MRI-Guided Focused Ultrasound Radiosensitization for Patients With Malignant Melanoma and Non Melanoma Skin Cancer

The objective of this study is to examine the safety profile and therapeutic efficacy of MRI-guided focused ultrasound microbubble therapy and radiotherapy in humans.

Study Overview

• Status: Recruiting
• Conditions: Melanoma
• 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 of this research is to evaluate the safety profile of MRI-guided ultrasound stimulated microbubble treatment and radiation in patients with malignant melanoma. The secondary aim is to evaluate tumour (primary and/or metastasis) response to MRI-guided ultrasound stimulated microbubble treatment and radiation, as measured radiologically within the treated regions.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 1

Contacts and Locations

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

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥18 years
• All biopsy-confirmed malignant melanoma of the skin and non melanoma skin cancer, including metastatic lesions.
• Stage I-IV malignant melanoma and non melanoma skin cancer, per AJCC guidelines (8th Edition).
• Patient referred for palliative radiotherapy/ standard radiotherapy/ neoadjuvant radiotherapy/ SBRT/ hypofractionation.
• Patient on immunotherapy.
• Able to understand and give informed consent. Weight <140kg.
• Target lesion visible by non-contrast MRI.
• Target lesion accessible for MRg-FU procedure.
• Able to communicate sensation during MRg-FU treatment.
• Creatinine within normal institutional limits or creatinine clearance >60 mL/min/1.73 m2 for patients with creatinine levels above the institutional upper limit of norma

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 contrast-enhanced MRI scan - the standard of care criteria
• Target lesion involves the skin surface causing ulceration, bleeding or discharge
• Severe cardiovascular, neurological, renal or hematological chronic disease
• ECOG (Eastern Cooperative Oncology Group) Performance Status ≥ 3. Unable to tolerate required stationary position during treatment
• Cardiac disease or unstable hemodynamics, including myocardial infarction within six months, unstable angina, congestive heart failure, ejection fraction < 50%, 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.
• Severe hypertension (diastolic BP > 100 mmHg)
• 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: Treatment Arm; Malignant Melanoma patients undergoing MRI-guided ultrasound-stimulated microbubble treatment plus radiation therapy	Drug: Definity; Stimulation of Definity microbubbles using Sonalleve device within tumour vasculature; Device: Sonalleve Focused Ultrasound Device; Sonalleve Focused Ultrasound Device

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of toxicity and adverse events, scored on the National Cancer Institute Common Toxicity Criteria (NCI CTCAE 4.03)	The patient will be assessed by a physician investigator and clinical research assistant (CRA) on the MRI-guided focused ultrasound + microbubble (MRgFUS + MB) treatment date and within follow up period of 90 days after treatment.	90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiological response	The secondary aim is to evaluate tumour (primary and/or metastasis) response to MRgFUS + MB and radiation, which will be evaluated by tumour volume change.	2 years

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): June 15, 2022
• Primary Completion (Estimated): July 11, 2025
• Study Completion (Estimated): July 11, 2028

Study Registration Dates

• First Submitted: May 17, 2022
• First Submitted That Met QC Criteria: November 16, 2022
• First Posted (Actual): November 17, 2022

Study Record Updates

• Last Update Posted (Estimated): December 15, 2023
• Last Update Submitted That Met QC Criteria: December 11, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Melanoma; Focused ultrasound; Microbubbles
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Skin Neoplasms
• Other Study ID Numbers: 4877

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