Novel MRI-Guided Ultrasound Stimulated Microbubble Radiation Treatment for Patients With Chest-wall and Breast Cancer (USmBRT-B)

December 7, 2023 updated by: Dr. Gregory Czarnota, Sunnybrook Health Sciences Centre

Novel Magnetic Resonance Imaging -Guided Ultrasound-Stimulated Microbubble Radiation Treatment for Patients With Chest-Wall and Locally Advanced Breast Cancer

The objective of this study is to demonstrate the feasibility of novel MRI-guided ultrasound stimulated microbubble treatment to enhance radiation effects in humans receiving external beam radiotherapy delivered using a LINAC (linear accelerator) radiation therapy device.

Study Overview

Status

Completed

Conditions

Detailed Description

The objective of this study is to demonstrate the feasibility of novel MRI-guided ultrasound stimulated microbubble treatment to enhance radiation effects in humans receiving external beam radiotherapy delivered using a LINAC (linear accelerator) radiation therapy device. The investigators have previously demonstrated that ultrasound and microbubble mediated endothelial cell perturbation can significantly enhance the effectiveness of radiation. It enhances tumour response to radiation significantly by synergistically destroying tumour blood vessels. The technique is targeted spatially and achieves tumour specificity by confining the low-power ultrasonic fields that stimulate microbubbles to the tumour location only. By perturbing the tumour vasculature and activating specific genetic pathways, the technique sensitizes the targeted tissues to the subsequent therapeutic application of radiation, resulting in significantly enhanced cell killing. The primary aim of this research is to evaluate the safety profile of MRI-guided ultrasound stimulated microbubble treatment and radiation in patients with chest wall and breast cancer. The secondary aim is to evaluate tumor (primary and/or nodal) response to MRg-FU + MB and radiation, as measured radiologically within the treated therapeutic regions.

Study Type

Interventional

Enrollment (Actual)

20

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

    • Ontario
      • Toronto, Ontario, Canada, M4N 3M5
        • Sunnybrook Health Sciences Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age ≥ 18 years
  • All biopsy-confirmed invasive ductal, invasive lobular and other rare histologic types of carcinoma
  • Patients with early stage Breast cancer, or LABC ; i.e., Stage IIA - IIIC cancers (T2 N0 M0 to Any T, N3, M0) or Stage IV (Any T, Any N, M1) per AJCC guidelines (8th Edition)
  • Assessed by a multidisciplinary team of treating medical, surgical and radiation oncologist and found suitable for the treatment
  • Patient referred for palliative radiotherapy or standard radiotherapy, which may include any of the following dose regimens: 1) 20 Gy in 5 fractions, 2) 30 Gy in 10 fractions, 3) 40 Gy in 10 fractions, 4) 50 Gy in 20 fractions, 5) 60 Gy in 30 fractions and 6) 66 Gy in 33 fractions.
  • Able to understand and give informed consent
  • Weight < 140 kg
  • Target lesion accessible for MRg-FU+MB procedure
  • Able to communicate sensation during the procedure
  • Creatinine within normal institutional limits or creatinine clearance >60 mL/min/1.73 m2 for patients with creatinine levels above institutional upper limit of normal.

Exclusion Criteria:

  • Pregnant or lactating women may not participate due to the embryotoxic effects of protocol treatment. Women/ men of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.
  • Unable to have a contrast-enhanced MRI scan - standard of care criteria
  • Patients on anthracycline or taxane based chemotherapy
  • Patients with metallic or breast implants
  • Subjects with inflammatory breast cancer, connective tissue disorder, musculoskeletal deformity
  • Target lesion causing ulceration, bleeding or discharge of the overlying skin
  • A fibrotic scar along the proposed FU beam path
  • Severe cardiovascular, neurological, renal or hematological chronic disease
  • Eastern Cooperative Oncology Group (ECOG) Performance Status ≥ 3
  • Any condition in the investigator's opinion precludes participation
  • Bleeding disorders/ High risk for deep vein thrombosis
  • Unable to tolerate required stationary position during treatment
  • Allergic to Definity microbubbles
  • Cardiac disease or unstable hemodynamics including myocardial infarction within six months, unstable angina, congestive heart failure, ejection fraction < 50%, cardiac shunts, cardiac arrythmia and cardiac pacemaker.
  • Contraindication to perflutren including subjects with a family or personal history of QT prolongation or taking concomitant medications known to cause QTc prolongation like cisapride, erythromycin, tricyclic antidepressants, Class IA and III antiarrhythmic agents and some antipsychotics like haloperidol, droperidol, quetiapine, thioridazine, ziprasidone.
  • QT prolongation observed on screening ECG (QTc > 450ms for men or >470ms for women)
  • Severe hypertension (diastolic BP > 100 mmHg)
  • History of bleeding disorder, coagulopathy
  • Severely impaired renal function with estimated glomerular filtration rate < 30ml/min/1.73m2 and/or on dialysis

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: MRg-FUS MB Treatment
Patients with locally advanced breast cancer (LABC) and chest wall tumours will receive MRI-guided ultrasound-stimulated microbubble-treatment combined with radiotherapy on a LINAC.
MRI-guided ultrasound-stimulated microbubble-treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of toxicity and adverse events using MRg-FUS+MB treatment in patients with chest-wall and locally advanced breast cancer
Time Frame: 90 days
Incidence of toxicity and adverse events
90 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Radiological Response
Time Frame: 90 days
The secondary endpoint is radiological response in breast cancer following MRg-FU + MB + radiation, after a 3 month follow up.
90 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Dr. Gregory Czarnota, MD, Sunnybrook Health Sciences Centre

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 22, 2020

Primary Completion (Actual)

June 21, 2023

Study Completion (Actual)

June 21, 2023

Study Registration Dates

First Submitted

June 11, 2020

First Submitted That Met QC Criteria

June 11, 2020

First Posted (Actual)

June 16, 2020

Study Record Updates

Last Update Posted (Actual)

December 13, 2023

Last Update Submitted That Met QC Criteria

December 7, 2023

Last Verified

December 1, 2023

More Information

Terms related to this study

Other Study ID Numbers

  • 077-2019

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Breast Cancer

Clinical Trials on Definity Suspension for Injection

3
Subscribe