Focused Ultrasound and Pembrolizumab in Metastatic Breast Cancer

NCT03237572 | Terminated Phase 1 Results DMC FDA Drug FDA Device

• 1 other identifier: 19900
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief 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 dose of pembrolizumab before HIFU.

Conditions

Breast Cancer

Keywords

breast cancer; pembrolizumab; focused ultrasound; immunotherapy

Outcome Measures

Primary Outcomes (1)

• 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

  baseline and week 4

Study Arms (2)

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.

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.

Drug: Pembrolizumab; Device: High-intensity focused ultrasound (HIFU)

Interventions

Pembrolizumab DRUG

Pembrolizumab (200 mg)

Also known as: Keytruda

Arm A: 1st dose of pembrolizumab after HIFU; Arm B: 1st dose of pembrolizumab before HIFU

High-intensity focused ultrasound (HIFU) DEVICE

Ablation will target 50% of the tumor, up to 3 cubic centimeters

Arm A: 1st dose of pembrolizumab after HIFU; Arm B: 1st dose of pembrolizumab before HIFU

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Patrick Dillon, MD: lead

Study Sites (1)

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

Related Publications (1)

• 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.

  PMID: 32819975 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Limitations and Caveats

The study terminated early due to difficulty with enrollment.

Results Point of Contact

• Title: Patrick Dillon MD
• Organization: University of Virginia

pmd5b@uvahealth.org

434-924-8073

Study Officials

• Patrick Dillon, MD

  University of Virginia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Model Details: Pilot, 2-arm randomized study

Study Record Dates

• First Submitted: July 31, 2017
• First Posted: August 2, 2017
• Study Start: September 25, 2017
• Primary Completion: June 1, 2022
• Study Completion: June 17, 2022
• Last Updated: February 9, 2026
• Results First Posted: February 9, 2026

Record last verified: 2026-01

Locations

US (1)