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

Phase 1

Recruiting

• Conditions: Melanoma
• Interventions: Drug: Definity; Device: Sonalleve Focused Ultrasound Device

• Registration Number: NCT05620290
• Lead Sponsor: Sunnybrook Health Sciences Centre

Brief Summary

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.

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 Timeline

• Study First Submitted: 2022-05-17
• Study Start: 2022-06-15
• Study First Submitted QC: 2022-11-16
• Study First Posted: 2022-11-17
• Status Verified: 2023-12
• Last Update Submitted: 2023-12-11
• Last Update Posted: 2023-12-15
• Primary Completion: 2025-07-11
• Study Completion: 2028-07-11

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 20

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment Arm	Sonalleve Focused Ultrasound Device	Malignant Melanoma patients undergoing MRI-guided ultrasound-stimulated microbubble treatment plus radiation therapy
Treatment Arm	Definity	Malignant Melanoma patients undergoing MRI-guided ultrasound-stimulated microbubble treatment plus radiation therapy

Primary Outcome Measures

Name	Time	Method
Incidence of toxicity and adverse events, scored on the National Cancer Institute Common Toxicity Criteria (NCI CTCAE 4.03)	90 days	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.

Secondary Outcome Measures

Name	Time	Method
Radiological response	2 years	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.

Trial Locations

Locations (1)

Sunnybrook Health Sciences Centre; 🇨🇦 Toronto, Ontario, Canada