Clinical trial NCT04796220: Focused Ultrasound and Gemcitabine in Breast Cancer
Official title: Focused Ultrasound With Low-Dose Gemcitabine to Augment Immune Control of Early Stage Breast Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Breast Cancer
Breast Neoplasms
Lead sponsor: University of Virginia
Sponsor class: OTHER
First posted: 2021-03-12
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of participants with any ≥ grade 3 adverse event
timeFrame: Adverse events collected through 30 days after the last study treatment
measure: Rate of participants experiencing a delay in surgery
timeFrame: Through month 7 (Follow-up visit 2)
measure: Rate of positive margins following surgery
timeFrame: Day 22
Secondary outcomes:
measure: The effect of the treatments on myeloid-derived suppressor cells (MDSC) and CD8+ T cells in the tumor microenvironment
timeFrame: Day 22
measure: The effect of the treatments on circulating activated T cells
timeFrame: Measured through 30 days after the last active treatment visit
measure: The effects of the treatments on dendritic cells in the tumor microenvironment
timeFrame: Day 22
measure: Patient satisfaction with treatment regimen and surgery
timeFrame: through month 7
measure: Patient and physician reported results on cosmesis
timeFrame: through month 7
measure: Residual cancer burden
timeFrame: Day 22
Other outcomes:
Locations:
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
Study officials:
affiliation: University of Virginia
name: Patrick Dillon, MD
role: PRINCIPAL_INVESTIGATOR
References: