: 631-638-1000; Email: alexander.stessin@stonybrookmedicine.edu
• Study Contact Backup: Name: Catherine Izzo, MS; Phone Number: 631-372-7212; Email: catherine.izzo@stonybrookmedicine.edu

Study Locations

• United States
  • New York
    • Stony Brook, New York, United States, 11794
      • Recruiting
      • Stony Brook University Hospital
      • Contact: Caterina Vacchi-Suzzi, PhD; Phone Number: 631-216-2993; Email: caterina.vacchi-suzzi@stonybrookmedicine.edu
      • Contact: Alexander M Stessin, MD; Phone Number: 631-444-2200; Email: alexander.stessin@stonybrookmedicine.edu

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Diagnosis of glioblastoma multiforme WHO Grade IV
• The patient is a surgical candidate, with the surgical intent for a > 80% resection of the lesion
• Negative pregnancy test
• ECOG status <= 2
• Tumor volume <= 3.5 cm
• Adequate organ function
• Negative for infectious disease (human immunodeficiency virus, Hepatitis B Virus, Hepatitis C Virus, tubercolosis)

Exclusion Criteria:

• Presence of leptomeningeal disease, gliomatosis cerebri, multifocal disease, bilateral cerebral hemisphere involvement ("butterfly" gliomas)
• Patients at increased risk of neurologic decompensation
• Continued use of high dose intravenous or oral corticosteroids, or > 8milligrams per day of systemic dexamethasone
• Uncontrolled tumor-related pain
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
• Uncontrolled or symptomatic hypercalcemia
• History of autoimmune disease or immune deficiency
• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis
• Significant cardiovascular disease
• History of other malignancy within 1 year prior to screening
• Severe infection within 4 weeks prior to initiation of study treatment
• History of allogeneic stem cell or organ transplant
• Prior treatment with CD137 agonists or immune checkpoint blockade therapies
• Treatment with systemic immunostimulatory agents
• Treatment with systemic immunosuppressive medication

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment	Combination product: Atezolizumab + FSRT radiation; Atezolizumab 840mg IV every 2 weeks Fractionated Stereotactic Radiotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants who progress/relapse after surgical resection	Assess the efficacy of atezolizumab in combination with fractionated stereotactic radiation therapy in the neoadjuvant setting for resectable glioblastoma multiforme	2 years
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0	Assess the safety of atezolizumab in combination with fractionated stereotactic radiation therapy in the neoadjuvant setting for resectable glioblastoma multiforme	30 days after the last dose of atezolizumab

Collaborators and Investigators

• Sponsor: Stony Brook University
• Collaborators: Genentech, Inc.
• Investigators: Principal Investigator: Alexander Stessin, MD, Stony Brook Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): October 25, 2022
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: June 14, 2022
• First Submitted That Met QC Criteria: June 14, 2022
• First Posted (Actual): June 21, 2022

Study Record Updates

• Last Update Posted (Actual): February 26, 2024
• Last Update Submitted That Met QC Criteria: February 22, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Atezolizumab
• Other Study ID Numbers: SBU-FSRT-NEURO

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No