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

• ClinicalTrials.gov Identifier: NCT04431674
• Recruitment Status: Recruiting
• First Posted: June 16, 2020
• Last Update Posted: November 10, 2020
• Sponsor: Sunnybrook Health Sciences Centre
• Information provided by (Responsible Party): Dr. Gregory Czarnota, Sunnybrook Health Sciences Centre

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Breast Cancer	Drug: Definity Suspension for Injection	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Prospective, Single-Centre, Single-Arm, Non-Randomized, Phase-I MRI-Guided Ultrasound Stimulated Microbubbles Radiation Treatment for Patients with Chest Wall and Breast Cancer
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Novel MRI-Guided Ultrasound Stimulated Microbubble Radiation Treatment for Patients With Chest-wall and Locally-Advanced Breast Cancer
• Actual Study Start Date: May 1, 2020
• Estimated Primary Completion Date: May 1, 2022
• Estimated Study Completion Date: May 1, 2024

Arms and Interventions

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.	Drug: Definity Suspension for Injection; MRI-guided ultrasound-stimulated microbubble-treatment

Outcome Measures

Primary Outcome Measures :

1. 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

Secondary Outcome Measures :

1. 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Age ≥ 18 years
• All biopsy-confirmed invasive ductal, invasive lobular and other rare histologic types of carcinoma within past three months
• Patients with early stage Breast cancer, or LABC ; i.e., Stage IIA - IIIC cancers (T2 N0 M0 to Any T, N3, M0) 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 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
• Patient with normal coagulation profile, CBC, liver profile (bilirubin/ ALT/ALP), electrolytes (sodium, potassium, chloride, CO2 total), BUN and creatinine.

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)
• Patients concurrently taking anti-coagulant therapy like antiplatelets or vitamin K inhibitors or heparin derivatives
• History of bleeding disorder, coagulopathy
• Severely impaired renal function with estimated glomerular filtration rate < 30ml/min/1.73m2 and/or on dialysis

Contacts and Locations

Locations

Canada, Ontario

Sunnybrook Health Sciences Centre; Recruiting

Toronto, Ontario, Canada, M4N 3M5

Contact: Gregory J Czarnota, PhD, MD (416) 480-6128 gerogory.czarnota@sunnybrook.ca

Sponsors and Collaborators

Sunnybrook Health Sciences Centre

More Information

• Responsible Party: Dr. Gregory Czarnota, Senior Scientist, MD, Sunnybrook Health Sciences Centre
• ClinicalTrials.gov Identifier: NCT04431674
• Other Study ID Numbers: 077-2019
• First Posted: June 16, 2020
• Last Update Posted: November 10, 2020
• Last Verified: November 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Keywords provided by Dr. Gregory Czarnota, Sunnybrook Health Sciences Centre:

Breast Cancer; Focused ultrasound; Microbubbles

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases