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

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06185972
• Other study ID #: 5768
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: February 1, 2024
• Est. completion date: February 1, 2029

Study information

• Verified date: December 2023
• Source: Sunnybrook Health Sciences Centre
• Contact: Dr.Gregory Czarnota, MD, Ph.D.
• Phone: +1 (416) 480-6128
• Email: Gregory.Czarnota[@]sunnybrook.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 200
• Est. completion date: February 1, 2029
• Est. primary completion date: February 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Definity
Stimulation of Definity microbubbles using Sonalleve device within tumour vasculature

Device:
• Sonalleve Focused Ultrasound Device
Sonalleve Focused Ultrasound Device

Locations

Country	Name	City	State
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
Sunnybrook Health Sciences Centre	Terry Fox Research Institute

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Primary Outcomes/Endpoint	The primary endpoint is complete response 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.	2 years
Secondary	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 (see 8.9).	2 years