Breast 54: Focused Ultrasound and Gemcitabine in Breast Cancer

Sponsor
Patrick Dillon, MD (Other)
Overall Status
Recruiting
CT.gov ID
NCT04796220
Collaborator
(none)
48
1
3
35.2
1.4

Study Details

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Gemcitabine
  • Device: Focused Ultrasound
  • Other: Gemcitabine and Focused Ultrasound
Phase 1

Study Design

Study Type:
Interventional
Anticipated Enrollment :
48 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Focused Ultrasound With Low-Dose Gemcitabine to Augment Immune Control of Early Stage Breast Cancer
Actual Study Start Date :
Jan 27, 2022
Anticipated Primary Completion Date :
Aug 1, 2024
Anticipated Study Completion Date :
Jan 1, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: Arm A: GEM

Drug: Gemcitabine
Gemcitabine (900 mg/m2) will be administered intravenously on day 1.
Other Names:
  • Gemzar
  • 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
  • Outcome Measures

    Primary Outcome Measures

    1. Number of participants with any ≥ grade 3 adverse event [Adverse events collected through 30 days after the last study treatment]

      Adverse events as measured by CTCAE v5.0

    2. Rate of participants experiencing a delay in surgery [Through month 7 (Follow-up visit 2)]

      Rate of participants experiencing a delay in surgery, beyond day 26

    3. Rate of positive margins following surgery [Day 22]

      Number of participants who have positive tumor margins at the time of surgery

    Secondary Outcome Measures

    1. The effect of the treatments on myeloid-derived suppressor cells (MDSC) and CD8+ T cells in the tumor microenvironment [Day 22]

      MDSC/CD8 ratio in the tumor

    2. The effect of the treatments on circulating activated T cells [Measured through 30 days after the last active treatment visit]

      Proportion of activated T cells in the blood

    3. The effects of the treatments on dendritic cells in the tumor microenvironment [Day 22]

      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.

    4. Patient satisfaction with treatment regimen and surgery [through month 7]

      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.

    5. Patient and physician reported results on cosmesis [through month 7]

      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.

    6. Residual cancer burden [Day 22]

      MD Anderson Residual Cancer Burden Calculator

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Virginia Charlottesville Virginia United States 22903

    Sponsors and Collaborators

    • Patrick Dillon, MD

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Patrick Dillon, MD, Associate Professor, Department of Medicine, University of Virginia
    ClinicalTrials.gov Identifier:
    NCT04796220
    Other Study ID Numbers:
    • 200277
    First Posted:
    Mar 12, 2021
    Last Update Posted:
    May 18, 2022
    Last Verified:
    May 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    Yes
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of May 18, 2022