Focused Ultrasound and Gemcitabine in Breast Cancer

Breast Cancer Clinical Trial

— Breast 54  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04796220
• Other study ID #: 200277
• Status: Recruiting
• Phase: Phase 1
• Start date: January 27, 2022
• Est. completion date: January 2026

Study information

• Verified date: April 2024
• Source: University of Virginia
• Contact: Olena Glushakova, MS
• Phone: 434-409-6206
• Email: oyg2n[@]hscmail.mcc.virginia.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 48
• Est. completion date: January 2026
• Est. primary completion date: August 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Disease Status
• Patients must have histologically confirmed, newly diagnosed breast cancer, stage 1-3
• 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.
• 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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Gemcitabine
Gemcitabine (900 mg/m2) will be administered intravenously on day 1.

Device:
• Focused Ultrasound
Focused ultrasound will be applied to up to 2 breast lesions on day 8.

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.

Locations

Country	Name	City	State
United States	University of Virginia	Charlottesville	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
Patrick Dillon, MD

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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)
Primary	Rate of positive margins following surgery	Number of participants who have positive tumor margins at the time of surgery	Day 22
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Residual cancer burden	MD Anderson Residual Cancer Burden Calculator	Day 22