Breast CancerPhase 1Breast-48NCT03237572
Focused Ultrasound and Pembrolizumab in Metastatic Breast Cancer
A Phase 1 study testing Pembrolizumab and High-intensity focused ultrasound (HIFU) in people with Breast Cancer, run by Patrick Dillon, MD at 1 site in United States.
Trial summary
This pilot study evaluates the use of high-intensity focused ultrasound (HIFU) combined with pembrolizumab in patients with metastatic breast cancer. One-half of participants will be randomized to receive the first dose of pembrolizumab after HIFU and one-half of participants will be randomized to receive their first… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Pembrolizumab and High-intensity focused ultrasound (HIFU)
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Sep 2017to 17 Jun 2022
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed metastatic or unresectable breast cancer
- Any receptor status (estrogen receptor, progesterone receptor, HER2 receptor). Patients who are HR+ should also no longer be candidates for hormonal-based therapy. Patients who are HER2+ should have progressed on or no longer be candidates for available HER2 directed therapy. Hormonal therapy must be stopped prior to day 1 of treatment.
- Patients must have had at least one prior line of therapy for breast cancer in the metastatic setting.
- Patients must have an accessible lesion in the breast/chest wall/axilla which has not been previously thermally ablated. Prior breast irradiation is acceptable if the lesion has recurred or grown following radiation.
- Patients must agree to use an adequate method of contraception for the course of the study through 120 days after the last dose of study medication.
- Patients must have at least one target lesion in breast/chest wall/axilla which is amenable to application of high intensity focused ultrasound:
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- Patients must be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion.
- Performance status of 0 or 1 on the ECOG Performance Scale.
- Adequate organ function
Who cannot join
- Patients currently participating and receiving study therapy or patients who have participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
- Patients with a diagnosis of immunodeficiency, patients receiving systemic steroid therapy or, patients who have received any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
- Patients with a known history of active Tuberculosis
- Hypersensitivity to pembrolizumab or any of its excipients
- Prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1. Patients who have not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier are excluded.
- Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1. Patients who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
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- Known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
- Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
- Active autoimmune disease that has required systemic treatment in the past 2 years.
- History of (non-infectious) pneumonitis that required steroids or current pneumonitis.
- Active infection requiring systemic therapy.
- Pregnancy
- Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent within the prior 24 weeks.
- Known history of Human Immunodeficiency Virus (HIV)
- Receipt of a live vaccine within 30 days of planned start of study therapy.
- HIFU must not be applied to a breast with an implant. A region outside of the breast may be targeted as long as the targeted area is at least 10mm away from an implant.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Virginia
Charlottesville, Virginia, 22908
About this study
Official title: Focused Ultrasound Therapy to Augment Antigen Presentation and Immune-Specificity of Checkpoint Inhibitor Therapy With Pembrolizumab in Metastatic Breast Cancer
This pilot study evaluates the use of high-intensity focused ultrasound (HIFU) combined with pembrolizumab in patients with metastatic breast cancer. One-half of participants will be randomized to receive the first dose of pembrolizumab after HIFU and one-half of participants will be randomized to receive their first dose of pembrolizumab before HIFU.
- Conditions
- Breast Cancer
- Being tested
- Pembrolizumab, High-intensity focused ultrasound (HIFU)
- Keywords
- breast cancer, pembrolizumab, focused ultrasound, immunotherapy
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
Also called Keytruda
Pembrolizumab (200 mg)
High-intensity focused ultrasound (HIFU)Device
Ablation will target 50% of the tumor, up to 3 cubic centimeters
| Study group | Role | What they receive |
|---|---|---|
| Arm A: 1st dose of pembrolizumab after HIFU | Experimental | Pembrolizumab (200 mg) administered intravenously, days 22, 43, 64, followed by day 1 of each ensuing 3 -week cycle. Focused ultrasound tumor ablation day 15. High-intensity focused ultrasound ablation will target 50% of the tumor, up to 3 cubic centimeters. Receives: Drug: Pembrolizumab; Device: High-intensity focused ultrasound (HIFU) |
| Arm B: 1st dose of pembrolizumab before HIFU | Experimental | Pembrolizumab (200 mg) intravenously, days 1, 22, 43, 64, followed by day 1 of each ensuing 3 -week cycle. Focused ultrasound tumor ablation day 15. High-intensity focused ultrasound ablation will target 50% of the tumor, up to 3 cubic centimeters. Receives: Drug: Pembrolizumab; Device: High-intensity focused ultrasound (HIFU) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Proportion of CD8+ Tumor Infiltrating Lymphocytes
How many of the immune cells inside a tumor are a specific type of "killer" T cell
Measured: baseline and week 4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Aug 2017
- Study start25 Sep 2017
- Primary completion1 Jun 2022
- Study completion17 Jun 2022
Why it stopped: Low rate of enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Pilot, 2-arm randomized study
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Patrick Dillon, MD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Patrick Dillon, MD, University of Virginia
- Investigators
- Patrick Dillon, MD, Principal investigator, University of Virginia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03237572
- Sponsor's protocol ID
- 19900
- Acronym
- Breast-48
- Status last verified
- Jan 2026
- First submitted
- 31 Jul 2017
- Last updated
- 9 Feb 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
Publications
Sheybani ND, Witter AR, Thim EA, Yagita H, Bullock TNJ, Price RJ. Combination of thermally ablative focused ultrasound with gemcitabine controls breast cancer via adaptive immunity. J Immunother Cancer. 2020 Aug;8(2):e001008. doi: 10.1136/jitc-2020-001008.
PubMed 32819975
Study at a glance
From the registry record, last updated by the sponsor on 9 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Focused Ultrasound Therapy to Augment Antigen Presentation and Immune-Specificity of Checkpoint Inhibitor Therapy With Pembrolizumab in Metastatic Breast Cancer
- ClinicalTrials.gov ID
- NCT03237572
- Acronym / sponsor ID
- Breast-48 / 19900
- Conditions
- Breast Cancer
- Keywords
- breast cancer, pembrolizumab, focused ultrasound, immunotherapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low rate of enrollment
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Patrick Dillon, MDUniversity, hospital or other
- Study start
- 25 Sep 2017 (actual)
- Primary completion
- 1 Jun 2022 (actual)
- Study completion
- 17 Jun 2022 (actual)
- First posted
- 2 Aug 2017 (actual)
- Results
- Posted 9 Feb 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This pilot study evaluates the use of high-intensity focused ultrasound (HIFU) combined with pembrolizumab in patients with metastatic breast cancer. One-half of participants will be randomized to receive the first dose of pembrolizumab after HIFU and one-half of participants will be randomized to receive their first dose of pembrolizumab before HIFU.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Pilot, 2-arm randomized study
| Arm | Type | Receives |
|---|---|---|
| Arm A: 1st dose of pembrolizumab after HIFU | Experimental | Drug: Pembrolizumab, Device: High-intensity focused ultrasound (HIFU)Pembrolizumab (200 mg) administered intravenously, days 22, 43, 64, followed by day 1 of each ensuing 3 -week cycle. Focused ultrasound tumor ablation day 15. High-intensity focused ultrasound ablation will target 50% of the tumor, up to 3 cubic centimeters. |
| Arm B: 1st dose of pembrolizumab before HIFU | Experimental | Drug: Pembrolizumab, Device: High-intensity focused ultrasound (HIFU)Pembrolizumab (200 mg) intravenously, days 1, 22, 43, 64, followed by day 1 of each ensuing 3 -week cycle. Focused ultrasound tumor ablation day 15. High-intensity focused ultrasound ablation will target 50% of the tumor, up to 3 cubic centimeters. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Histologically confirmed metastatic or unresectable breast cancer
- Any receptor status (estrogen receptor, progesterone receptor, HER2 receptor). Patients who are HR+ should also no longer be candidates for hormonal-based therapy. Patients who are HER2+ should have progressed on or no longer be candidates for available HER2 directed therapy. Hormonal therapy must be stopped prior to day 1 of treatment.
- Patients must have had at least one prior line of therapy for breast cancer in the metastatic setting.
- Patients must have an accessible lesion in the breast/chest wall/axilla which has not been previously thermally ablated. Prior breast irradiation is acceptable if the lesion has recurred or grown following radiation.
- Patients must agree to use an adequate method of contraception for the course of the study through 120 days after the last dose of study medication.
Key exclusion criteria (16 listed)
- Patients currently participating and receiving study therapy or patients who have participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
- Patients with a diagnosis of immunodeficiency, patients receiving systemic steroid therapy or, patients who have received any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
- Patients with a known history of active Tuberculosis
- Hypersensitivity to pembrolizumab or any of its excipients
- Prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1. Patients who have not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier are excluded.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PembrolizumabAlso: KeytrudaPembrolizumab (200 mg) | Drug | Arm A: 1st dose of pembrolizumab after HIFU, Arm B: 1st dose of pembrolizumab before HIFU |
| High-intensity focused ultrasound (HIFU)Ablation will target 50% of the tumor, up to 3 cubic centimeters | Device | Arm A: 1st dose of pembrolizumab after HIFU, Arm B: 1st dose of pembrolizumab before HIFU |
Primary outcome
Change in Proportion of CD8+ Tumor Infiltrating Lymphocytes
Time frame: baseline and week 4
How many of the immune cells inside a tumor are a specific type of "killer" T cell
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Feb 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32819975Sheybani ND, Witter AR, Thim EA, Yagita H, Bullock TNJ, Price RJ. Combination of thermally ablative focused ultrasound with gemcitabine controls breast cancer via adaptive immunity. J Immunother Cancer. 2020 Aug;8(2):e001008. doi: 10.1136/jitc-2020-001008.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Patrick Dillon, MD principal investigator
University of Virginia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Pembrolizumab and High-intensity focused ultrasound (HIFU) in people with Breast Cancer, run by Patrick Dillon, MD at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 9 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Feb 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Proportion of CD8+ Tumor Infiltrating Lymphocytes (time frame: baseline and week 4). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03237572, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Feb 2026.