What is the mechanism of action of this treatment?

Tocilizumab, an IL-6 receptor antagonist, reduces inflammation and immune suppression around the tumor, potentially enhancing the effectiveness of other treatments. Atezolizumab, a PD-L1 inhibitor, blocks the interaction between PD-L1 on tumor cells and PD-1 on T-cells, boosting the immune system's ability to attack the tumor. Fractionated Stereotactic Radiation Therapy delivers precise, high-dose radiation to the tumor, minimizing damage to surrounding healthy tissue. These mechanisms are vital for Glioblastoma patients as they aim to improve immune response effectiveness and reduce tumor growth while minimizing side effects.

What side effects are associated with this type of intervention?

Tocilizumab, an IL-6 receptor antagonist, can cause infections, elevated liver enzymes, and gastrointestinal perforations. Atezolizumab, a PD-L1 inhibitor, is associated with immune-related adverse events such as colitis, pneumonitis, hepatitis, endocrinopathies, and skin reactions. Fractionated Stereotactic Radiation Therapy can lead to fatigue, skin changes, and potential long-term effects like cognitive decline and radiation necrosis. Combining these therapies may increase the risk of overlapping toxicities, requiring careful monitoring.

What prior FDA approvals exist?

The FDA has approved several treatments for Glioblastoma, including temozolomide, an oral alkylating agent, and bevacizumab, an anti-VEGF monoclonal antibody. While specific approvals for IL-6 receptor antagonists like Tocilizumab and PD-L1 inhibitors like Atezolizumab in Glioblastoma are not detailed, these types of immunotherapies are being actively studied. Fractionated Stereotactic Radiation Therapy, a precise radiation delivery method, is commonly used in Glioblastoma treatment to target tumors while minimizing damage to surrounding tissue. These therapies aim to improve outcomes by enhancing the immune response and delivering targeted radiation.

What other types of research exist?

Promising novel alternatives for Glioblastoma treatment in 2024 include: 1) CAR-T cell therapy targeting specific tumor antigens, 2) Oncolytic virus therapy such as Toca 511, which selectively infects and kills tumor cells, 3) Tumor Treating Fields (TTF) which uses electric fields to disrupt cancer cell division, and 4) New checkpoint inhibitors like Nivolumab (PD-1 inhibitor) combined with other agents such as Ipilimumab (CTLA-4 inhibitor).

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Monoclonal Antibodies

Tocilizumab + Atezolizumab + Radiation Therapy for Glioblastoma

Phase 2

Recruiting

Led By Stephen J Bagley

Research Sponsored by National Cancer Institute (NCI)

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a combination of tocilizumab, atezolizumab, and precise radiation therapy in patients with recurrent glioblastoma. Tocilizumab reduces inflammation, atezolizumab boosts the immune system, and the radiation targets the tumor. The goal is to make the tumor more responsive to treatment and improve patient outcomes.

Who is the study for?

This trial is for adults with recurrent glioblastoma, a type of brain cancer, who've had prior radiation therapy. They must have adequate organ function and not be pregnant or nursing. Participants need to agree to use contraception and can't have certain infections, autoimmune diseases, or recent treatments that could affect the immune system.

What is being tested?

The study tests if adding tocilizumab (an antibody targeting inflammation) and atezolizumab (an immunotherapy drug) to fractionated stereotactic radiation therapy is more effective in treating recurrent glioblastoma than radiation alone.

What are the potential side effects?

Potential side effects include reactions related to the immune system such as inflammation in various organs, infusion-related reactions like fever or chills, increased risk of infection due to immune suppression, and possible liver issues.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Dose-limiting toxicities (Safety Run-In)

Objective radiographic response rate (Phase II, Non-Surgical Cohort)

Secondary study objectives

Incidence of adverse events (Surgical Cohort and Non-Surgical Cohort)

Overall survival (Phase II, Non-Surgical Cohort)

Overall survival (Phase II, Surgical Cohort)

+2 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

3Treatment groups

Experimental Treatment

Group I: Group II, Arm II (tocilizumab, atezolizumab, FSRT, surgery)Experimental Treatment6 Interventions

Patients receive systemic treatment with atezolizumab IV over 30-60 minutes on day 1. Within 3-7 days, patients undergo FSRT for 3-5 fractions over 3-5 days. Within 7-14 days after FSRT, patients undergo surgery. Within 21-24 days from the first dose of systemic treatment, patients resume treatment with tocilizumab IV over 60 minutes with or without atezolizumab. Treatment repeats every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo MRI and tumor tissue collection on study. Patients undergo MRI throughout the trial, as well as blood sample and tumor tissue collection on study.

Group II: Group II, Arm I (tocilizumab, atezolizumab, FSRT, surgery)Experimental Treatment6 Interventions

Patients receive systemic treatment with tocilizumab IV over 60 minutes with or without atezolizumab IV over 30-60 minutes on day 1. Within 3-7 days, patients undergo FSRT for 3 fractions over 3-5 days. Within 7-14 days after FSRT, patients undergo surgery. Within 21-24 days from the first dose of systemic treatment, patients resume treatment with tocilizumab with or without atezolizumab. Treatment repeats every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo MRI throughout the trial, as well as blood sample and tumor tissue collection on study.

Group III: Group I (tocilizumab, atezolizumab, FSRT)Experimental Treatment4 Interventions

Patients receive systemic treatment with tocilizumab IV over 60 minutes with or without atezolizumab IV over 30-60 minutes on day 1. Within 3-7 days, patients undergo FSRT for 3 fractions over 3-5 days in the absence of disease progression or unacceptable toxicity. Starting 4 weeks from the first dose of systemic treatment, patients resume treatment with tocilizumab with or without atezolizumab. Treatment repeats every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo MRI throughout the trial.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Conventional Surgery

2006

Completed Phase 3

~1080

Tocilizumab

2012

Completed Phase 4

~1840

Atezolizumab

2016

Completed Phase 3

~5860

Magnetic Resonance Imaging

2017

Completed Phase 3

~1160

Biospecimen Collection

2004

Completed Phase 3

~2020

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Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Tocilizumab, an IL-6 receptor antagonist, reduces inflammation and immune suppression around the tumor, potentially enhancing the effectiveness of other treatments. Atezolizumab, a PD-L1 inhibitor, blocks the interaction between PD-L1 on tumor cells and PD-1 on T-cells, boosting the immune system's ability to attack the tumor. Fractionated Stereotactic Radiation Therapy delivers precise, high-dose radiation to the tumor, minimizing damage to surrounding healthy tissue. These mechanisms are vital for Glioblastoma patients as they aim to improve immune response effectiveness and reduce tumor growth while minimizing side effects.