Systematic Radioiodine Administration Versus Decision of Radioiodine Treatment Guided by a Post-operative Work-up

Study Overview
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Brief Summary
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This trial is 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

Official Title
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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
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Thyroid Cancer, Intermediate Risk

Intervention / Treatment
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* Drug: Systematic RAI-treatment
* Other: Decision of RAI-treatment guided by a post-operative assessment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subgroup of patients with differentiated thyroid cancer and intermediate-risk defined as follows according to TNM 2017: Papillary thyroid cancer (PTC) without aggressive subtype, follicular thyroid cancer (FTC) (with < 4 foci of vascular invasion) or Hürthle cell carcinoma (HCC) 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 T1aN1 with largest nodal dimension between 2 and 10 mm, without extra-capsular invasion and with a number of metastatic nodes ≤ 10 Patient treated by total thyroidectomy with macroscopically complete tumor resection (R0 or R1) ± neck dissection Total thyroidectomy performed within 6 to 14 10 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 Signed informed consent form Patient who agrees to be followed annually during 5 years Patient affiliated to the French social security system Exclusion Criteria: • Patients with: medullary or anaplastic thyroid cancer or poorly differentiated carcinoma or well differentiated FTC with at least more than 4 foci of vascular invasion or PTC with aggressive variants (tall cell or columnar cell carcinoma, diffuse sclerosing papillary, hobnail variant) NIFTP (Noninvasive follicular thyroid neoplasm with papillary-like nuclear features) • 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: All pT1a, pT3 or pT4 pT1aN0/x with or without minimal extra-thyroid extension pT1bN0/x, pT2N0/Nx without minimal extra-thyroid extension pT1aN1 or pT1bN1 or pT2N1 without extra-thyroid extension and with nodal largest dimension <2mm pT1aN1 or pT1bN1 or pT2N1 without extra-thyroid extension and with nodal largest dimension >10mm pT2N0/Nx without extra-thyroid extension pT2N1 without extra-thyroid extension and with nodal largest dimension <2mm pT2N1 without extra-thyroid extension and with nodal largest dimension >10mm 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 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

Ages Eligible for Study
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Minimum Age: 18 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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: RAI group<br> | Drug: Systematic RAI-treatment<br>* Administration of 3.7 GBq (100 mCi) or 1,1 GBq (30 mCi) of I131 at the choice of the investigator after rhTSH-stimulation<br>|
| Experimental: GUIDED FOLLOW-UP group<br> | Other: Decision of RAI-treatment guided by a post-operative assessment<br>* The decision-making for the administration of an adapted RAI-treatment will be taken according to the following criteria: No RAI treatment if Tg/LT4 ≤1 ng/mL and rhTSH-sTg ≤10 ng/mL and normal diagnostic RAI-scintigraphy 1.1 GBq after rhTSH if Tg/LT4>1 ng/mL or rhTSH-sTg>10 ng/mL and normal diagnostic RAI-scintigraphy. 3.7 GBq after rhTSH if metastatic lymph-node(s) detected on diagnostic RAI-scintigraphy without distant metastasis 3.7 GBq after hormone withdrawal if distant metastasis detected on diagnostic RAI-scintigraphy or on the hybrid CT scan of the SPECT-CT acquisition<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the rate of patients with excellent tumoral response | normal neck ultrasonography and Tg/LT4 <0.2 ng/mL and absence of TgAb and if performed, no abnormalities on other imaging modalities | 36 months after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient's quality-of-life | Comparison of the scores on SF-36 (score between 0 and 100) between 2 arms | During I131 treatment and at 1 and 3 years | 
| Salivary, nasal and lachrymal toxicities | Comparison of the intensity of salivary, nasal and lachrymal toxicities between 2 arms | During I131 treatment and at 1,2,3 and 5 years | 
| Management cost | Costs of all medical exams and transportation related to the care within 5 years post-randomization in both groups | through study completion, an average of 5 years | 
| Patient's anxiety | Comparison of the scores on STAI questionnaire (score between 20 and 80) between 2 arms | During I131 treatment and at 1 and 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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radioiodine, I131