Atezolizumab + Radiation for Glioblastoma

Recruiting in Palo Alto (17 mi)

Overseen by Alexander M. Stessin

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase < 1

Recruiting

Sponsor: Stony Brook University

Must not be taking: Corticosteroids, Immunosuppressive, Immunostimulatory, others

Disqualifiers: Autoimmune disease, Cardiovascular disease, others

Stay on Your Current Meds

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot continue using high-dose corticosteroids or certain immune-related treatments.

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

Research shows that combining radiation with drugs that block PD1/PD-L1, like pembrolizumab, can be effective for high-grade brain tumors. Additionally, using precise radiation techniques, such as fractionated stereotactic radiotherapy (FSRT), has shown promise in treating recurrent glioblastoma, suggesting potential benefits for similar treatments.

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Is Atezolizumab safe for use in humans?

Atezolizumab has been studied for safety in patients with glioblastoma, showing clinical activity and being generally safe in humans, as reported in a phase 1a clinical trial.

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

This treatment combines atezolizumab, an immune checkpoint inhibitor that helps the immune system attack cancer cells, with fractionated stereotactic radiotherapy (FSRT), a precise form of radiation therapy. Unlike standard treatments, this approach leverages the potential synergy between immunotherapy and targeted radiation to enhance the immune response against glioblastoma, a brain cancer with limited treatment options.

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Eligibility Criteria

This trial is for patients with a new diagnosis of Glioblastoma Multiforme, a serious brain tumor. They must be candidates for surgery aiming to remove over 80% of the tumor, have good organ function and performance status (ECOG <=2), and not be pregnant. Exclusions include recent other cancers, severe infections or diseases, high steroid use, certain heart conditions, immune system issues like autoimmune disease or prior immunotherapy.

Inclusion Criteria

My organs are working well.

I can take care of myself but might not be able to do heavy physical work.

My tumor is 3.5 cm or smaller.

Exclusion Criteria

I have previously been treated with CD137 agonists or immune checkpoint inhibitors.

My cancer pain is not managed with current treatments.

My brain cancer has spread widely or affects both sides of my brain.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive fractionated stereotactic radiotherapy (FSRT) for 2 weeks, along with two doses of Atezolizumab at the beginning and end of the period

2 weeks

2 visits (in-person)

Surgery

Participants undergo craniotomy and maximal safe resection as per normal care for glioblastoma

Adjuvant Treatment

Participants follow normal care for glioblastoma in addition to Atezolizumab 840 mg IV every 2 weeks

Duration of adjuvant treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Participant Groups

The study tests Atezolizumab combined with FSRT radiation in treating Glioblastoma before and after surgical removal of the tumor. Patients will receive two doses of Atezolizumab along with two weeks of radiotherapy followed by surgery and then continue Atezolizumab every two weeks during adjuvant treatment.

Group I: Treatment Experimental Treatment 1 Intervention

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Stony Brook University Hospital Stony Brook, NY

Who Is Running the Clinical Trial?

Stony Brook University Lead Sponsor

Genentech, Inc. Industry Sponsor

References

1. 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] Radiotherapy may synergize with programmed cell death 1 (PD1)/PD1 ligand (PD-L1) blockade. The purpose of this study was to determine the recommended phase II dose, safety/tolerability, and preliminary efficacy of combining pembrolizumab, an anti-PD1 monoclonal antibody, with hypofractionated stereotactic irradiation (HFSRT) and bevacizumab in patients with recurrent high-grade gliomas (HGGs).

2. 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] To evaluate outcome after fractionated stereotactic radiotherapy (FSRT) and concomitant daily temozolomide (TMZ) in patients with recurrent gliomas.

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

Salvage reirradiation for recurrent glioblastoma with radiosurgery: radiographic response and improved survival. [2022] To determine the radiographic and clinical efficacy of stereotactic single dose radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT) as salvage therapy for glioblastoma (GBM) at recurrence.

4. England pubmed.ncbi.nlm.nih.gov

NRG/RTOG 0837: Randomized, phase II, double-blind, placebo-controlled trial of chemoradiation with or without cediranib in newly diagnosed glioblastoma. [2023] A randomized, phase II, placebo-controlled, and blinded clinical trial (NCT01062425) was conducted to determine the efficacy of cediranib, an oral pan-vascular endothelial growth factor receptor tyrosine kinase inhibitor, versus placebo in combination with radiation and temozolomide in newly diagnosed glioblastoma.

5. Greece pubmed.ncbi.nlm.nih.gov

Feasibility of Salvage Re-irradiation With Stereotactic Radiotherapy for Recurrent Glioma Using CyberKnife. [2019] To evaluate the toxicity and efficacy of re-irradiation with salvage stereotactic radiotherapy (SRT) for recurrent glioma using CyberKnife.

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

Clinical activity and safety of atezolizumab in patients with recurrent glioblastoma. [2020] Glioblastoma is the most common primary malignant brain tumor. No standard treatment exists for recurrent disease. Glioblastoma is associated with an immunosuppressive tumor microenvironment. Immune checkpoint inhibitors, including atezolizumab (anti-programmed death-ligand 1), have demonstrated clinical activity in various cancers. Here, we present the safety and efficacy of atezolizumab in patients with glioblastoma from the phase 1a PCD4989g clinical trial (NCT01375842).

7. England pubmed.ncbi.nlm.nih.gov

Nivolumab plus radiotherapy with or without temozolomide in newly diagnosed glioblastoma: Results from exploratory phase I cohorts of CheckMate 143. [2023] The phase 1 cohorts (1c+1d) of CheckMate 143 (NCT02017717) evaluated the safety/tolerability and efficacy of nivolumab plus radiotherapy (RT) ± temozolomide (TMZ) in newly diagnosed glioblastoma.

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

A phase I dose-escalation study (ISIDE-BT-1) of accelerated IMRT with temozolomide in patients with glioblastoma. [2018] To determine the maximum tolerated dose (MTD) of fractionated intensity-modulated radiotherapy (IMRT) with temozolomide (TMZ) in patients with glioblastoma.

9. England pubmed.ncbi.nlm.nih.gov

Agonist anti-GITR monoclonal antibody and stereotactic radiation induce immune-mediated survival advantage in murine intracranial glioma. [2022] Glioblastoma (GBM) is a poorly immunogenic neoplasm treated with focused radiation. Immunotherapy has demonstrated synergistic survival effects with stereotactic radiosurgery (SRS) in murine GBM. GITR is a co-stimulatory molecule expressed constitutively on regulatory T-cells and by effector T-cells upon activation. We tested the hypothesis that anti-GITR monoclonal antibody (mAb) and SRS together would confer an immune-mediated survival benefit in glioma using the orthotopic GL261 glioma model.