Drug Repurposing in Thyroid Carcinoma: a Feasibility Trial

This is a phase Ib trial that studies personalized network pharmacology-based drug repurposing in patients with advanced thyroid cancer who have no other treatment options. The main objective is to study if it is feasible to give patients individualized drug combinations selected based on their tumor genetic profile. The secondary objective is to find out whether these treatments are safe and can help control the growth of the patient tumors or stop them from getting worse.

Inclusion Criteria: * Patients with locally advanced or metastatic TC (such as ATC, PDTC, and RAI refractory DTC progressive under treatment with multikinase inhibitors) for whom no approved conventional treatments are available. * Prior anticancer treatment-related toxicities resolved to Grade ≤1 (CTCAE v5.0). * Measurable disease per RECIST 1.1 * ECOG performance status ≤ 2 * Negative pregnancy test within 7 days prior to starting the study in women of childbearing potential and adequate use of contraception. Exclusion Criteria: * Inability to provide informed consent * Inability to obtain a (new) biopsy for molecular profiling * Pregnancy or breastfeeding. * Other active malignancies requiring therapy. * Neutropenia (ANC \< 1.5 × 10⁹/L). * Severe uncontrolled medical conditions (renal, cardiac, liver, respiratory).