Radiosurgery + Immunotherapy for Breast Cancer Brain Metastases

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must not be taking: Immunosuppressants, AntiPD-1, AntiPD-L1, others

Disqualifiers: Leptomeningeal disease, Autoimmune disease, others

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

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether combining stereotactic radiosurgery (SRS) with the immunotherapy drug Nivolumab can enhance treatment response in patients with breast cancer that has spread to the brain. The researchers aim to determine if this approach can more effectively target and shrink tumors. Patients with breast cancer and brain metastases, who have 10 or fewer tumors treatable with SRS, are suitable candidates. The trial seeks to improve outcomes for this challenging condition. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants an opportunity to contribute to groundbreaking research.

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

The trial allows you to continue using hormonal therapy or HER2-targeted therapy if your brain metastases progress during treatment. The protocol does not specify about other medications, so it's best to discuss your current medications with the study team.

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

Research has shown that using Nivolumab with stereotactic radiosurgery (SRS) is safe for treating breast cancer that has spread to the brain. Studies have found this treatment to be safe and practical, with no reported cases of radiation damage to brain tissue over a long period. Patients generally tolerate the treatment well.

Nivolumab is already used for other health issues, and research supports its use with SRS in this context, showing positive results. Specifically, these results include effective control of brain cancer and survival without new cancer growths in the brain.

Overall, research supports the safety and potential effectiveness of using Nivolumab with SRS for treating breast cancer that has spread to the brain. This information should reassure participants about the safety of joining trials with these treatments. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for breast cancer brain metastases, which often include surgery, whole-brain radiation therapy, or chemotherapy, the combination of Nivolumab and stereotactic radiosurgery (SRS) offers a unique approach. Nivolumab is an immunotherapy drug that boosts the body's immune system to target cancer cells, and it’s given intravenously every four weeks. This is followed by SRS, a precise form of radiation that focuses high doses on the tumor while sparing surrounding healthy tissue. Researchers are excited about this combination because it potentially enhances the immune response against cancer cells while minimizing damage to the rest of the brain, offering a promising alternative to traditional treatments.

What evidence suggests that this trial's treatments could be effective for breast cancer brain metastases?

Research has shown that combining Nivolumab with stereotactic radiosurgery (SRS) offers a promising treatment for breast cancer patients with brain metastases. In this trial, participants will receive Nivolumab followed by SRS. Studies have found this combination to be safe and practical, with no cases of radiation damage reported in long-term follow-ups. Nivolumab, an immunotherapy drug, helps the body's immune system identify and destroy cancer cells. SRS, a precise form of radiation therapy, has effectively controlled brain tumors and prevented their spread, particularly in certain types of breast cancer like triple-negative. Overall, this combination aims to enhance the body's ability to fight tumors and improve patient response to treatment. ^{1 2 6 7 8}

Who Is on the Research Team?

Kamran Ahmed, MD

Principal Investigator

H. Lee Moffitt Cancer Center and Research Institute

Are You a Good Fit for This Trial?

This trial is for adults with breast cancer that has spread to the brain. They must have had prior chemotherapy, no more than 10 brain metastases suitable for stereotactic radiosurgery (SRS), and a good performance status. Pregnant or breastfeeding women, those with leptomeningeal disease, previous whole-brain radiation therapy, certain viral infections, or inadequate organ function are excluded.

Inclusion Criteria

Provides signed and dated informed consent

WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug(s), plus 5 half-lives of study drug (half-life up to 25 days), plus 30 days (duration of ovulatory cycle) for a total of 5 months after treatment completion.

I can provide a sample of my tumor for testing, or have tried to.

Exclusion Criteria

I have a history of testing positive for HIV or AIDS.

Current or prior participation in a study of an investigational agent or investigational device within 2 weeks of first dose of study treatment

I am not allergic to any of the drugs or their components used in this study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 480 mg Nivolumab intravenously every 4 weeks, followed by stereotactic radiosurgery (SRS) the week after the initial dose

8 weeks

1 visit (in-person) every 4 weeks for Nivolumab, 1 visit (in-person) for SRS

Safety Observation

Participants are monitored for dose limiting toxicities, with an 8-week safety observation period

8 weeks

Follow-up

Participants are monitored for intracranial and extracranial progression-free survival and overall survival

Up to 24 months

What Are the Treatments Tested in This Trial?

Interventions

• Nivolumab
• Stereotactic Radiosurgery

Trial Overview The study tests if giving SRS after Nivolumab improves tumor response in patients with metastatic breast cancer in the brain. It aims to see whether this combination can better manage brain tumors compared to current treatments.

How Is the Trial Designed?

Group I: Nivolumab followed by stereotactic radiosurgery (SRS) Experimental Treatment 2 Interventions

480 mg Nivolumab will be given intravenously every 4 weeks, followed by SRS the week after the initial dose of Nivolumab.

Nivolumab is already approved in United States, European Union, Canada, Switzerland for the following indications:

Approved in United States as Opdivo for:

• Advanced or metastatic gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma
• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Hepatocellular carcinoma
• Esophageal squamous cell carcinoma

Approved in European Union as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Canada as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Switzerland as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40295143/

long-term results and biomarker analysis from a non ... - PubMed Nivolumab and SRS is a safe and feasible treatment option in BCBM. Long-term follow-up revealed no cases of radiation necrosis.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12039042/

Nivolumab and stereotactic radiosurgery for patients with ... Results. A total of 12 patients received SRS to 17 brain metastases. Breast cancer subtypes included triple negative (50%), hormone receptor (HR)+/ ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0960977624000882

The influence of immunotherapy and prognostic factors SRS demonstrates favourable outcomes in terms of local control and distant brain metastasis-free survival in TNBC.

4. mdpi.com mdpi.com/2072-6694/16/20/3551

Stereotactic Radiosurgery for Intracranial Breast Metastases Some studies have shown comparable outcomes for patients with 5–10 metastases treated with SRS compared to those with 1–4 lesions [45]. While ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03807765

NCT03807765 | Stereotactic Radiation and Nivolumab in ... This study is to find out if administration of stereotactic radiosurgery (SRS) given after Nivolumab will improve overall response rate/anti-tumor activity in ...

6. thebreastonline.com thebreastonline.com/article/S0960-9776(24)00088-2/fulltext

The influence of immunotherapy and prognostic factors SRS demonstrates favourable outcomes in terms of local control and distant brain metastasis-free survival in TNBC.

7. asco.org asco.org/abstracts-presentations/ABSTRACT340863

Nivolumab and stereotactic radiosurgery for patients with ... Conclusions: Nivolumab and SRS is a safe and feasible treatment option in breast cancer brain metastases. Preliminary studies reveal activity in certain ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8655428/

Nivolumab and Stereotactic Radiosurgery for Patients With ... Nivolumab and SRS is a safe and feasible treatment option in breast cancer brain metastases. Preliminary data reveals activity in certain breast cancer patients ...