Treatment with Kinase Inhibitors Plus Myo-Inositol as Re-Differantiating Agents in Iodine Refractory Cancers

Background and aim: Recently pre-clinical studies have confirmed that the inhibition of the MAP kinase pathway can induce re-differentiation of radioiodine refractory(RAIR) follicular-cell thyroid cancers (TC). The aim of this trial is to investigate whether the combination of kinase inhibitors (KIs) with myoinositol (MI) can induce or potentiate the re-uptake of RAI in cancer cells Overview and methods: This is an open label, non-pharmacological, multicenter, randomized pilot study. Patients will be divided into 2 groups: a) a control group in which patients are treated with KIs (T plus D or L); b) a group, in which patients are treated with the same KI and in addition with MI. After 30 days of MI treatment, all patient, treated with L-T4 at a semi-suppressive dosage as per clinical practice, will be stimulated with recombinant human TSH (rhTSH) (days 31 and 32). Then at day 35 patients will be submitted to whole-body scintigraphy, with hybrid imaging where possible (SPECT/TC), after administration of the diagnostic activity (185-222 MBq) of 123-I in accordance with the SNMMI/EANM guidelines. Blood samples will be collected before starting MI therapy (day 0), after 30 days of MI therapy and then at days 31, 32, 33, 34 and 35 after MI therapy. QoL will be assessed at beginning of the MI treatment and at the end of its administration. The primary endpoint is to evaluate the restoration of the 123 uptake in RAIR follicular cell-derived TC patients already on KIs therapy alone and on KIs therapy plus MI. Restoration of the 123 uptake will be evaluated in target lesions. Conclusions: The study evaluates the possible re-differentiation of RAIR cell-derived TC in patients treated with KIs plus MI. The re-uptake of iodine will be evaluated as the primary end point, and Tg values and QoL will be evaluated as the secondary end points. The main limitation of the study is that we do not investigate any clinical effects. We will have to post-pone the clinical analysis to a later date after the administration of RAI for therapeutic purposes.