HIFU Treatment of Cutaneous Neurofibromas in Neurofibromatosis Type 1: Safety and Efficacy

Cutaneous Neurofibroma Clinical Trial

— cNF-HFU2101  

Official title:

High-Intensity Focused Ultrasound (HIFU), a Novel Method for Treatment of Cutaneous Neurofibromas in Neurofibromatosis Type 1: Safety and Efficacy

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05119582
• Other study ID #: CIV-21-09-037759
• Status: Active, not recruiting
• Phase: N/A
• Start date: April 13, 2022
• Est. completion date: January 1, 2024

Study information

• Verified date: August 2023
• Source: Bispebjerg Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The overall objective is to demonstrate safety and efficacy of HIFU treatment of cutaneous neurofibromas located close to the surface of the skin in patients with the genetic disease Neurofibromatosis Type 1. The study will use a new investigational equipment that has been specially developed for dermatological therapy.

The study includes 20 patients in total distributed between the two centers, each having a minimum of 8 cutaneous neurofibromas eligible for treatment. All participants are adults (over 18 years) of both sexes.

The new treatment method is based on focusing intensive ultrasound just below the skin surface. This creates a very fast localized heating in small and very well-defined volumes containing neurofibroma tissue. This heating destroys or weakens the tissue, and the body's natural processes will subsequently transport affected cells away through the lymphatic and vascular systems. During the healing-process, the rejected tissue is replaced by new skin cells that are not expected to be fibrous.

The treatment is intended to be carried out without breaking the skin surface, and open wounds are therefore avoided. This is an essential advantage of the method compared to all existing therapies, which are based on physical removal of tumors through an open skin surface (e.g. surgery or laser therapy). Complications with risk of pain, infection and scarring will therefore be significantly reduced with the new proposed method.

The treatment is carried out by sending focused ultrasound from the handpiece of the equipment into the target area with neurofibromas. The equipment is set to send doses of approximately 150 milliseconds (0.15 seconds). The skin area and HIFU doses can be followed on the system computer screen and will be placed side-by-side with approximately 1-2 millimeter spacing. To achieve good energy transfer from handpiece to skin, ordinary ultrasound gel is used. There are no other special pre-treatments or preparations for the process. HIFU treatment is expected to be less painful than other treatments used. The treatment is quick, and typically takes less than 1 minute for a each area the size of a typical neurofibroma.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 20
• Est. completion date: January 1, 2024
• Est. primary completion date: January 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Males and females 18 years of age or older.

• Patients with a clinical diagnosis of NF1 based on germline genetic testing or by meeting the internationally recognized criteria given by the Clinical Care Advisory Board of the National Neurofibromatosis Foundation (now the Children's Tumor Foundation)

• Patients must be seeking active treatment for cNF.

• Patients must have = 8 paired cNF that are visible and measure a minimum of 2 mm in size. These must be in areas amenable to treatment and surveillance.

• Patients with Fitzpatrick Type I to VI skin-type

• Able and willing to comply with all visits, treatments, evaluations, schedules, and requirements.

• Patients shall have received oral and written study information, accepted participation and signed the informed consent document.

• Patients who are willing and mentally and physically capable to understand and follow the treatment and follow-up schedule including post-treatment care instructions.

• Patients who are willing to have photographs and images taken of the treated lesions to be used anonymously or coded in evaluations and publications.

Exclusion Criteria:

• Patients who are undergoing other treatment modalities or investigational agents for their cNF lesions.

• Individuals who cannot give informed consent or adhere to study schedule.

• Patients who are actively tanning during the course of the study.

• Patients with adverse reactions to compounds of any external agent in use.

• Patients with known allergy to injectable anesthetics (relevant for biopsy only).

• Patients with any condition which, in the Investigator's opinion, would make it unsafe (for the participant or study personnel) to treat the participant as part of this research study.

• Patients, where target treatment may cause the acoustic beam to enter the eye.

• Pregnant females, due to possible discomfort with the procedure even though the procedure is localized and there is no new drug.

• Patients with tendency for keloid and hypertrophic scar formation .

• Patients with impaired wound healing.

• Patients with any other acute or chronic condition which, in the opinion of the investigator, could interfere with the conduct of the study.

Related Conditions & MeSH terms

• Cutaneous Neurofibroma
• Neurofibroma
• Neurofibromatoses
• Neurofibromatosis 1

Intervention

Device:
• TOOsonix System ONE-M
Selected neurofibromas will be treated by high intensity focused ultrasound. Untreated fibromas will be used for controls.

Locations

Country	Name	City	State
Denmark	Bispebjerg Hospital	Copenhagen	Hovedstaden
Sweden	Sahlgrenska University Hospital	Gothenburg

Sponsors (2)

Lead Sponsor	Collaborator
Joergen Serup	Sahlgrenska University Hospital, Sweden

Countries where clinical trial is conducted

Denmark,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Short Term Safety Profile - Adverse Events	The grade of any adverse events (AE) requiring medical intervention within three months of treatment should be low. Device-based treatment will be considered tolerable if less than 30% of participants treated have an "Overall AE Score" larger than Grade 2 AE at the 3-month follow-up (visit 4).; Measured by a grading scale based on Common Terminology Criteria for Adverse Events (CTCAE), U.S. Department of health and human services, Ver 5.0, Nov 27, 2017.	3 months
Primary	Long Term Safety Profile - Healing	The rate and nature of spontaneous healing of the treated cNF lesion and any safety related event including potential wound formation and wound healing should be equivalent to expectations from alternative method(s). Safety evaluation includes rating of treatment-associated sequele by end of study, e.g. dyspigmentation and scarring and overall investigator rating compared to expectations.; Measured on 5-point grading from Very Unsatisfied to Very Satisfied.	9 months
Secondary	Long Term Safety Profile - Adverse Events	Any objective adverse effect or event, local or systemic, related to the treatment and the investigational device.; Measured by a grading scale based on Common Terminology Criteria for Adverse Events (CTCAE), U.S. Department of health and human services, Ver 5.0, Nov 27, 2017.	9 months