Tocilizumab + Atezolizumab + Radiation Therapy for Glioblastoma

Not currently recruiting at 123 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Anti-PD-1, Anti-PD-L1, Anti-CTLA-4, others

Disqualifiers: IDH mutation, Bevacizumab, Transplant, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 30

Duration: 4 weeks per cycle, up to 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore the effectiveness of combining tocilizumab, atezolizumab, and radiation therapy in treating glioblastoma that has returned after initial treatment. Tocilizumab and atezolizumab are antibodies that may help the immune system fight cancer by reducing inflammation and attacking tumor cells. The researchers aim to determine if this combination improves the tumor's response to treatment. Patients with recurrent glioblastoma and tumors suitable for precise radiation may be ideal candidates for this trial. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in glioblastoma treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, certain medications like systemic immunosuppressive agents and corticosteroids above a specific dose must be stopped before joining the trial. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that tocilizumab and atezolizumab have generally been well-tolerated in past studies. Tocilizumab targets a protein called interleukin-6 (IL-6) and is already approved for other conditions, indicating its safety is well understood. Atezolizumab, an immunotherapy used in various cancers, has a safety record considered manageable.

Studies have identified common side effects of tocilizumab, such as headaches and high blood pressure, which are usually mild. Atezolizumab can sometimes cause tiredness or skin reactions, but serious side effects are rare. The radiation therapy used with these drugs is precise, minimizing harm to healthy tissue.

Overall, this combination is under study to determine its effectiveness in treating glioblastoma, with a strong focus on safety. Specifically, previous patients have shown promising results, with tumors shrinking or stabilizing while keeping side effects manageable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of tocilizumab, atezolizumab, and radiation therapy for glioblastoma because it offers a new approach to tackling this aggressive brain cancer. Unlike traditional treatments, which often include surgery, radiation, and chemotherapy, this treatment harnesses the power of the immune system by using atezolizumab, an immunotherapy drug that targets the PD-L1 protein to help the immune system attack cancer cells. Tocilizumab, on the other hand, is an anti-inflammatory drug that may reduce the side effects of cancer treatment and improve outcomes. Additionally, the use of Fractionated Stereotactic Radiation Therapy (FSRT) allows for precise targeting of the tumor, potentially reducing damage to surrounding healthy tissue. This innovative combination aims to enhance treatment effectiveness while minimizing side effects, setting it apart from existing standard therapies.

What evidence suggests that this trial's treatments could be effective for glioblastoma?

This trial evaluates the combination of three treatments for recurrent glioblastoma, a type of brain cancer. Participants will receive tocilizumab, atezolizumab, and fractionated stereotactic radiation therapy (FSRT) in different treatment arms. Tocilizumab targets a protein called interleukin-6 (IL-6), which can reduce inflammation and may make tumors more responsive to other treatments. Atezolizumab is an immunotherapy drug that helps the body's immune system attack cancer cells. Studies have shown that FSRT can improve survival rates by precisely targeting the tumor with radiation. Combining these treatments may lead to better outcomes than using radiation therapy alone. Initial findings suggest this combination could shrink or stabilize tumors more effectively. ^{6 7 8 9 10}

Who Is on the Research Team?

Stephen J Bagley

Principal Investigator

NRG Oncology

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

Specific intervals from previous treatments to registration are required to be eligible

I have been diagnosed with glioblastoma.

My cancer has returned for the first time after initial radiation treatment.

Exclusion Criteria

My tumor has a mutation in the IDH1 or IDH2 gene.

I have a genetic defect in DNA repair.

History or risk of autoimmune disease

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Run-In

Patients receive systemic treatment with tocilizumab with or without atezolizumab and undergo FSRT. Treatment repeats every 4 weeks for up to 2 years.

4 weeks per cycle, up to 2 years

Multiple visits for treatment and monitoring

Treatment

Patients receive systemic treatment with tocilizumab and atezolizumab, undergo FSRT, and may undergo surgery. Treatment repeats every 4 weeks for up to 2 years.

4 weeks per cycle, up to 2 years

Multiple visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

Up to 2 years

Follow-up visits at 30 days, 3, 6, 9, 12, 18, and 24 months

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• Fractionated Stereotactic Radiation Therapy
• Tocilizumab

Trial Overview 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.

How Is the Trial Designed?

Group I: Group II, Arm II (tocilizumab, atezolizumab, FSRT, surgery) Experimental Treatment 6 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 21-42 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 Treatment 6 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 Treatment 4 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.

Atezolizumab is already approved in United States, European Union for the following indications:

Approved in United States as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Approved in European Union as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

NRG Oncology

Collaborator

Trials

242

Recruited

105,000+

Published Research Related to This Trial

In a study of 103 glioblastoma patients treated with standard temozolomide and radiotherapy, the median overall survival was found to be 13.7 months, highlighting the effectiveness of this treatment regimen.

Three key prognostic factors were identified that negatively impacted overall survival: age over 65 years, a Medical Research Council (MRC) scale score of 3-4, and the occurrence of postoperative complications, suggesting that these factors can help predict patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Age, Neurological Status MRC Scale, and Postoperative Morbidity are Prognostic Factors in Patients with Glioblastoma Treated by Chemoradiotherapy. Verlut, C., Mouillet, G., Magnin, E., et al.[2020]

Fractionated stereotactic re-irradiation shows a 12-month overall survival rate of 33.1% and a progression-free survival rate of 13.4% in patients with recurrent glioblastoma, based on a meta-analysis of eight studies involving 307 patients.

The treatment has a low incidence of radiation necrosis, indicating it is a relatively safe option for patients, with factors like age and radiation dose affecting survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fractionated stereotactic re-irradiation for recurrent glioblastoma: A systematic review and meta-analysis. Luo, T., Feng, J., Sun, P.[2023]

In a study of 25 patients with recurrent gliomas, the combination of fractionated stereotactic radiotherapy (FSRT) and daily temozolomide (TMZ) demonstrated a median overall survival of 59 months, indicating its effectiveness as a treatment option.

The treatment was well-tolerated, with no severe side effects reported, suggesting that this approach is safe for patients undergoing re-irradiation for recurrent gliomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiochemotherapy with temozolomide as re-irradiation using high precision fractionated stereotactic radiotherapy (FSRT) in patients with recurrent gliomas. Combs, SE., Bischof, M., Welzel, T., et al.[2022]

The combination of pembrolizumab, hypofractionated stereotactic irradiation (HFSRT), and bevacizumab was found to be generally safe and well tolerated in 32 patients with recurrent high-grade gliomas, with manageable treatment-related adverse events such as proteinuria and fatigue.

In the bevacizumab-naïve group, 83% of patients showed a complete or partial response, with a median overall survival of 13.45 months, indicating promising preliminary efficacy of this treatment combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypofractionated stereotactic re-irradiation with pembrolizumab and bevacizumab in patients with recurrent high-grade gliomas: results from a phase I study. Sahebjam, S., Forsyth, PA., Tran, ND., et al.[2021]

In a study involving 20 patients with recurrent malignant gliomas, hypofractionated stereotactic radiotherapy (H-SRT) demonstrated a low toxicity profile, with no grade 3 toxicities or reoperations required due to treatment-related complications.

The study found that higher total doses of H-SRT (30 Gy and 35 Gy) were associated with a significantly better response rate (79%) compared to lower doses, suggesting that dose escalation could enhance treatment efficacy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I dose escalation study of hypofractionated stereotactic radiotherapy as salvage therapy for persistent or recurrent malignant glioma. Hudes, RS., Corn, BW., Werner-Wasik, M., et al.[2022]

Tipifarnib can be safely administered at a maximum tolerated dose of 300 mg twice daily in combination with conventional radiotherapy for newly diagnosed glioblastoma patients, with manageable side effects like rash and fatigue.

In a specific cohort receiving both tipifarnib and temozolomide, 65% of patients were alive after one year, suggesting potential efficacy that warrants further investigation in a Phase II study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I trial of tipifarnib with radiation therapy, with and without temozolomide, for patients with newly diagnosed glioblastoma. Nghiemphu, PL., Wen, PY., Lamborn, KR., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12034766/

Improved overall survival in an anti-PD-L1 treated cohort of ... In this study the concurrent use of atezolizumab (anti-PD-L1) with radiation and TMZ was tolerable and demonstrated efficacy in line with ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/30073642/

Clinical activity and safety of atezolizumab in patients with ... The median overall survival was 4.2 months (range 1.2 to 18.8+ months). Association between peripheral CD4+ T cells and efficacy was observed.

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2020.38.15_suppl.2511

Phase I/II study to evaluate the safety and clinical efficacy ... With median follow-up time of 16.7 months (data cutoff = 30 Dec 2019), 24 patients had died and 32 had progressed. Median OS was 17.1 months (95 ...

4. nature.com nature.com/articles/s41423-024-01226-x

Immunotherapy for glioblastoma: current state, challenges ... The treatment outcomes have remained largely unchanged in recent decades, and most GBM patients experience tumor recurrence. The unique location ...

5. braintumorcenter.ucsf.edu braintumorcenter.ucsf.edu/clinical-trial/multicenter-trial-identify-optimal-atezolizumab-biomarkers-setting-recurrent

The MOAB Trial | UCSF Brain Tumor Center In this phase II study, researchers will study whether treatment with atezolizumab provides a therapeutic benefit for patients with recurrent glioblastoma ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04729959

Study Details | NCT04729959 | Testing the Addition of the ... Combination therapy with tocilizumab, atezolizumab and fractionated stereotactic radiation therapy may shrink or stabilize the cancer better than radiation ...

7. nrgoncology.org nrgoncology.org/Home/News/Post/a-safety-run-in-and-phase-ii-study-evaluating-the-efficacy-safety-and-impact-on-the-tumor-microenvironment-of-the-combination-of-tocilizumab-atezolizumab-and-fractionated-stereotactic-radiotherapy-in-recurrent-glioblastoma-nrg-bn010

A Safety Run-in and Phase II Study Evaluating the Efficacy ... The primary objective of Phase II is to determine the efficacy of the combination of tocilizumab (anti-IL6R), atezolizumab (anti-PD-L1), and FSRT in recurrent ...

8. academic.oup.com academic.oup.com/neuro-oncology/article/24/Supplement_7/vii64/6826159

CTIM-21. NRG-BN010: A SAFETY RUN-IN AND PHASE II ... Additional preclinical data suggest that fractionated stereotactic radiotherapy (FSRT) can stimulate the release and presentation of tumor- ...

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Clinical Trials Combination therapy with tocilizumab, atezolizumab and fractionated stereotactic radiation therapy may shrink or stabilize the cancer better than radiation ...

10. withpower.com withpower.com/trial/tocilizumab-atezolizumab-radiation-therapy-for-glioblastoma-08724

Tocilizumab + Atezolizumab + Radiation Therapy for ... This trial tests a combination of tocilizumab, atezolizumab, and precise radiation therapy in patients with recurrent glioblastoma.