Dosimetry-Based Administration of Sodium Iodide (131I) in Metastatic Differentiated Thyroid Cancer: Efficacy and Toxicity Evaluation

The primary objective of this study is to evaluate whether **dosimetry-based** administration of **Sodium Iodide (131I)** can enhance the therapeutic efficacy in patients with metastatic differentiated thyroid cancer (DTC) compared to a fixed activity regimen, while maintaining acceptable levels of toxicity. This is clinically relevant as it aims to optimize treatment outcomes for patients with soft tissue and skeletal metastases, potentially improving survival rates and quality of life.

Secondary objectives include investigating the relationship between the mutational status, gene expression, and variations in miRNA profiles of DTCs before and after therapy, and their association with the refractoriness of lesions to personalized **131I therapy**. Understanding these associations could lead to more tailored and effective treatment strategies for patients with resistant forms of metastatic DTC.

The clinical trial involves participants diagnosed with **metastatic differentiated thyroid cancer (DTC)**, specifically those with soft tissue and skeletal metastasis. The study population includes both male and female subjects aged 18 years and older, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1, indicating they are fully active or restricted in physically strenuous activity but ambulatory. Participants are required to have a life expectancy of more than six months and must demonstrate preserved hematologic and renal function. Females of childbearing potential must have a negative serum pregnancy test prior to registration and agree to use birth control throughout the study and for six months after completion of therapy. The trial does not include a vulnerable population. The sponsor has not provided the total number of participants involved in the study. Participants were selected based on specific inclusion criteria, including a histo-pathological diagnosis of DTC and at least one documented non-surgically-curable soft-tissue metastasis that is previously untreated. Lifestyle considerations such as diet and physical activity are not specified in the available data.

The clinical trial is designed to evaluate the efficacy of **sodium iodide (131I)** administration in patients with metastatic differentiated thyroid cancer (DTC). The study employs a randomized, double-blind, controlled trial design to ensure the reliability and validity of the results. The trial is expected to span approximately four years, with an estimated end date of March 15, 2025. Participants will be involved in the study for a maximum treatment period of 48 weeks, during which they will receive up to two administrations of the investigational product, optimized with personalized pre-treatment dosimetry based on 124I-PET/CT.

The sequence of study visits begins with an inclusion (screening) visit, where eligibility criteria are assessed, including a histo-pathological diagnosis of DTC, documented non-surgically-curable soft-tissue metastasis, and an ECOG performance status of 0-1. Participants must be at least 18 years old, with a life expectancy greater than six months, and must provide signed informed consent. Females of childbearing age are required to have a negative serum pregnancy test and agree to use birth control throughout the study and for six months after therapy completion. Follow-up visits will occur at regular intervals to monitor treatment response and assess any adverse events. The primary endpoint is the evaluation of the complete response rate on soft tissue metastases six months after the last optimized administration. Secondary endpoints include the assessment of acute toxicity rate and severity, as well as the association between genetic mutations, miRNA expression, glucose metabolism, iodine uptake, and therapy response.

The end-of-study visit will involve a comprehensive evaluation of the participant's response to treatment, using a combination of RECIST, 124I-PET/CT, 18F-FDG, and thyroglobulin assessments. Participants may be terminated early from the study if they experience unacceptable toxicity, withdraw consent, or if the investigator deems it in the participant's best interest. The trial aims to provide insights into the potential benefits of dosimetry-based 131I administration in improving treatment outcomes for patients with metastatic DTC.

The clinical trial involves the administration of **Sodium Iodide (131I)**, marketed as "Sodio ioduro (I131) Curium Netherlands 37-7400 MBq capsula rigida." This experimental medication is provided in the form of a hard capsule, intended for **oral** administration. The active substance, **Sodium Iodide (131I)**, is of chemical origin and is utilized for its therapeutic properties in the treatment of metastatic thyroid cancer. The maximum daily dose is set at 800 MBq, with a total maximum dose of 60,000 MBq over a treatment period not exceeding 48 weeks. The dosing schedule is determined based on dosimetry to optimize efficacy while maintaining acceptable toxicity levels. Participant compliance is monitored through regular assessments and adherence checks.

In addition to the experimental treatment, a non-experimental radiotracer is used in the study. This radiotracer is classified under the ATC code V09F, associated with thyroid imaging. The pharmaceutical form is denoted as PHF00006MIG, and it is also administered orally. The maximum daily and total dose for this radiotracer is 100 MBq/ml, with a treatment period of up to 48 weeks. The radiotracer serves as a comparator to evaluate the effectiveness of the dosimetry-based administration of **Sodium Iodide (131I)**. Compliance with the administration of the radiotracer is similarly monitored to ensure accurate study results.

Efficacy in this clinical trial will be assessed through the evaluation of the **complete response (CR) rate** on soft tissue metastases in patients with differentiated thyroid cancer (DTC). This assessment will occur after a maximum of two administrations of radioiodine, optimized with personalized pre-treatment dosimetry based on 124I-PET/CT. The response will be evaluated six months following the last optimized administration. The evaluation will be a combination of several assessments, including RECIST criteria, 124I-PET/CT imaging, 18F-FDG uptake, and thyroglobulin levels.

Secondary endpoints include the assessment of acute toxicity rate and severity, as well as the investigation of associations among pre-treatment glucose metabolism, 124I uptake, and therapy response. Additionally, the trial will assess the relationship between genetic mutations in cancer tissue, pre- and post-treatment miRNA expression, pre- and post-treatment glucose metabolism, iodine uptake, and the response to 131I therapy. These parameters will be measured and analyzed using appropriate laboratory tests and imaging techniques at specified timepoints throughout the study.