Clinical trial NCT06081400: Cryoablation Versus Medical Therapy in Desmoid Tumors Progressing After Watchful Waiting
Official title: A Phase II Multicentric, Randomized Trial Assessing Cryoablation Versus Medical Therapy in Desmoid Tumors Progressing After Watchful Waiting
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Desmoid Tumor
Keywords: Desmoids
Cryoablation
Drug therapy
Cross-Over Studies
Lead sponsor: University Hospital, Strasbourg, France
Sponsor class: OTHER
Collaborators: name: Direction Générale de l'Offre des Soins (DGOS)
First posted: 2023-10-13
Enrollment: 150
Sex: ALL
Minimum age (years): 13
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: "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.


Eligibility criteria: 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)

Primary outcomes:
measure: Rate of non-progressive disease
timeFrame: 12 months after treatment initiation (Day 0+12months)
Secondary outcomes:
measure: Progression-free survival 1
timeFrame: from treatment initiation to PD or 24 months whichever comes first
measure: Rate of patients who cross over to the other arm
timeFrame: 24 months after treatment initiation
measure: Rate of complete response
timeFrame: 12 months after treatment initiation and 12 months after cross-over
measure: Secondary Progression-free survival 2
timeFrame: Through study completion, up to 39 months
measure: Incidence of Treatment-Emergent Adverse Events as assessed by NCI-CTCAE version 5.0 toxicity scale
timeFrame: Through study completion, up to 39 months
measure: QUALITY OF LIFE assessed by EUROQOL EQ 5D before and after treatment
timeFrame: Screening visit, Month 1, Month 2, Month 3, Month 6, Month 9 and Month 12 after treatment initiation
measure: PAIN assessed by brief pain inventory (BPI) before and after treatment
timeFrame: Screening visit, Day 0/Day 1, Month 1, Month 2, Month 3, Month 6, Month 9 and Month 12 after treatment initiation
measure: Health economics assessment
timeFrame: Through study completion, up to 39 months
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: Service d'Oncologie Médicale, Service de Radiologie Interventionnelle, Institut BERGONNIE
city: Caen
country: France
facility: Service d'Oncologie Médicale, Service de Radiologie Interventionnelle-Centre François BACLESSE
city: Dijon
country: France
facility: Service d'Oncologie Médicale -Centre Georges François LECLERC
city: Lyon
country: France
facility: Service d'Oncologie Médicale, Service de Radiologie Interventionnelle-Centre Léon BERARD
city: Marseille
country: France
facility: Service d'Oncologie Médicale, service de Radiologie Interventionnelle,CHU de Marseille, Hopital La Timone
city: Nantes
country: France
facility: Service de Radiologie-CHU de Nantes
city: Nice
country: France
facility: Service d'Oncologie Médicale-Centre Antoine LACASSAGNE
city: Rouen
country: France
facility: Service d'Oncologie Médicale-Centre Henri BECQUEREL
city: Saint-Herblain
country: France
facility: Service d'Oncologie Médicale
city: Strasbourg
country: France
facility: Institut de cancérologie Strasbourg Europe (ICANS)
city: Strasbourg
country: France
facility: Service d'Imagerie Interventionnelle, Hôpitaux Universitaires de Strasbourg , France, 67091
city: Toulouse
country: France
facility: Service d'Oncologie Médicale-Institut Claudius Régaud et Service de Radiologie Interventionnelle, CHU de Toulouse
city: Villejuif
country: France
facility: Service d'Oncologie médicale, Service de Radiologie Interventionnelle- Institut Gustave ROUSSY
Study officials:
affiliation: Hôpitaux Universitaires de Strasbourg
name: Afshin GANGI, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: