Pembrolizumab and Stereotactic Radiosurgery for Breast Cancer Brain Metastases

Pembrolizumab And Stereotactic Radiosurgery (Srs) Of Selected Brain Metastases In Breast Cancer Patients

This study is testing if combining an immunotherapy drug called pembrolizumab with a targeted radiation treatment can help people with metastatic breast cancer who have multiple brain tumors.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 41 (estimated)
• Ages: 19 Years to 90 Years
• Sex: Female
• Sponsor: Weill Medical College of Cornell University (Academic / other)
• Drugs / interventions: pembrolizumab, radiation, prednisone
• Locations: 3 sites (New York, New York and 2 other locations)
• Trial ID: NCT03449238 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the combination of pembrolizumab, an immunotherapy drug, and stereotactic radiosurgery (SRS) in patients with metastatic breast cancer who have at least two brain metastases. Participants will receive pembrolizumab every three weeks and undergo SRS to one of their brain lesions. The treatment aims to assess the safety and efficacy of this combination approach, with patients monitored for disease progression or adverse effects. The trial will follow patients until death to gather comprehensive data on outcomes.

Who should consider this trial

Good fit: Ideal candidates include adults over 18 with metastatic breast cancer and at least two measurable brain metastases.

Not a fit: Patients with only one brain metastasis or those with significant prior treatments that affect eligibility may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve survival and quality of life for patients with metastatic breast cancer and brain metastases.

How similar studies have performed: Other studies have shown promising results with similar combinations of immunotherapy and radiation, suggesting potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

* Age older than 18
* Eastern Cooperative Oncology Group (ECOG) performance status 0-1
* Men and/or pre- or post-menopausal women with metastatic breast cancer with at least 2 intracranial untreated and measurable (≥ 3mm) metastases as visualized on brain MRI
* A diagnostic contrast enhanced MRI demonstrating at least 2 lesions in the brain, (≥3mm in size), performed within two weeks prior to treatment
* Maximum diameter of treated lesions should be \<4cm in size
* Have measurable disease based on RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
* Patient needs to be able to understand and demonstrate willingness to sign a written informed consent document
* Prior SRS is permitted, however the lesions targeted for treatment on trial need to be previously untreated by SRS
* Patients who have undergone prior subtotal resection are eligible providing that residual disease is \<4cm in maximum diameter: the cavity will be treated as standard of care.
* Continuing a concurrent use of hormonal therapy or anti-Her2 neu therapy is allowed, if the patient exhibits brain metastases progression during these treatments
* Enrolled patients should have a two-week washout period from last systemic treatment
* The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
* Contraception duration of 120 days
* Adequate bone marrow reserve and liver function

Exclusion Criteria:

* Active connective tissue disorders, such as lupus or scleroderma requiring flare therapy
* Patients who have undergone complete resection of all known brain metastases
* Inability to obtain histologic proof of breast cancer
* Target lesion metastasis within 5mm of the optic apparatus so that some portion of the optic nerve or chiasm would be included in the SRS field
* Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
* Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed.
* Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
* Has a known additional malignancy (second primary) that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
* Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
* Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
* Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis.
* Has an active infection requiring systemic therapy..Has a known history of Human Immunodeficiency Virus (HIV).
* Has a known history of Hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] reactive) or known active Hepatitis C virus (defined as HCV RNA \[qualitative\] is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority.
* Has a known history of active TB (Bacillus Tuberculosis).
* Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
* Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.

Where this trial is running

New York, New York and 2 other locations

• Weill Cornell Medicine — New York, New York, United States (Recruiting)
• Brooklyn Methodist Hospital - NewYork Presbyterian — New York, New York, United States (Recruiting)
• New York Presbyterian Hospital - Queens — New York, New York, United States (Recruiting)

Study contacts

• Principal investigator: Silvia Formenti, M.D. — Weill Cornell Medicine - New York Presbyterian Hospital
• Study coordinator: Fabiana Gregucci, M.D.

Conditions Metastatic Breast Cancer; Brain Metastases