Clinical trial NCT06633601: MRI-Guided Ultrasound Stimulated Microbubbles Radiation Treatment for Patients with Chest-Wall and Locally Advanced Breast Cancer
Official title: A Prospective, Single-Centre, Single-Arm, Non-Randomized, Phase-I, MRI-Guided Ultrasound Stimulated Microbubbles Radiation Treatment for Patients with Chest-Wall and Locally Advanced Breast Cancer - a Pilot Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Breast Cancer
Keywords: Focused Ultrasound
Breast Cancer
Microbubbles
Lead sponsor: Sunnybrook Health Sciences Centre
Sponsor class: OTHER
Collaborators: name: Terry Fox Research Institute
First posted: 2024-10-09
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Experimental Arm
Primary purpose: TREATMENT

Brief summary: The objective of this study is to demonstrate the feasibility 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.

Detailed description: This is a prospective, single-centre, single-arm, non-randomized phase one (Phase I) clinical trial. In this study, locally advanced breast cancer (LABC) and breast/chest wall tumours not managed by surgery, patients will receive MRI-guided ultrasound-stimulated microbubble-treatment using an Arrayus MRI-FUS System combined with radiotherapy on a LINAC. Patients will lie on the MRI table with an in-built focused ultrasound platform where the tumour is kept in close contact with the transducer of the ultrasound. After exposure to the tumour with focused ultrasound, the patient will receive a standard of care LINAC-based radiation therapy.

Eligibility criteria: 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 \>60mL/min/ Novel MRI-Guided Ultrasound Stimulated Microbubble Radiation Treatment for Patients with Chest-Wall and Locally Advanced Breast Cancer. 1.73m2 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 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.

Primary outcomes:
measure: Safety profile of MRI- guided ultrasound stimulated microbubble treatment and radiation in patients with inoperable breast/chest wall tumours or LABC.
timeFrame: 2 years
Secondary outcomes:
measure: Tumour size response to MRg-FUS + MB and radiation, as measured radiologically or clinically within the treated therapeutic regions.
timeFrame: 2 years
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
Study officials:
affiliation: Sunnybrook Health Sciences Centre
name: Gregory Czarnota, MD, PhD.
role: PRINCIPAL_INVESTIGATOR
References: