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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for individuals with triple-negative breast cancer that has spread to the brain. It combines atezolizumab (Tecentriq), which aids the immune system in fighting cancer, with a precise radiation therapy called stereotactic radiosurgery (SRS). The trial seeks participants with this specific breast cancer type and brain tumors treatable with SRS, who have previously undergone other cancer treatments. Those meeting these conditions might find this trial suitable. As a Phase 2 trial, it measures the treatment's effectiveness in an initial, smaller group, providing an opportunity to contribute to important research.

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.

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

Research shows that combining atezolizumab with stereotactic radiosurgery (SRS) to treat brain tumors in breast cancer patients is generally well-tolerated. The FDA has already approved atezolizumab for other cancer types, indicating its safety is well understood. Studies have found this combination promising, with manageable side effects.

SRS, a precise radiation therapy, has effectively treated brain tumors with few serious side effects. Some studies have reported a low rate of radiation necrosis (tissue damage from radiation), about 3%, when SRS is used with similar drugs, suggesting the treatment is relatively safe.

Overall, while side effects can occur, the combination of atezolizumab and SRS has demonstrated a safety profile that supports further research in clinical trials. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using atezolizumab with stereotactic radiosurgery (SRS) for treating breast cancer with brain metastases because it leverages a novel approach. Unlike traditional treatments like chemotherapy and whole-brain radiation, which can affect the entire body and brain, this combination specifically targets cancer cells. Atezolizumab, an immunotherapy drug, works by boosting the body's immune system to attack cancer cells more effectively. Meanwhile, SRS delivers precise, high-dose radiation directly to the brain tumor, potentially reducing side effects and sparing healthy brain tissue. This targeted approach could lead to more effective and less harmful outcomes for patients.

What evidence suggests that the combination of atezolizumab and stereotactic radiosurgery could be effective for breast cancer with brain tumor?

Research has shown that combining atezolizumab with stereotactic radiosurgery (SRS) may help treat cancers that have spread to the brain. In this trial, participants will receive both atezolizumab and SRS. Atezolizumab blocks a protein called PD-L1, enabling the immune system to find and attack cancer cells. SRS is a type of radiation therapy that precisely targets brain tumors. Studies with similar treatment combinations have demonstrated improved survival rates, suggesting that these treatments together could effectively combat breast cancer that has spread to the brain. ^{1 2 3 6 7}

Who Is on the Research Team?

Nancy Lin

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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, 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03483012

NCT03483012 | Atezolizumab + Stereotactic Radiation in ... By blocking the PD-L1 pathway, Atezolizumab may help the immune system identify and catch tumor cells. Stereotactic radiosurgery (SRS) is a standard procedure ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40379142/

Atezolizumab and Stereotactic Body Radiation in Metastatic ... In this first trial of SBRT and atezolizumab in metastatic cervical cancer unselected for PD-L1, combination therapy was well tolerated.

3. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK594965/

Combined Stereotactic Radiosurgery and Immune Checkpoint ... The results of 75 MM patients with 566 brain metastases who received SRS and ICIs were examined. The authors considered SRS and ICIs to be concurrent if SRS was ...

4. redjournal.org redjournal.org/article/S0360-3016(24)00006-3/fulltext

Immunotherapy and Radiation Therapy Sequencing in ... Similarly, improved survival was seen in patients with BC and brain metastases treated with stereotactic radiosurgery (SRS).

5. researchgate.net researchgate.net/publication/363521763_1145P_Atezolizumab_and_stereotactic_body_radiotherapy_in_patients_with_advanced_non-small_cell_lung_cancer_The_ComIT-1_trial

1145P Atezolizumab and stereotactic body radiotherapy in ... Adjuvant chemotherapy improves overall survival (OS) following stereotactic body radiotherapy (SBRT) in patients with early stage non-small cell ...

6. dana-farber.org dana-farber.org/clinical-trials/17-519

A phase II study of atezolizumab in combination with ... This research study is studying the combination of a drug called atezolizumab and a radiation procedure called stereotactic radiosurgery (SRS) as a possible ...

7. mdpi.com mdpi.com/2227-9059/10/9/2211

Treatment of Brain Metastases: The Synergy ... The overall incidence of radiation necrosis with concurrent ipilimumab was 3%, suggesting that the combination of radiosurgery and ipilimumab is relatively safe ...