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

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

The objective of this study is to demonstrate the efficacy and response of novel Magnetic Resonance Imaging (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: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Definity; Device: Sonalleve Focused Ultrasound Device

Detailed Description

The approach uses relatively low-power ultrasound, operating with lower power levels than high intensity focused ultrasound and ultrasound-based hyperthermia techniques, delivered on the Sonalleve platform. The tumour will be sonicated before the radiation to enhance the effect of therapy. The technique is spatially targeted and stimulates microbubbles using low-power ultrasonic fields in the tumour location only. The primary aim is to evaluate tumour response to MRg-FUS + MB and radiation, as measured radiologically or clinically within the treated therapeutic target regions.The secondary aim of this research is to evaluate early and late effect profiles of MRI- guided ultrasound stimulated microbubble treatment and radiation in patients with inoperable breast/chest wall tumours or LABC at 1 day, 1 week, 2 weeks, 1 month, 3 months, 6 months and 1 year after treatment.

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Dr.Gregory Czarnota, MD, Ph.D.; Phone Number: 7073 +1 (416) 480-6128; Email: Gregory.Czarnota@sunnybrook.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4N 3M5
      • Recruiting
      • Sunnybrook Health Sciences Centre
      • Contact: Dr. Gregory Czarnota, PhD, MD; Phone Number: (416) 480-6128; Email: gerogory.czarnota@sunnybrook.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 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 as indicated, by a multidisciplinary team of treating medical, surgical and radiation oncologist and found suitable for radiation treatment.
• Patient referred for standard palliative radiotherapy or curative radiotherapy, which may include (but are not limited to) any of the following dose regimens: 1) 5-8 Gy in one fraction, 2) 20 Gy in 5 fractions, 3) 30 Gy in 5 fractions, 4) 35 Gy in 5 fractions, 5) 30 Gy in 10 fractions, 6) 40 Gy in 10 fractions, 5) 50 Gy in 20 fractions, 6) 60 Gy in 30 fractions and 7) 66 Gy in 33 fractions, or radiobiologically similar doses.
• Able to understand and give informed consent.
• Weight < 140 kg.
• Target lesion accessible for MRg-FUS+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.
• Unable to have a contrast-enhanced MRI scan - standard of care criteria.
• Patients having received anthracycline or taxane based chemotherapy within the past 5 days.
• Patients intended for surgical management of the target tumour.
• Patients with metallic or breast implants.
• Subjects with connective tissue disorder, musculoskeletal deformity.
• Target lesion causing deep ulceration, bleeding or discharge of the overlying skin.
• A fibrotic scar along the proposed FUS beam path.
• Severe cardiovascular, neurological, renal or hematological chronic disease.
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≥ 3.
• Any condition that in the investigator's opinion precludes participation.
• Unable to tolerate required stationary position during treatment.
• Allergy to Definity microbubbles.
• Cardiac disease or unstable hemodynamics including myocardial infarction within six months, unstable angina, congestive heart failure, cardiac shunts, cardiac arrhythmia 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.
• Known QT prolongation = (QTc > 450ms for men or >470ms for women) with cardiac impairment if ECG is requested as per SOC.
• History of bleeding disorder, coagulopathy.
• Severely impaired renal function with estimated glomerular filtration rate < 30ml/min/1.73m2 and/or on dialysis.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental: Treatment Arm; All biopsy confirmed breast cancer patients undergoing MRI-guided ultrasound-stimulated microbubble treatment plus radiation therapy	Drug: Definity; Stimulation of Definity microbubbles using Sonalleve device within tumour vasculature; Other Names: Microbubbles; Device: Sonalleve Focused Ultrasound Device; Sonalleve Focused Ultrasound Device

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Outcomes/Endpoint	The primary endpoint is complete response (RECIST 1.1 Criteria) in chest-wall tumours and LABC following MRg-FUS + MB + radiation after a 3 month follow up. Patients will be followed clinically thereafter as part of standard of care.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary Outcomes/Endpoint(s)	The secondary endpoint will be late effect-reported outcomes (at 1 day, 1 week, 2 weeks, 1 month, 3 months, 6 months and 1 year after treatment. A toxicity questionnaire will be used as an outcome measure.	1 year

Collaborators and Investigators

• Sponsor: Sunnybrook Health Sciences Centre
• Collaborators: Terry Fox Research Institute
• Investigators: Principal Investigator: Dr. Gregory Czarnota, MD, Ph.D., Sunnybrook Health Sciences Centre

Study record dates

Study Major Dates

• Study Start (Actual): July 25, 2024
• Primary Completion (Estimated): February 1, 2026
• Study Completion (Estimated): February 1, 2029

Study Registration Dates

• First Submitted: December 15, 2023
• First Submitted That Met QC Criteria: December 15, 2023
• First Posted (Actual): December 29, 2023

Study Record Updates

• Last Update Posted (Actual): September 27, 2024
• Last Update Submitted That Met QC Criteria: September 26, 2024
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Breast Cancer; Microbubbles; Focused Ultrasound
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: 5768

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.: No