Comparison of Dosimetry After rhTSH or Withdrawal of Thyroid Hormone in Metastatic or Locally Advanced Thyroid Cancer

Study Overview
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Brief Summary
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Metastases of thyroid cancer with iodine uptake are treated with repeated activity of I-131 administered after thyroid hormone withdrawal. The goal of thyroid hormone withdrawal is to treat patients with elevated thyrotropin stimulated hormone (TSH), a hormone secreted by the pituitary, a gland just located under the brain. Another way to obtain elevated TSH levels is to perform intramuscular injection of recombinant human TSH, a hormone produced pharmaceutically. The goal of this study is to know whether the radioiodine uptake by the metastases is similar after rhTSH administration or after thyroid hormone withdrawal.

Detailed Description
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Patients will undergo a rhTSH stimulation, staying on thyroid hormone treatment. Following 2 administration of rhTSH an injection of I-124 will be performed. Positron emission tomography with computed tomography scans (PET/CT), blood tests, and measurements of whole body radioactivity will occurred during the 4 to 96 hours following I-124 administration in order to perform dosimetry (i.e.) to estimate the radiation dose delivered to the metastases. After 4 weeks under thyroid hormones patients will undergo thyroid hormone withdrawal and a new administration of I-124 will be performed. The same dosimetry study will be realized with PET/CT, blood tests, and measurements of whole body radioactivity. A therapeutic activity of I-131will then be administered followed by whole body scan realized 24 to 72 hours after the administration of I-131. Dosimetry studies will be compared in order to determine whether rhTSH stimulation can replace thyroid hormone withdrawal for the treatment of distant metastases.

Official Title
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Comparison of Dosimetry Following Preparation With Either rhTSH or After Withdrawal of Thyroid Hormone Suppression Therapy in Patients With Metastatic or Locally Advanced Differentiated Thyroid Cancer

Conditions
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Thyroid Cancer, Metastases

Intervention / Treatment
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* Drug: TSH stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with thyroid cancer and known measurable (>1cm) distant metastases demonstrating radioiodine uptake on a previous whole body scan Patients planned for a therapeutic activity of 131I after thyroid hormone withdrawal Age >18 years Previous treatment with radioiodine more than 6 months before inclusion. Serum TSH level <0.5 mU/L Normal renal function with a creatinine clearance estimation using the Cockcroft-Gault formula > 60 ml/ml Effective means of contraception for female patient, at risk of pregnancy Written informed consent Exclusion Criteria: Patients whose majority of tumoral lesions disclose FDG uptake without radioactive iodine uptake Iodine excess (< 50 μg/dl) Large or diffuse bone or brain metastases Patients with multiple small tumor foci less than 1 cm in diameter, such as miliary spread to the lungs Patients already included in a therapeutic trial with an experimental medicine Pregnancy and breast feeding patients Subject with any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures Treatment with antivitamin k

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

Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: TSH stimulation<br>rh TSH stimulation followed by thyroid hormon withdrawal | Drug: TSH stimulation<br>* rh TSH stimulation followed by thyroid hormon withdrawal<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the 124 I uptake after TSH stimulation | For each patient, the 124 I uptake after TSH stimulation (a marker of radiation absorbed dose) will be compared to the uptake after thyroid withdrawal in all lesions (up to 16 lesions per patient maximum). A decrease in the residence time of more than 2.5 fold in 25% or more of the lesions is considered unacceptable. | 4 to 96 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The activity of 131I that should be administered according to each TSH stimulation method | To determine the activity of 131I that should be administered following rhTSH to deliver a radiation absorbed dose similar to that delivered under hypothyroid conditions. A calculated activity above 250mCi is considered unacceptable. | 96 hours | 
| Radiation exposure of the blood | The radiation exposure of the blood, calculated from blood samples and whole body radioactivity measurements | 4 to 96 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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metastatic or locally advanced differentiated thyroid cancer, planned for a therapeutic activity of 131I after thyroid hormone withdrawal