MRI-guided ultrasound treatment for breast cancer

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

This study is testing a new treatment for breast cancer that uses MRI-guided ultrasound to boost the effects of radiation therapy and see how well it works for patients.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 200 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Sunnybrook Health Sciences Centre (other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 1 site (Toronto, Ontario)
• Trial ID: NCT06185972 on ClinicalTrials.gov

What this trial studies

This study aims to evaluate the effectiveness of a novel treatment combining Magnetic Resonance Imaging (MRI)-guided ultrasound-stimulated microbubbles with radiation therapy for patients with breast cancer. The approach utilizes low-power ultrasound to enhance the effects of radiation on tumors, specifically targeting the tumor site to stimulate microbubbles before radiation is administered. The primary goal is to assess the tumor response to this combined treatment, while secondary objectives include monitoring the treatment's early and late effects over time. Participants will be closely monitored at various intervals post-treatment to gather comprehensive data on efficacy and safety.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with biopsy-confirmed invasive breast cancer, including early-stage and locally advanced cases.

Not a fit: Patients with non-invasive breast cancer or those who are not suitable for radiation therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve the effectiveness of radiation therapy for breast cancer patients.

How similar studies have performed: While this approach is innovative, similar studies using ultrasound to enhance radiation therapy have shown promising results, indicating potential for success.

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 \>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.

Where this trial is running

Toronto, Ontario

• Sunnybrook Health Sciences Centre — Toronto, Ontario, Canada (RECRUITING)

Study contacts

• Principal investigator: Dr. Gregory Czarnota, MD, Ph.D. — Sunnybrook Health Sciences Centre
• Study coordinator: Dr.Gregory Czarnota, MD, Ph.D.

Conditions: Breast Cancer, Focused Ultrasound, Microbubbles