Cryoablation Versus Medical Therapy in Desmoid Tumors Progressing After Watchful Waiting

Study Overview
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Brief Summary
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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.

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

Conditions
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Desmoid Tumor

Intervention / Treatment
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* Procedure: Cryoablation
* Drug: Chemotherapy drug


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 13 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cryoablation<br>One single cryoablation of the desmoid tumor at Day 0 | Procedure: Cryoablation<br>* Percutaneous imaging-guided cryoablation<br>|
| Active Comparator: Medical therapy<br>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<br>* 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.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Desmoids, Cryoablation, Drug therapy, Cross-Over Studies