Focused Ultrasound and Gemcitabine in Breast Cancer (Breast 54)

Focused Ultrasound With Low-Dose Gemcitabine to Augment Immune Control of Early Stage Breast Cancer

This study will test the use of focused ultrasound ablation, low-dose gemcitabine (a chemotherapy) and the combination of focused ultrasound ablation plus low-dose gemcitabine in patients with early-stage breast cancers. We will be testing the effects of each of these regimens on cells in the immune system. We hypothesize that the combination of focused ultrasound ablation and gemcitabine will decrease myeloid-derived suppressor cells and will increase T cell activity. We also hypothesize that focused ultrasound ablation and low-dose gemcitabine will be safe and will result in non-inferior surgical completion rates and tumor margin assessments.

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Cancer; Breast Neoplasms
• Intervention / Treatment: Device: Focused Ultrasound; Other: Gemcitabine and Focused Ultrasound

• Study Type: Interventional
• Enrollment (Estimated): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Disease Status

  • Patients must have histologically confirmed, newly diagnosed breast cancer, stage 1-3 disease and be appropriate surgical candidates for complete resection. Recurrent disease patients must have disease localized to the breast, chest wall or axilla and must be surgical candidates for completion resection of recurrent disease.
  • If genomic profiling is performed, then the results must indicate that the cancer is high-risk
  • Any receptor status may be eligible (estrogen receptor, progesterone receptor, HER2 receptor)
  • Patients must have a lesion in the breast/chest wall/axilla that is accessible to focused ultrasound ablation.

Accessible is defined as the following:

• A targetable portion of the tumor must be ≥ 5mm from the skin
• The rib cage should not be in the prefocal ultrasound path or behind the target area of the lesion (minimum distance from the posterior aspect of the target area to rib cage must be at least 10 mm).

Participants must have at least one high-risk feature of breast cancer (tumor size and nodal status may be measured by mammogram, MRI, US, CT, or calipers):

• Triple negative breast cancer with Tumor size ≥10mm
• Lymph node involvement by imaging or biopsy (any receptor status, any size)
• Tumor size ≥ 20mm (estrogen receptor positive, HER2 negative)
• Tumor size ≥ 10mm (HER2 receptor positive, any ER status)

• Tumor size ≥ 10mm and Oncotype or Mammaprint high status (estrogen receptor positive, HER2 negative) *If patient has more than one tumor, then the treated tumor must have a high-risk feature (if 2 tumors meet high risk criteria), they may both be treated).

  • Willing and able to provide written consent
  • Stated willingness to comply with all study procedures and availability for the duration of the study.
  • Male or female, ≥ 18 years
  • Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion.
  • ECOG performance status of 0-2
  • Adequate organ function
  • Agreement to adhere to lifestyle considerations throughout the study duration

Exclusion Criteria:

• Received other treatment (standard or investigational) for their current breast cancer.
• Pregnant or lactating

• Diagnosis of immunodeficiency or receiving systemic steroid therapy within 7 days prior to enrollment with the following exceptions:

  • In patients with adrenal or pituitary insufficiency replacement steroid doses are allowed; however, daily doses of 10 mg or more of prednisone (or equivalent) per day administered parenterally or orally are not allowed in patients with normal adrenal and pituitary function.
  • Inhaled steroids (e.g.: Advair®, Flovent®, Azmacort®) are permitted at low doses (less than 500 mcg fluticasone per day, or equivalent).
  • Topical, nasal, and intra-articular corticosteroids are acceptable.
• Known allergic reactions to gemcitabine
• Breast implant on the side of the body that will receive HIFU application
• Known history of HIV (Patients with HIV will be excluded because immunotherapy may impact the T cell profiling as part of the biologic correlates and the natural history of the disease)
• Known active Hepatitis B virus or Hepatitis C virus
• Other malignancy other than basal cell carcinoma of the skin or squamous cell carcinoma of the skin that is undergoing potentially curative therapy, ductal carcinoma in situ (DCIS), or in situ cervical cancer
• Active infection requiring other systemic therapy
• Participants in whom there is a medical contraindication or potential problem in complying with the requirements of the protocol in the opinion of the investigator.
• Any condition(s) or diagnosis, both physical or psychological, or physical exam finding that precludes participation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm B: FUS	Device: Focused Ultrasound; Focused ultrasound will be applied to up to 2 breast lesions on day 8.; Other Names: EchoPulse
Experimental: Arm C: GEM/FUS	Other: Gemcitabine and Focused Ultrasound; Gemcitabine (900 mg/m2) will be administered intravenously on day 1.Focused ultrasound will be applied to up to 2 breast lesions on day 8.; Other Names: Gemzar, EchoPulse

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with any ≥ grade 3 adverse event	Adverse events as measured by CTCAE v5.0	Adverse events collected through 30 days after the last study treatment
Rate of participants experiencing a delay in surgery	Rate of participants experiencing a delay in surgery, beyond day 26	Through month 7 (Follow-up visit 2)
Rate of positive margins following surgery	Number of participants who have positive tumor margins at the time of surgery	Day 22

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The effect of the treatments on myeloid-derived suppressor cells (MDSC) and CD8+ T cells in the tumor microenvironment	MDSC/CD8 ratio in the tumor	Day 22
The effect of the treatments on circulating activated T cells	Proportion of activated T cells in the blood	Measured through 30 days after the last active treatment visit
The effects of the treatments on dendritic cells in the tumor microenvironment	Dendritic cell maturation in the tumor; we will stain cells using panels of markers for maturation and use multi-spectral immunohistochemistry and/or flow cytometry to characterize the dendritic cell populations.	Day 22
Patient satisfaction with treatment regimen and surgery	Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) will be used to assess patient satisfaction with the treatment regimen and surgery; graded on a scale from 0 to 4 and scoring outcomes vary depending on the question that is being asked.	through month 7
Patient and physician reported results on cosmesis	Harvard /NSABP/RTOG Breast Cosmesis Grading Scale will be used to assess cosmesis; graded is on a scale of 1 to 4 with a higher score indicating a poorer outcome.	through month 7
Residual cancer burden	MD Anderson Residual Cancer Burden Calculator	Day 22

Collaborators and Investigators

• Sponsor: Patrick Dillon, MD
• Investigators: Principal Investigator: Patrick Dillon, MD, University of Virginia

Study record dates

Study Major Dates

• Study Start (Actual): January 27, 2022
• Primary Completion (Estimated): September 1, 2029
• Study Completion (Estimated): February 1, 2030

Study Registration Dates

• First Submitted: March 9, 2021
• First Submitted That Met QC Criteria: March 11, 2021
• First Posted (Actual): March 12, 2021

Study Record Updates

• Last Update Posted (Actual): June 16, 2026
• Last Update Submitted That Met QC Criteria: June 12, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Gemcitabine
• Other Study ID Numbers: 200277

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No