Recruiting

Phase 1

Phase 2

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

Sponsor:

Weill Medical College of Cornell University

Code:

NCT03449238

Conditions

Metastatic Breast Cancer

Brain Metastases

Eligibility Criteria

Sex: Female

Age: 19 - 70+

Healthy Volunteers: Not accepted

Interventions

Pembrolizumab

Study Details

Brief summary:

Patients with metastatic breast cancer with at least 2 brain metastases will receive pembrolizumab every 3 weeks. Patients will undergo stereotactic radiosurgery (SRS) to one of the brain lesions. Pembrolizumab infusion will be given on Day 4 (+/-1) after SRS treatment at the standard dose of 200mg IV over 30 minutes and repeated every 3 weeks until disease progression or unacceptable toxicity.

Conditions

Metastatic Breast Cancer

Brain Metastases

Study ID

NCT03449238

Start date

Nov 15, 2018

Status verified date

Mar, 2026

Completion date

Dec 31, 2030

Anticipated

Primary completion date

Dec 31, 2028

Anticipated

Eligibility Criteria

Sex: Female

Age: 19 - 70+

Healthy Volunteers: Not accepted

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.

Study Design

Enrollment

41 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

other: Pembrolizumab and SRS

Pembrolizumab infusion will be given on Day 4 (+/-1) after SRS treatment at the standard dose of 200mg IV over 30 minutes and repeated every 3 weeks until disease progression or unacceptable toxicity.

Interventions

Pembrolizumab

Primary outcome measure

Tumor response for non-irradiated brain lesions at 8 weeks according to RECIST1.1 [ Time Frame: 8 weeks ]
Correlation of abscopal responses with the radiation dose received [ Time Frame: 1 year ]
Overall survival - assessed from the start of study drug until death in non-irradiation metastases in the rest of the body by routine imaging. [ Time Frame: 3 years ]

Central Contacts and Locations

Central contacts

Fabiana Gregucci, M.D.

646-962-3110 fgr4002@med.cornell.edu

Locations

Weill Cornell Medicine

Recruiting

New York, New York, United States, 10065

Contacts

Fabiana Gregucci, M.D.

646-962-3110 fgr4002@med.cornell.edu

Brooklyn Methodist Hospital - NewYork Presbyterian

Recruiting

New York, New York, United States, 11215

Contacts

Izael Nino, M.S.

929-470-9426 izn4001@med.cornell.edu

Principal Investigator:

Hani Ashamalla, M.D.

New York Presbyterian Hospital - Queens

Recruiting

New York, New York, United States, 11355

Contacts

Krystalle Lyons, B.S.

krl4003@med.cornell.edu

Principal Investigator:

Andrew Brandmaier, M.D.

More Information

Sponsor

Weill Medical College of Cornell University

Last update posted

Mar 30, 2026

Last verified

Mar, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Weill Medical College of Cornell University on 2026-03-30.