Focused Ultrasound and Gemcitabine in Breast Cancer

Study Overview
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Brief Summary
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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.

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

Conditions
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Breast Cancer, Breast Neoplasms

Intervention / Treatment
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* Drug: Gemcitabine
* Device: Focused Ultrasound
* Other: Gemcitabine and Focused Ultrasound


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 |