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Cryoablation Versus Medical Therapy in Desmoid Tumors Progressing After Watchful Waiting

Not Applicable
Recruiting
Conditions
Desmoid Tumor
Interventions
Procedure: Cryoablation
Drug: Chemotherapy drug
Registration Number
NCT06081400
Lead Sponsor
University Hospital, Strasbourg, France
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
150
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)
Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
CryoablationCryoablationOne single cryoablation of the desmoid tumor at Day 0
Medical therapyChemotherapy drugChemotherapy: 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.
Primary Outcome Measures
NameTimeMethod
Rate of non-progressive disease12 months after treatment initiation (Day 0+12months)

Rates of non-progressive disease (sum of complete response (CR), partial response (PR), and stable disease (SD) according to modified RECIST criteria)

Secondary Outcome Measures
NameTimeMethod
Secondary Progression-free survival 2Through study completion, up to 39 months

Secondary Progression-free survival 2 (PFS 2: from the cross-over to second disease progression) in cryoablation and medical therapy group

Incidence of Treatment-Emergent Adverse Events as assessed by NCI-CTCAE version 5.0 toxicity scaleThrough study completion, up to 39 months

The occurrence of complications and adverse reactions according to the classification of the NCI-CTCAE version 5.0 toxicity scale

PAIN assessed by brief pain inventory (BPI) before and after treatmentScreening visit, Day 0/Day 1, Month 1, Month 2, Month 3, Month 6, Month 9 and Month 12 after treatment initiation

BPI will be used; score ranging from 0 (no pain) to 10 (high pain)

Health economics assessmentThrough study completion, up to 39 months

cost and incremental cost utility ratio

Progression-free survival 1from treatment initiation to PD or 24 months whichever comes first

Progression-free survival 1 (PFS1: from the beginning of cryoablation or medical therapy to first disease progression) in cryoablation and medical therapy group

QUALITY OF LIFE assessed by EUROQOL EQ 5D before and after treatmentScreening visit, Month 1, Month 2, Month 3, Month 6, Month 9 and Month 12 after treatment initiation

EUROQOL EQ 5D will be used; score ranging from 1 (good quality of life) to 5 (poor quality of life)

Rate of complete response12 months after treatment initiation and 12 months after cross-over

Rate of complete response at 12 months in cryoablation and medical therapy group with and without a cross-over treatment

Rate of patients who cross over to the other arm24 months after treatment initiation

Trial Locations

Locations (13)

Service d'Oncologie Médicale, Service de Radiologie Interventionnelle-Centre François BACLESSE

🇫🇷

Caen, France

Service de Radiologie-CHU de Nantes

🇫🇷

Nantes, France

Service d'Oncologie médicale, Service de Radiologie Interventionnelle- Institut Gustave ROUSSY

🇫🇷

Villejuif, France

Institut de cancérologie Strasbourg Europe (ICANS)

🇫🇷

Strasbourg, France

Service d'Oncologie Médicale, service de Radiologie Interventionnelle,CHU de Marseille, Hopital La Timone

🇫🇷

Marseille, France

Service d'Oncologie Médicale-Centre Antoine LACASSAGNE

🇫🇷

Nice, France

Service d'Oncologie Médicale -Centre Georges François LECLERC

🇫🇷

Dijon, France

Service d'Oncologie Médicale, Service de Radiologie Interventionnelle, Institut BERGONNIE

🇫🇷

Bordeaux, France

Service d'Oncologie Médicale, Service de Radiologie Interventionnelle-Centre Léon BERARD

🇫🇷

Lyon, France

Service d'Oncologie Médicale-Centre Henri BECQUEREL

🇫🇷

Rouen, France

Service d'Oncologie Médicale

🇫🇷

Saint-Herblain, France

Service d'Imagerie Interventionnelle, Hôpitaux Universitaires de Strasbourg , France, 67091

🇫🇷

Strasbourg, France

Service d'Oncologie Médicale-Institut Claudius Régaud et Service de Radiologie Interventionnelle, CHU de Toulouse

🇫🇷

Toulouse, France

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