Purpose

This study will investigate Harmonic Motion Imaging guided Focused Ultrasound (HMIgFUS) method for ablation and sonoporation monitoring of breast tumors. The aim of this study is to evaluate the efficacy of real-time guidance/monitoring and ablation/sonoporation method. The hypothesis behind this proposed study is that High Intensity Focused Ultrasound (HIFU) can be used to ablate tumor tissue, and microbubble-mediated Low Intensity Focused Ultrasound (LIFU) can be used to sonoporate tumor vasculature. The investigators of this study also hypothesize that HMI can be used to monitor HIFU ablation by measuring the changes in tissue stiffness that occur as a result of thermal ablation, guide LIFU sonoporation and HIFU ablation targeting stiff tumor tissue, and the HMI-monitored stiffness changes during ablation will correlate with post-treatment immune response. The ultimate goals of this study are: first, to assess whether these techniques can be used in the clinic in order to provide a well-monitored, noninvasive tumor ablation/sonoporation method for benign tumors and breast cancers, to minimize side effects due to invasiveness and enhance therapeutic effects of current methods; second, to make full use of the real-time monitoring capability of HMIgFUS for more precise, point-of-care treatment planning to ensure success of ablation/sonoporation and immune activation.

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
Female
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Women age 18 years or older with benign tumors or early-stage, non-metastatic breast cancer (stage I without the involvement of axillary lymph nodes) - Scheduled to receive surgical resection of the tumor by their clinical care team

Exclusion Criteria

  • Patients who have received or are scheduled to receive thermal ablation or treatment of the tumor as part of their clinical care - Pregnant or lactating - Presence of breast implants - Have a history of laser or radiation therapy to the targeted breast. Microbubble-mediated LIFU, i.e., sonoporation Inclusion criteria: - Women 18 years or older - Deemed eligible to receive neoadjuvant systemic therapy as per the treating physician, with the dose and schedule deemed appropriate by the treating physician - Any stage invasive breast cancer provided the primary breast tumor size is at least 4 mm Exclusion criteria: - Pregnant or lactating - Presence of breast implants - History of laser or radiation therapy to the affected breast - Contraindication history or hypersensitivity to ultrasound contrast agents, e.g., Definity, including polyethylene glycol (PEG) allergy.

Study Design

Phase
Phase 1
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Other
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
HMIgFUS
Each study participants' tumors will be imaged using Harmonic Motion Imaging (HMI), an ultrasound elastography method. A central portion of the tumor will then be ablated and monitored using Harmonic Motion Imaging guided Focus Ultrasound (HMIgFUS). Only one portion of the tumor will be ablated; the other portions of the tumor, including tumor margins, will not be ablated. Following ablation, the tumor will be imaged again using HMI.
  • Procedure: Harmonic motion imaging guided focused ultrasound (HMIgFUS)
    Harmonic motion imaging guided focused ultrasound (HMIgFUS) is a combined treatment and imaging method, in which focused ultrasound (FUS) is used to thermally ablate tissue and harmonic motion imaging (HMI) is used for FUS guidance and monitoring. FUS applies high intensity focused ultrasound waves at its specified target to heat the tissue over a specified duration, causing cell death at the target area. HMI is an elasticity imaging technique which induces dynamic tissue vibrations at the target for tissue elasticity characterization. One of the inclusion criteria for this study is that participants must be scheduled for surgical excision of their breast tumor. In this study, HMIgFUS will be applied to anesthetized participants immediately prior to their scheduled surgery. HMI imaging will also be performed immediately prior to and after HMIgFUS application.
Experimental
HMIgLIFU
Eligible participants have early-stage breast cancers and are scheduled to receive neoadjuvant chemotherapy as part of their clinical care. On the day of chemotherapy infusion, elasticity images of the lesions and surrounding tissues will be collected using HMI before infusion after tumor identification on ultrasound imaging. Within an hour after infusion, the participants' tumors will be treated with microbubble-mediated Low-Intensity Focused Ultrasound (LIFU), i.e. sonoporation.
  • Procedure: Microbubble-mediated Low Intensity Focused Ultrasound (LIFU)
    Microbubble-mediated Low Intensity Focused Ultrasound (LIFU) is a minimally invasive procedure which delivers localized ultrasound energy to the target region, causing cavitation of microbubbles to safely and transiently increase the permeability of vessels that aids local delivery of medicine.
    Other names:
    • Sonoporation
  • Drug: Microbubbles
    Definity is a diagnostic ultrasound enhancing agent used to improve the clarity of echocardiograms and other ultrasound images. It consists of tiny, gas-filled lipid microspheres (about the size of a red blood cell) that circulate in the bloodstream to reflect ultrasound waves.
    Other names:
    • DEFINITY
    • Perflutren Lipid Microsphere

Recruiting Locations

Columbia University Irving Medical Center/NYP
New York, New York 10032
Contact:
Shiqi Hu, MSc
917-664-5382
sh4193@columbia.edu

More Details

Status
Recruiting
Sponsor
Columbia University

Study Contact

Shiqi Hu, MSc
917-664-5382
sh4193@columbia.edu

Detailed Description

The objectives of this study are to demonstrate the initial clinical feasibility of using Harmonic Motion Imaging (HMI) for guiding and monitoring 1) Focused Ultrasound Surgery (FUS) in patients with benign tumors and stage 1 non-metastatic breast cancers and 2) microbubble-mediated Low Intensity Focused Ultrasound (LIFU), i.e., sonoporation, in early-stage, non-metastatic breast cancer patients. The secondary objective is to investigate the correlation between HMI-informed treatment response with patients' post-treatment immune profile. FUS is a non-invasive, non-ionizing treatment procedure that precisely focuses and delivers a large amount of ultrasound energy to the target area, causing a localized temperature rise and cell necrosis at the target. Patients with small solid tumors without positive lymph nodes have the highest survival rate. However, especially for patients with benign tumors (most common in younger women) and older patients (>65 years old) who fit these criteria, an alternative treatment technique that is far less invasive than the current surgical or invasive ablative intervention may be more beneficial. The main advantage of treating breast tumors with focused ultrasound ablation (FUS) is its noninvasiveness, i.e., no need for surgery. Without surgery, recovery from the procedure is much faster, patients may experience less pain, and cosmetic results may be improved. On the other hand, microbubbles have been approved for use by the FDA in contrast-enhanced ultrasound imaging, e.g., cardiac and liver imaging. Research has shown that microbubble mediated LIFU can improve intratumoral drug uptake via a phenomenon termed sonoporation, as a result of cavitation of microbubbles. Sonoporation does not cause any unexpected bias or additional toxicity compared with chemotherapy alone. Currently, sonoporation lacks imaging guidance. In this study, HMI and contrast-enhanced power Doppler will be investigated to guide and monitor sonoporation. Microbubbles will be injected at an FDA-approved dose and route. HMI is an ultrasound elasticity method that can provide measurements of the locally generated mechanical response and inherent mechanical properties of tissues. The result is a new image that contains unique localized information on the relative stiffness in and around the tumor. HMI can be performed simultaneously with HIFU ablation so that HIFU ablation can be monitored with HMI without interruption of HIFU treatment. When used for monitoring thermal ablation using FUS, the integrated system is referred to as HMIgFUS, which stands for Harmonic Motion Imaging for Focused Ultrasound. The resulting synchronous monitoring system has the ability to follow and identify the areas of necrosis. This study aims to evaluate the HMI technique for monitoring FUS ablation in a clinical setting and investigate the correlation between HMI-monitored displacement and patients' immune response.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.