Multicentric phase III trial comparing two strategies in intermediate-risk differentiated thyroid cancer patients: Systematic radioiodine administration versus decision of radioiodine treatment guided by a post-operative work-up based on serum Tg values and diagnostic RAI scintigraphy
- Conditions
- intermediate-risk differentiated thyroid cancer patients
- Registration Number
- 2024-514603-34-00
- Lead Sponsor
- Centre Francois Baclesse
- Brief Summary
- To assess whether a strategy of RAI-treatment guided by a post-operative work-up is non-inferior to a systematic RAI-treatment strategy in terms of excellent response rate at 3 years post-randomization in a “low-risk” subgroup of patients within the intermediate-risk category
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing, recruiting
- Sex
- Not specified
- Target Recruitment
- 476
• Subgroup of patients with differentiated thyroid cancer and intermediate-risk defined as follows according to TNM 2017: o Papillary thyroid cancer (PTC) without aggressive subtype, follicular thyroid cancer (FTC) (with < 4 foci of vascular invasion) or Hürthle cell carcinoma (HCC) o T1b or T2 with minimal extra-thyroid extension into the perithyroidal soft tissues and/or pN1 with largest nodal dimension between 2 and 10 mm, without extra-capsular invasion and with a number of metastatic nodes ≤ 10 o T1aN1 with largest nodal dimension between 2 and 10 mm, without extra-capsular invasion and with a number of metastatic nodes ≤ 10
• Signed informed consent form
• Patient who agrees to be followed annually during 5 years
• Patient affiliated to the French social security system
• Patient treated by total thyroidectomy with macroscopically complete tumor resection (R0 or R1) ± neck dissection
• Total thyroidectomy performed within 6 to 14 weeks before randomization
• Patient with or without anti-thyroglobulin antibodies (TgAb)
• No known distant metastases
• Normal post-operative neck ultrasound (US) or if doubtful US, negative cytology and normal Tg value (<10 ng/ml) in FNA washout fluid
• Post-operative LT4 treatment initiated at least 6 weeks before randomization
• Performance Status 0 or 1
• Patients aged 18 years or older
• Patients with: o medullary or anaplastic thyroid cancer o or poorly differentiated carcinoma o or well differentiated FTC with at least 4 foci of vascular invasion o or PTC with aggressive variants (tall cell or columnar cell carcinoma, diffuse sclerosing papillary, hobnail variant) o NIFTP (Noninvasive follicular thyroid neoplasm with papillary-like nuclear features)
• History of malignancy in the past 3 years, except skin cancer excluding melanoma, carcinoma in situ of the cervix. Any other solid tumor or lymphoma (without bone marrow involvement) must have been treated and not have shown signs of recurrence for at least 3 years
• Low-risk or high-risk DTC patients according to ATA 2015, and intermediate-risk patients with extra-thyroid extension into the perithyroidal muscles (pT3b according to pTNM 2017), and/or pN1 with nodal largest dimension >10 mm or with extra-capsular invasion or more than 10 metastatic nodes. This excludes the following patients: o All pT3 or pT4 o pT1aN0/x with or without minimal extra-thyroid extension o pT1bN0/x, pT2N0/Nx without minimal extra-thyroid extension o pT1aN1 or pT1bN1 or pT2N1 without extra-thyroid extension and with nodal largest dimension <2mm o pT1aN1 or pT1bN1 or pT2N1 without extra-thyroid extension and with nodal largest dimension >10mm o Surgery considered as macroscopically incomplete (R2)
• Patients who have undergone lobectomy only
• Post-operative neck US with metastatic lymph-nodes confirmed by cytology or by increased Tg (>10 ng/ml) in FNA washout fluid
• Drugs affecting thyroid function including iodinated contrast agents in the 6 weeks prior to randomization. Amiodarone should have been stopped at least 1 year before randomization.
• Previous RAI treatment for thyroid cancer
• Pregnant or lactating women
• Any associated geographical, social or psychopathological condition that could compromise the patient's ability to participate in the study
• Patient deprived of liberty or placed under the authority of a tutor
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method - The primary endpoint is the rate of patients with excellent response (normal neck ultrasonography and Tg/LT4 <0.2 ng/mL and absence of TgAb and if performed, no abnormalities on other imaging modalities), at 3 years post-randomization - The primary endpoint is the rate of patients with excellent response (normal neck ultrasonography and Tg/LT4 <0.2 ng/mL and absence of TgAb and if performed, no abnormalities on other imaging modalities), at 3 years post-randomization
- Secondary Outcome Measures
Name Time Method - Excellent response rate at 1 and 5 years post-randomization, defined as above, will be used for non-inferiority comparison - Excellent response rate at 1 and 5 years post-randomization, defined as above, will be used for non-inferiority comparison
- The scores on HRQoL, anxiety and fear of cancer recurrence will be calculated according to the corresponding scoring manual from the various questionnaires at inclusion, end of diagnostic assessment, end of treatment (for treated patients), 1 year and 3 years. The lachrymal, nasal and salivary glands toxicities will be evaluated from specific questionnaires at inclusion, end of diagnostic assessment, end of treatment (for treated patients), 1 year and 3 years - The scores on HRQoL, anxiety and fear of cancer recurrence will be calculated according to the corresponding scoring manual from the various questionnaires at inclusion, end of diagnostic assessment, end of treatment (for treated patients), 1 year and 3 years. The lachrymal, nasal and salivary glands toxicities will be evaluated from specific questionnaires at inclusion, end of diagnostic assessment, end of treatment (for treated patients), 1 year and 3 years
- Supplemental treatments (surgery, RAI administration or others) performed within 5 years post-randomization in both groups. The response to these treatments will be defined according to the 2015 ATA guidelines: excellent response, biochemical incomplete response, structural incomplete response, and indeterminate response - Supplemental treatments (surgery, RAI administration or others) performed within 5 years post-randomization in both groups. The response to these treatments will be defined according to the 2015 ATA guidelines: excellent response, biochemical incomplete response, structural incomplete response, and indeterminate response
- Costs within 5 years post-randomization in both groups, from the French collective perspective, taking into account the resources such as: External consultations, hospitalizations Imaging exams (neck-US, scintigraphy, CT scans…) Biological exams Transportation related to the care Study treatments: I131 and rhTSH Treatment for possible recurrence (surgery, RAI administration or others) Sick leave related to thyroid cancer - Costs within 5 years post-randomization in both groups, from the French collective perspective, taking into account the resources such as: External consultations, hospitalizations Imaging exams (neck-US, scintigraphy, CT scans…) Biological exams Transportation related to the care Study treatments: I131 and rhTSH Treatment for possible recurrence (surgery, RAI administration or others) Sick leave related to thyroid cancer
- The results of diagnostic and post-therapeutic scintigraphy (in the guided follow-up group) - The results of diagnostic and post-therapeutic scintigraphy (in the guided follow-up group)
- The proportion of patients for whom the results of the diagnostic RAI scintigraphy have changed the decision-making for RAI treatment (in the guided follow-up group) - The proportion of patients for whom the results of the diagnostic RAI scintigraphy have changed the decision-making for RAI treatment (in the guided follow-up group)
- The post-operative serum Tg levels on Levothyroxine treatment (Tg/LT4) and after rhTSH (Tg/rhTSH) to assess their predictive value on the presence of RAI-avid lesions in the RAI group and on the rate of excellent response at 3 years in both groups - The post-operative serum Tg levels on Levothyroxine treatment (Tg/LT4) and after rhTSH (Tg/rhTSH) to assess their predictive value on the presence of RAI-avid lesions in the RAI group and on the rate of excellent response at 3 years in both groups
- The excellent response rate at 3 and 5 years after randomization in case of supplemental treatments - The excellent response rate at 3 and 5 years after randomization in case of supplemental treatments
- The predictive values of somatic molecular markers (especially BRAF and TERTp) on the risk of persistent disease - The predictive values of somatic molecular markers (especially BRAF and TERTp) on the risk of persistent disease
Trial Locations
- Locations (27)
Centre Leon Berard
🇫🇷Lyon, France
Centre Hospitalier Universitaire De Toulouse
🇫🇷Toulouse, France
CHRU De Nancy
🇫🇷Vandoeuvre Les Nancy Cedex, France
Centre Hospitalier Regional Et Universitaire De Brest
🇫🇷Brest, France
Centre Hospitalier Regional De Marseille
🇫🇷Marseille, France
Centre Jean Perrin
🇫🇷Clermont-Ferrand, France
Centre Hospitalier Universitaire De La Guadeloupe
🇫🇷Les Abymes, France
Institut Gustave Roussy
🇫🇷Villejuif Cedex, France
Centre Francois Baclesse
🇫🇷Caen Cedex 5, France
Centr Georges Francois Leclerc
🇫🇷Dijon, France
Scroll for more (17 remaining)Centre Leon Berard🇫🇷Lyon, FranceAnne-laure GIRAUDETSite contact0469856001anne-laure.giraudet@lyon.unicancer.fr