Cryoablation Versus Medical Therapy in Desmoid Tumors Progressing After Watchful Waiting (CRYODESMO-02)

A Phase II Multicentric, Randomized Trial Assessing Cryoablation Versus Medical Therapy in Desmoid Tumors Progressing After Watchful Waiting

"Wait & see" is currently the standard of care of recently diagnosed desmoid tumors (DT). In case of progression or symptomatic disease, medical therapy is nowadays widely used including chemotherapy.

Cryoablation has proven to be beneficial for the treatment of large, progressive and symptomatic DT.

This randomized phase II trial aims to compare cryoablation versus medical therapy in DT patients progressing after the "wait & see" period. Moreover, a cross-over design has been anticipated to allow all patients to undergo cryoablation if necessary.

Study Overview

• Status: Recruiting
• Conditions: Desmoid Tumor
• Intervention / Treatment: Procedure: Cryoablation; Drug: Chemotherapy drug

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Afshin GANGI, MD,PhD; Phone Number: 33 0369550304; Email: afshin.gangi@chru-strasbourg.fr
• Study Contact Backup: Name: Roberto Luigi CAZZATO, MD; Phone Number: 33 0369550304; Email: RobertoLuigi.CAZZATO@chru-strasbourg.fr

Study Locations

• France
  • Bordeaux, France, 33000
    • Not yet recruiting
    • Service d'Oncologie Médicale, Service de Radiologie Interventionnelle, Institut BERGONNIE
    • Contact: Maud TOULMONDE, MD
    • Principal Investigator: Maud Toulmonde, MD
  • Caen, France, 14076
    • Not yet recruiting
    • Service d'Oncologie Médicale, Service de Radiologie Interventionnelle-Centre François BACLESSE
    • Contact: Marie-Aude THENINT, MD
    • Principal Investigator: Marie-Aude THENINT, MD
  • Dijon, France, 21079
    • Not yet recruiting
    • Service d'Oncologie Médicale -Centre Georges François LECLERC
    • Principal Investigator: Alice HERVIEU, MD
    • Contact: Alice HERVIEU, MD
  • Lyon, France, 69373
    • Not yet recruiting
    • Service d'Oncologie Médicale, Service de Radiologie Interventionnelle-Centre Léon BERARD
    • Contact: Mehdi BRAHMI, MD
    • Principal Investigator: Mehdi BRAHMI, MD
  • Marseille, France, 13385
    • Not yet recruiting
    • Service d'Oncologie Médicale, service de Radiologie Interventionnelle,CHU de Marseille, Hopital La Timone
    • Contact: Florence DUFFAUD, MD, PhD
    • Principal Investigator: Florence DUFFAUD, MD, PhD
  • Nantes, France, 44000
    • Not yet recruiting
    • Service de Radiologie-CHU de Nantes
    • Contact: Arthur DAVID, MD
    • Principal Investigator: Arthur DAVID, MD
  • Nice, France, 06189
    • Not yet recruiting
    • Service d'Oncologie Médicale-Centre Antoine LACASSAGNE
    • Contact: Agnès DUCOULOMBIER, MD
    • Principal Investigator: Agnès DUCOULOMBIER
  • Rouen, France, 76038
    • Not yet recruiting
    • Service d'Oncologie Médicale-Centre Henri BECQUEREL
    • Contact: Cécile GUILLEMET, MD
    • Principal Investigator: Cécile GUILLEMET, MD
  • Saint-Herblain, France, 44805
    • Not yet recruiting
    • Service d'Oncologie Médicale
    • Contact: Emmanuelle BOMPAS, MD
    • Principal Investigator: Emmnauelle BOMPAS, MD
  • Strasbourg, France, 67033
    • Recruiting
    • Institut de cancerologie Strasbourg Europe (ICANS)
    • Contact: Jean-Emmanuel KURTZ, MD PhD
    • Principal Investigator: Jean-Emmanuel KURTZ
    • Sub-Investigator: Sophie MARTIN
  • Strasbourg, France, 67091
    • Recruiting
    • Service d'Imagerie Interventionnelle, Hôpitaux Universitaires de Strasbourg , France, 67091
    • Contact: Afshin GANGI, MD, PhD
    • Principal Investigator: Afshin GANGI, MD, PhD
    • Sub-Investigator: Roberto Luigi CAZZATO, MD
    • Sub-Investigator: Julien GARNON, MD PhD
  • Toulouse, France, 31059
    • Not yet recruiting
    • Service d'Oncologie Médicale-Institut Claudius Régaud et Service de Radiologie Interventionnelle, CHU de Toulouse
    • Principal Investigator: Thibaud VALENTIN, MD
    • Contact: Thibaud VALENTIN, MD
  • Villejuif, France, 94800
    • Not yet recruiting
    • Service d'Oncologie médicale, Service de Radiologie Interventionnelle- Institut Gustave ROUSSY
    • Contact: Frédéric DESCHAMPS, MD
    • Principal Investigator: Frédéric DESCHAMPS, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Subject (male or female) with extra-peritoneal desmoid tumor (confirmed by prior biopsy by an experienced pathologist within the RRePS network)
• 13 years of age or older
• Measurable viable tumor (according to the mRECIST criteria using MRI. The baseline MRI imaging is mandatory in the 2 months prior to treatment initiation (D0).
• Progressive disease (according to the mRECIST criteria) after the watchful waiting period or significant increase in symptoms requiring an active therapy, as advised in a multidisciplinary sarcoma tumor board
• Tumor deemed accessible for cryoablation procedure by the operator in a type I center. (In pediatric cases, a careful site tumor analysis will be performed with interventional radiologist to ensure for limited consequence of cryoablation in pediatric patients especially regarding growth plates).
• 100 % of destruction of the tumor achievable in one procedure of cryoablation with 1cm security margin according to assessment by referral center (type 1) for cryoablation
• ECOG performance status 0-2 at inclusion visit
• Biological and hematological parameters (neutrophils ≥ 1,5.109/L ; platelet count ≥ 100.109/L ; no significant hemostatic abnormalities) in the 4 weeks prior to treatment initiation (D0)
• Subject able to understand the objectives and risks of the research and to give dated and signed informed consent. For minors, the consent of the 2 parents must be obtained.
• Subject affiliated to a social health insurance plan
• For a woman of childbearing age: negative blood pregnancy test at screening/inclusion visit
• Subject agreeing to use a contraceptive method:

Exclusion criteria:

• Intra-peritoneal desmoid tumor
• Known hypersensitivity to vinorelbine or other vinca-alkaloids, or other constituents to navelbine, to vinblastine, to methotrexate or any excipients, current or recent (within 2 weeks) severe infection, severe renal failure, severe hepatic injury, chronic respiratory failure, concomitant treatment with: yellow fever vaccine, prophylactic treatment with phenytoin, trimethoprim, probenecid, acetylsalicylic acid, phenylbutazone.
• Any contra-indication for the procedure as stated by the interventional radiologist in terms of tumor size, proximity to neural/vascular structures or adjacent organs at risk making the procedure at unacceptable risk
• Impaired hemostasis, that may interfere with the conduct of the cryoablation
• Concurrent participation in other experimental studies that could affect endpoints of the present study
• Concurrent use of any antitumor agent or NSAIDs, penicillins, PPIs, acitretin, ciprofloxacin, azote protoxide
• Contraindication to any form of sedation
• Hypersensitivity to gadoteric acid, meglumine or any drug containing gadolinium
• Others contra-indications to MRI
• Pregnancy or breastfeeding
• Impossibility to give the subject informed information (subject in an emergency situation, patient with comprehension difficulties ...)
• Psychiatric disorders
• Incompetent subject (subject to a legal protection measure: curatorship, guardianship, future protection mandate, family habilitation)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cryoablation; One single cryoablation of the desmoid tumor at Day 0	Procedure: Cryoablation; Percutaneous imaging-guided cryoablation
Active Comparator: Medical therapy; Chemotherapy: at the investigator's discretion: either; methotrexate 30mg/m² + vinblastine 6mg/m² (IV infusion) once/week for 6 months, then every other week from months 7 to 12, or; vinorelbine 90mg/week (per os: 3x30mg, soft capsules) for 12 months.	Drug: Chemotherapy drug; Either : methotrexate 30mg/m² + vinblastine 6mg/m² (IV infusion) once/week for 6 months, then every other week from months 7 to 12, or vinorelbine 90mg/week (per os: 3x30mg, soft capsules) for 12 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of non-progressive disease	Rates of non-progressive disease (sum of complete response (CR), partial response (PR), and stable disease (SD) according to modified RECIST criteria)	12 months after treatment initiation (Day 0+12months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival 1	Progression-free survival 1 (PFS1: from the beginning of cryoablation or medical therapy to first disease progression) in cryoablation and medical therapy group	from treatment initiation to PD or 24 months whichever comes first
Rate of patients who cross over to the other arm		24 months after treatment initiation
Rate of complete response	Rate of complete response at 12 months in cryoablation and medical therapy group with and without a cross-over treatment	12 months after treatment initiation and 12 months after cross-over
Secondary Progression-free survival 2	Secondary Progression-free survival 2 (PFS 2: from the cross-over to second disease progression) in cryoablation and medical therapy group	Through study completion, up to 39 months
Incidence of Treatment-Emergent Adverse Events as assessed by NCI-CTCAE version 5.0 toxicity scale	The occurrence of complications and adverse reactions according to the classification of the NCI-CTCAE version 5.0 toxicity scale	Through study completion, up to 39 months
QUALITY OF LIFE assessed by EUROQOL EQ 5D before and after treatment	EUROQOL EQ 5D will be used; score ranging from 1 (good quality of life) to 5 (poor quality of life)	Screening visit, Month 1, Month 2, Month 3, Month 6, Month 9 and Month 12 after treatment initiation
PAIN assessed by brief pain inventory (BPI) before and after treatment	BPI will be used; score ranging from 0 (no pain) to 10 (high pain)	Screening visit, Day 0/Day 1, Month 1, Month 2, Month 3, Month 6, Month 9 and Month 12 after treatment initiation
Health economics assessment	cost and incremental cost utility ratio	Through study completion, up to 39 months

Collaborators and Investigators

• Sponsor: University Hospital, Strasbourg, France
• Collaborators: Direction Générale de l'Offre des Soins (DGOS)
• Investigators: Principal Investigator: Afshin GANGI, MD, PhD, Hôpitaux Universitaires de Strasbourg

Study record dates

Study Major Dates

• Study Start (Actual): March 4, 2024
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): June 1, 2029

Study Registration Dates

• First Submitted: August 31, 2023
• First Submitted That Met QC Criteria: October 6, 2023
• First Posted (Actual): October 13, 2023

Study Record Updates

• Last Update Posted (Actual): March 18, 2024
• Last Update Submitted That Met QC Criteria: March 15, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Drug therapy; Cryoablation; Cross-Over Studies; Desmoids
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Connective Tissue; Neoplasms, Fibrous Tissue; Fibroma; Fibromatosis, Aggressive
• Other Study ID Numbers: 7361 (IRB)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No