Focused Ultrasound and Gemcitabine in Breast Cancer (Breast 54)
Primary Purpose
Breast Cancer, Breast Neoplasms
Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Gemcitabine
Focused Ultrasound
Gemcitabine and Focused Ultrasound
Sponsored by
About this trial
This is an interventional treatment trial for Breast Cancer
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
Sites / Locations
- University of VirginiaRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Arm A: GEM
Arm B: FUS
Arm C: GEM/FUS
Arm Description
Outcomes
Primary Outcome Measures
Number of participants with any ≥ grade 3 adverse event
Adverse events as measured by CTCAE v5.0
Rate of participants experiencing a delay in surgery
Rate of participants experiencing a delay in surgery, beyond day 26
Rate of positive margins following surgery
Number of participants who have positive tumor margins at the time of surgery
Secondary Outcome Measures
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
The effect of the treatments on circulating activated T cells
Proportion of activated T cells in the blood
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.
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.
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.
Residual cancer burden
MD Anderson Residual Cancer Burden Calculator
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04796220
Brief Title
Focused Ultrasound and Gemcitabine in Breast Cancer
Acronym
Breast 54
Official Title
Focused Ultrasound With Low-Dose Gemcitabine to Augment Immune Control of Early Stage Breast Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 27, 2022 (Actual)
Primary Completion Date
August 2024 (Anticipated)
Study Completion Date
January 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Patrick Dillon, MD
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
Yes
Device Product Not Approved or Cleared by U.S. FDA
Yes
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer, Breast Neoplasms
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
48 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Arm A: GEM
Arm Type
Experimental
Arm Title
Arm B: FUS
Arm Type
Experimental
Arm Title
Arm C: GEM/FUS
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Gemcitabine
Other Intervention Name(s)
Gemzar
Intervention Description
Gemcitabine (900 mg/m2) will be administered intravenously on day 1.
Intervention Type
Device
Intervention Name(s)
Focused Ultrasound
Other Intervention Name(s)
EchoPulse
Intervention Description
Focused ultrasound will be applied to up to 2 breast lesions on day 8.
Intervention Type
Other
Intervention Name(s)
Gemcitabine and Focused Ultrasound
Other Intervention Name(s)
Gemzar, EchoPulse
Intervention Description
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.
Primary Outcome Measure Information:
Title
Number of participants with any ≥ grade 3 adverse event
Description
Adverse events as measured by CTCAE v5.0
Time Frame
Adverse events collected through 30 days after the last study treatment
Title
Rate of participants experiencing a delay in surgery
Description
Rate of participants experiencing a delay in surgery, beyond day 26
Time Frame
Through month 7 (Follow-up visit 2)
Title
Rate of positive margins following surgery
Description
Number of participants who have positive tumor margins at the time of surgery
Time Frame
Day 22
Secondary Outcome Measure Information:
Title
The effect of the treatments on myeloid-derived suppressor cells (MDSC) and CD8+ T cells in the tumor microenvironment
Description
MDSC/CD8 ratio in the tumor
Time Frame
Day 22
Title
The effect of the treatments on circulating activated T cells
Description
Proportion of activated T cells in the blood
Time Frame
Measured through 30 days after the last active treatment visit
Title
The effects of the treatments on dendritic cells in the tumor microenvironment
Description
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.
Time Frame
Day 22
Title
Patient satisfaction with treatment regimen and surgery
Description
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.
Time Frame
through month 7
Title
Patient and physician reported results on cosmesis
Description
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.
Time Frame
through month 7
Title
Residual cancer burden
Description
MD Anderson Residual Cancer Burden Calculator
Time Frame
Day 22
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Olena Glushakova, MS
Phone
434-409-6206
Email
oyg2n@hscmail.mcc.virginia.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Patrick Dillon, MD
Organizational Affiliation
University of Virginia
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Virginia
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22903
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Olena Glushakova
Phone
434-409-6206
Email
mailto:OYG2N@hscmail.mcc.virginia.edu
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Focused Ultrasound and Gemcitabine in Breast Cancer
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