Tocilizumab + Atezolizumab + Radiation Therapy for Glioblastoma

Recruiting at 120 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

53 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

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.

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 the combination of Tocilizumab, Atezolizumab, and Radiation Therapy safe for humans?

The safety of fractionated stereotactic radiation therapy (a type of precise radiation treatment) has been studied in various trials for glioblastoma, showing it can be used safely, though side effects may occur. Tocilizumab and Atezolizumab have been used in other conditions, generally showing a manageable safety profile, but combining them with radiation therapy for glioblastoma specifically may have different safety considerations that are not fully known. ^{1 2 3 4 5}

How is the treatment of Tocilizumab + Atezolizumab + Radiation Therapy for Glioblastoma different from other treatments?

This treatment is unique because it combines immunotherapy drugs (Tocilizumab and Atezolizumab) with targeted radiation therapy, aiming to enhance the immune system's ability to fight glioblastoma, which is different from the standard approach of using chemotherapy with temozolomide and radiation. ^{6 7 8 9 10}

What data supports the effectiveness of the treatment Tocilizumab + Atezolizumab + Radiation Therapy for Glioblastoma?

Research suggests that fractionated stereotactic radiotherapy (FSRT) can be effective for recurrent glioblastoma, especially when combined with other treatments like chemotherapy or immunotherapy, which may help improve survival. Additionally, combining radiation with anti-PDL1 treatments, similar to Atezolizumab, has shown potential benefits in treating recurrent glioblastoma. ^{4 11 12 13 14}

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.

I have a significant liver condition.

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 21-24 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 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

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]

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]

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 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]

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]

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]

Citations

1. Switzerland pubmed.ncbi.nlm.nih.gov

Re-Irradiation with Stereotactic Radiosurgery/Radiotherapy for Recurrent High-Grade Gliomas: Improved Survival in the Modern Era. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

A phase I trial of tipifarnib with radiation therapy, with and without temozolomide, for patients with newly diagnosed glioblastoma. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Radiochemotherapy with temozolomide as re-irradiation using high precision fractionated stereotactic radiotherapy (FSRT) in patients with recurrent gliomas. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Salvage Fractionated Stereotactic Radiotherapy with or without Chemotherapy and Immunotherapy for Recurrent Glioblastoma Multiforme: A Single Institution Experience. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Hypofractionated Stereotactic Re-irradiation and Anti-PDL1 Durvalumab Combination in Recurrent Glioblastoma: STERIMGLI Phase I Results. [2023]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Fractionated stereotactic re-irradiation for recurrent glioblastoma: A systematic review and meta-analysis. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

A phase II trial of accelerated radiotherapy using weekly stereotactic conformal boost for supratentorial glioblastoma multiforme: RTOG 0023. [2018]

8. United States pubmed.ncbi.nlm.nih.gov

A pilot study of hypofractionated stereotactic radiation therapy and sunitinib in previously irradiated patients with recurrent high-grade glioma. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

A phase I dose escalation study of hypofractionated stereotactic radiotherapy as salvage therapy for persistent or recurrent malignant glioma. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Age, Neurological Status MRC Scale, and Postoperative Morbidity are Prognostic Factors in Patients with Glioblastoma Treated by Chemoradiotherapy. [2020]

11. United States pubmed.ncbi.nlm.nih.gov

Radiation and Immunotherapy in High-grade Gliomas: Where Do We Stand? [2022]

12. England 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. [2021]

13. England pubmed.ncbi.nlm.nih.gov

Radiation and concomitant chemotherapy for patients with glioblastoma multiforme. [2021]

14. Japan pubmed.ncbi.nlm.nih.gov

Feasibility evaluation of hypofractionated radiotherapy with concurrent temozolomide in elderly patients with glioblastoma. [2018]