Evaluation of Percutaneous Cryotherapy in the Treatment of Plexiform Neurofibromas and Unresectable Neurofibromas in Neurofibromatosis Type 1 (CryoNF1)

Evaluation of Percutaneous Cryotherapy in the Treatment of Plexiform Neurofibromas and Unresectable Neurofibromas in Neurofibromatosis Type 1 (NF1)

Neurofibromatosis type 1 (NF1) is an autosomal dominant disease affecting chromosome 17. It is manifested by a neurogenic tumor proliferation that forms cutaneous, subcutaneous or deep neurofibromas.

Neurofibromas can cause functional discomfort, neurogenic pain that is difficult to treat, and severe cosmetic disorders.

Treatment is essentially surgical. It is sometimes a heavy invasive surgery with complicated postoperative follow-up and significant scarring on the aesthetic level. Currently, no systemic treatment has proven its effectiveness in this pathology.

Percutaneous cryotherapy is a cold thermoablation procedure using fine 17 G needles introduced into the lesion after targeting by imaging. This technique is used in the treatment of soft tissue tumors and desmoid tumors.

The treatment of neurofibromas with percutaneous cryotherapy is not well known. Encouraging results (unpublished) have been observed in patients with NF1 treated with cryotherapy at the Léon Bérard Center. The beneficial effect was observed in terms of quality of life (in particular, pain) as well as a decrease in tumor size.

On the basis of this first experience, it appears important to corroborate these preliminary results by a prospective study allowing the use of this technique to treat patients with unresectable or resectable neurofibromas but with mutilating surgery in a NF1 context.

Study Overview

• Status: Recruiting
• Conditions: Neurofibroma; Neurofibroma, Plexiform
• Intervention / Treatment: Device: Cryotherapy

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Patrick COMBEMALE, MD; Phone Number: +33478785996; Email: patrick.combemale@lyon.unicancer.fr
• Study Contact Backup: Name: Amine BOUHAMAMA, MD; Email: amine.bouhamama@lyon.unicancer.fr

Study Locations

• France
  • Lyon, France, 69373
    • Recruiting
    • Centre Leon Berard
    • Contact: Patrick COMBEMALE; Phone Number: +3304 78 78 59 96; Email: patrick.combemale@lyon.unicancer.fr
    • Principal Investigator: Patrick COMBEMALE
    • Sub-Investigator: Amine BOUHAMAMA
    • Sub-Investigator: Frank PILLEUL
    • Sub-Investigator: Mona AMINI-ADLE

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age ≥18 years;
• Patient with neurofibromatosis type 1 according to NIH criteria ;
• Patient with a benign neurofibromatous lesion that is painful and/or generates functional discomfort and is unresectable or with unacceptable scarring ;
• Neutrophils > 1 G/l in the 14 days prior to inclusion;
• Adequate coagulation test with normals values (as judged by the investigator);
• Signed and dated informed consent document indicating that the patient has been informed of all aspects of the trial prior to enrolment
• Covered by a medical insurance;

Exclusion Criteria:

• Patient treated with concomitant chemotherapy and/or targeted therapies ;
• Any contraindication to a percutaneous cryotherapy procedure, including the need for ice formation within 1 cm of the spinal cord, brain or other critical nerve structures, bowel or bladder (unless active or passive thermal protective maneuvers are performed);
• Patient with malignant neurofibroma or MPNST ; CT scan without abnormality and if tumor presents a max SUV T/F>1.5 ratio, targeted biopsy is required to confirm benign or malignant histology.
• Patient with neurofibroma in areas at risk for neurological sequelae;
• Patient with cold urticaria with history of angioedema;
• Any cognitive impairment or condition that may limit the use of numerical scales and quality of life questionnaires;
• Patient for whom follow-up does not seem feasible even in the short term;
• Participation in another clinical trial that may interfere with the evaluation of the primary endpoint;
• Patient under tutorshio, curatorship or deprived of liberty;
• Pregnant or breast-feeding woman;
• Any contraindication to the performance of an MRI
• Patient with dysplastic neurofibroma

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: Percutaneous cryotherapy; Cryoablation of the tumor	Device: Cryotherapy; The cryotherapy treatment lasts approximately 30 minutes during which two 10-minute freezing cycles are performed, separated by a reheating phase. During the freezing phases, the temperature is lowered below -40°C in the ablation zone, a temperature that is lethal for the cells.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the impact of percutaneous cryotherapy on physical health-related quality of life (in patients with inoperable (or operable with mutilating surgery) neurofibroma.	Rate of patients with clinically significant improvement in physical health-related quality of life. A patient will be considered successful if an increase of at least 3 points on the global physical score from the SF-36 questionnaire is observed at least once between baseline and 12 months after cryotherapy.	12 months after cryotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess each quality of life dimension of the Short Form-36 (SF-36) questionnaire;	The score for each dimension, the mental global score and the physical global score from the SF-36 questionnaire	At baseline, at Month1 post cryotherapy ; Month 3 post cryotherapy; Month 6 post cryotherapy, Month 9 post cryotherapy, Month 12 post cryotherapy, Month 18 post cryotherapy and Month 24 post post cryotherapy ;
To evaluate the tumor response	Local control rate using REiNS and RECIST 1.1 criteria	Month 3, Month 6, Month 9, Month 12, Month 18 , and Month 24 after cryotherapy
To evaluate the functional discomfort	Functional discomfort assessed by a Likert scale	At baseline, Month 1; Month 3; Month 6, Month 9, Month12, Month18 and Month 24 post cryotherapy
To evaluate the patients' pain	Pain assessed by the Brief Pain Inventory-Short Form (BPI-SF) questionnaire	At baseline, Month 1; Month 3; Month 6, Month 9, Month 12, Month 18 and Month 24 post cryotherapy
To evaluate the safety of percutaneous cryotherapy	Tolerance of cryotherapy treatment assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0	From cryotherapy to 24 months after cryotherapy
To evaluate patients' satisfaction	Patient satisfaction with their first cryotherapy treatment assessed by a Likert scale	At Month 12 post-cryotherapy;
To evaluate patients self-esteem	Self-esteem assessed by a questionnaire consisting of items evaluated on a Likert scale	at baseline, Month 1; Month 3; Month 6, Month 9, Month12, Month 18 and Month 24 post-cryotherapy
To evaluate the need for multiple percutaneous cryotherapy procedures in case of incomplete response on the target lesion;	Rate of patients for whom at least one additional percutaneous cryotherapy procedure is required	From cryotherapy to 24 months after cryotherapy
To evaluate operating room occupancy time.	Median operating room occupancy time calculated as the difference between operating room exit time and operating room entry time.	At Day 0

Collaborators and Investigators

• Sponsor: Centre Leon Berard

Study record dates

Study Major Dates

• Study Start (Actual): February 14, 2022
• Primary Completion (Estimated): February 7, 2026
• Study Completion (Estimated): February 7, 2027

Study Registration Dates

• First Submitted: December 21, 2021
• First Submitted That Met QC Criteria: January 19, 2022
• First Posted (Actual): January 20, 2022

Study Record Updates

• Last Update Posted (Estimated): February 9, 2024
• Last Update Submitted That Met QC Criteria: February 8, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Genetic Diseases, Inborn; Neuromuscular Diseases; Neurodegenerative Diseases; Neoplasms, Nerve Tissue; Peripheral Nervous System Diseases; Nervous System Neoplasms; Heredodegenerative Disorders, Nervous System; Neoplastic Syndromes, Hereditary; Nerve Sheath Neoplasms; Neurocutaneous Syndromes; Peripheral Nervous System Neoplasms; Neurofibromatoses; Neurofibromatosis 1; Neurofibroma; Neurofibroma, Plexiform
• Other Study ID Numbers: ET21-198

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