Atezolizumab + Stereotactic Radiation for Breast Cancer with Brain Tumor

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Dana-Farber Cancer Institute

Must not be taking: High-dose corticosteroids, Immunosuppressants

Disqualifiers: CNS complications, Leptomeningeal metastases, Uncontrolled illness, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 1.5 years

6 Participants Needed

Trial Summary

What is the purpose of this trial?

This research study is studying the combination of a drug called atezolizumab and a radiation procedure called stereotactic radiosurgery (SRS) as a possible treatment for triple-negative breast cancer that has spread to the brain. The interventions involved in this study are: * Atezolizumab * Stereotactic radiosurgery (SRS)

Do I have to stop taking my current medications for the trial?

Yes, you must stop taking any systemic therapy at least 14 days before starting the trial treatment. However, you can continue or start bisphosphonate therapy during the study.

What data supports the effectiveness of the treatment Atezolizumab combined with Stereotactic Radiation for Breast Cancer with Brain Tumor?

Research shows that combining atezolizumab, an immune checkpoint inhibitor, with radiation therapy can be safe and potentially effective, as seen in studies with other cancers like non-small cell lung cancer and bladder cancer. These studies suggest that the combination may enhance the body's immune response against tumors, although more research is needed to confirm these effects specifically for breast cancer with brain tumors. ^{1 2 3 4 5}

Is the combination of Atezolizumab and stereotactic radiation generally safe for humans?

Atezolizumab, when combined with stereotactic radiation, has been studied in different cancers and is generally well tolerated. In a study with lung cancer patients, the treatment was well tolerated, and the maximum tolerated dose of Atezolizumab was established. Additionally, Atezolizumab has been approved for use in various cancers, indicating its safety profile has been evaluated in multiple settings. ^{2 3 6 7 8}

How is the treatment of Atezolizumab combined with stereotactic radiation unique for breast cancer with brain tumors?

This treatment is unique because it combines Atezolizumab, an immune checkpoint inhibitor that boosts the body's immune response against cancer, with stereotactic radiation, a precise form of radiation therapy. This combination aims to enhance the effectiveness of treatment for breast cancer with brain tumors, a condition with limited standard treatment options. ^{2 3 5 9 10}

Research Team

Nancy Lin

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

This trial is for adults with triple-negative breast cancer that has spread to the brain. They must have stable brain metastases treatable with SRS, controlled steroid use, measurable disease outside the brain, and normal organ function. Pregnant women or those on high-dose steroids, previous anti-PD-1/PD-L1 therapy, or with certain medical conditions are excluded.

Inclusion Criteria

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

I've been on a stable dose of dexamethasone (2mg or less) for at least a week.

My organs and bone marrow are functioning normally.

Exclusion Criteria

I have a serious illness that is not under control.

My cancer has spread to the brain or its coverings.

I haven't taken high doses of steroids like dexamethasone (>2mg/day) in the last week.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive atezolizumab intravenously once every 3 weeks and stereotactic radiosurgery (SRS) begins within 14 days after brain MRI

Up to 1.5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term follow-up

Participants are monitored for overall survival

Up to 3.8 years

Treatment Details

Interventions

• Atezolizumab
• Stereotactic Radiosurgery (SRS)

Trial Overview The study tests combining atezolizumab (a drug) with stereotactic radiosurgery (SRS), a precise radiation procedure for treating brain tumors in patients whose breast cancer has spread to the brain.

Participant Groups

Group I: Atezolizumab + Stereotactic radiosurgery (SRS) Experimental Treatment 2 Interventions

* Atezolizumab administered intravenously once every 3 weeks * Stereotactic radiosurgery (SRS) begin within 14 days after brain MRI obtained

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?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Findings from Research

Combining anti-HER2 monoclonal antibodies like trastuzumab and pertuzumab with radiation therapy appears to be safe, showing no significant increase in toxicity based on the reviewed literature.

However, caution is advised when combining radiation with tyrosine kinase inhibitors (like lapatinib and tucatinib) and certain antibody-drug conjugates, as the safety of these combinations is not well established.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interaction between Radiation Therapy and Targeted Therapies in HER2-Positive Breast Cancer: Literature Review, Levels of Evidence for Safety and Recommendations for Optimal Treatment Sequence. Debbi, K., Grellier, N., Loganadane, G., et al.[2023]

In a phase I study involving 20 patients with early-stage non-small cell lung cancer, the combination of stereotactic ablative radiotherapy (SABR) and the immune-checkpoint inhibitor atezolizumab was well tolerated, with the maximum tolerated dose established at 1200 mg.

Early efficacy signals were observed, with 17% of patients showing responses after two cycles of atezolizumab before starting SABR, and specific biomarkers indicating T cell activation were found to be predictive of treatment benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab plus stereotactic ablative radiotherapy for medically inoperable patients with early-stage non-small cell lung cancer: a multi-institutional phase I trial. Monjazeb, AM., Daly, ME., Luxardi, G., et al.[2023]

In a phase 2 study involving 45 patients with invasive bladder cancer, the combination of radiation therapy and atezolizumab resulted in a high pathologic complete response (pCR) rate of 84.4%, particularly in older patients and those with high PD-L1 expression.

The treatment was associated with acceptable toxicity, with 93.3% of patients experiencing adverse events, mostly mild to moderate, and only 13.3% experiencing grade 3 adverse events, indicating that this approach could be a viable bladder-preserving option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Bladder Preservation Therapy in Combination with Atezolizumab and Radiation Therapy (BPT-ART) for Invasive Bladder Cancer: Interim Analysis from a Multicenter, Open-label, Prospective Phase 2 Trial. Kimura, T., Ishikawa, H., Nagumo, Y., et al.[2023]

The TREASURE trial is a phase II clinical study involving 104 patients with extensive disease small cell lung cancer (SCLC) to evaluate the effectiveness of adding thoracic radiotherapy (TRT) to atezolizumab maintenance therapy after initial chemo-immunotherapy, with overall survival as the primary endpoint.

This trial aims to enhance treatment outcomes by exploring the synergistic effects of combining immunotherapy with radiotherapy, while also assessing safety and collecting biomarker samples for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protocol of the TREASURE study: Thoracic RadiothErapy with Atezolizumab in Small cell lUng canceR Extensive disease - a randomized, open-label, multicenter phase II trial. Bozorgmehr, F., Christopoulos, P., Chung, I., 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]

Atezolizumab is a monoclonal antibody that targets PD-L1, which is being developed for treating various blood cancers and solid tumors, showing promise in cancer immunotherapy.

It has already been approved in the US as a second-line treatment for urothelial carcinoma and is pending approval for non-small cell lung cancer, highlighting its potential efficacy in these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: First Global Approval. Markham, A.[2019]

Atezolizumab, the first anti-PD-L1 monoclonal antibody approved by the FDA, has shown promising efficacy in treating metastatic triple-negative breast cancer, supported by data from the Phase III IMpassion130 trial.

The review highlights the pharmacodynamic and pharmacokinetic properties of atezolizumab, emphasizing its safety and effectiveness in various cancers, including small-cell lung cancer and renal cell cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab for use in PD-L1-positive unresectable, locally advanced or metastatic triple-negative breast cancer. Mavratzas, A., Seitz, J., Smetanay, K., et al.[2020]

Atezolizumab (Tecentriq) is an FDA-approved treatment for unresectable or metastatic alveolar soft part sarcoma (ASPS), showing a 24% overall response rate in a clinical trial with 49 patients, and a durable response rate of 67% at 6 months and 42% at 12 months.

The treatment has a manageable safety profile, with common severe side effects including musculoskeletal pain (8%) and hypertension (6%), making it a viable option for patients with limited treatment alternatives for this high-risk disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab as the First Systemic Therapy Approved for Alveolar Soft Part Sarcoma. Bergsma, EJ., Elgawly, M., Mancuso, D., et al.[2023]

References

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

Interaction between Radiation Therapy and Targeted Therapies in HER2-Positive Breast Cancer: Literature Review, Levels of Evidence for Safety and Recommendations for Optimal Treatment Sequence. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Atezolizumab plus stereotactic ablative radiotherapy for medically inoperable patients with early-stage non-small cell lung cancer: a multi-institutional phase I trial. [2023]

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

Efficacy and Safety of Bladder Preservation Therapy in Combination with Atezolizumab and Radiation Therapy (BPT-ART) for Invasive Bladder Cancer: Interim Analysis from a Multicenter, Open-label, Prospective Phase 2 Trial. [2023]

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

Protocol of the TREASURE study: Thoracic RadiothErapy with Atezolizumab in Small cell lUng canceR Extensive disease - a randomized, open-label, multicenter phase II trial. [2022]

5. 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]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Atezolizumab: First Global Approval. [2019]

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

Atezolizumab for use in PD-L1-positive unresectable, locally advanced or metastatic triple-negative breast cancer. [2020]

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

Atezolizumab as the First Systemic Therapy Approved for Alveolar Soft Part Sarcoma. [2023]

9. Ireland pubmed.ncbi.nlm.nih.gov

Atezolizumab in patients with advanced non-small cell lung cancer and history of asymptomatic, treated brain metastases: Exploratory analyses of the phase III OAK study. [2019]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Recent advances in atezolizumab-based programmed death-ligand 1 (PD-L1) blockade therapy for breast cancer. [2022]