A Study to Try to Bring Back Radioiodine Sensitivity in Patients With Advanced Thyroid Cancer.

Thyroid cancers that have spread beyond the neck are not curable. About 30,000 people worldwide die from thyroid cancer every year. Usually, thyroid cancers get worse because the cancer cells become more and more abnormal through a process that is called dedifferentiation. Radioactive iodine is a standard treatment for this type of thyroid cancer. Patients will usually receive multiple dose of radioactive iodine over the course of their cancer journey. Thyroid cancers lose sensitivity to radioactive iodine as the cancer progresses/worsens with the process of dedifferentiation. When this occurs, the radioactive iodine treatments no longer work against the cancer and the cancer grows. Radioactive iodine enters cancer cells through transporter proteins on the outside of the cancer cell. The transporter proteins that are the most important are the sodium iodide symporters. As thyroid cancers dedifferentiate, these symporters stop working as well as they once did. The radioactive iodine can therefore not get into the cancer cells to cause cancer cell death. Laboratory research has shown that in thyroid cancer, a protein on the cell called platelet derived growth factor receptor alpha (PDGFRα) is an important for tumour growth and thyroid cancer dedifferentiation. PDGFRα helps cancer progression and lowers the ability of sodium iodine symporters to move radioiodine into cells where it would normal act to kill the cancer cells. PDGFRα therefore makes thyroid cells resistant to radioactive iodine. Imatinib is an anti-cancer drug that blocks PDGFRα function. It has been used for many years to treat other cancers such as leukemia. The investigators who wrote this study believe that, base on laboratory testing, if thyroid cancer patients are given imatinib whenafter their cancers have become resistant to radioactive iodine, the imatinib will block PDGFRα. This will let the sodium iodine symporters work again and move the radioactive iodine into the cancer cells. This should shrink the tumours. Imatinib would then make the thyroid cancer cell sensitive to radioactive iodine again. This should shrink the tumours and would mean longer control of the cancer, helping people with this disease live longer.

This proposed new method of therapy for patients with progressive, metastatic papillary or follicular thyroid cancers will combine a focused blockade of PDGFRα with radioactive iodine. This is based on a new model for dedifferentiation in thyroid cancer as recently published by Lopez-Campistrous et al., 2016 (Appendix 1). Using this model and extensive preclinical data, the investigators hypothesize that the relatively short course of the well-known drug imatinib will allow for re-differentiation of thyroid cancers permitting radioactive iodine transport thus restoring sensitivity to radioactive iodine. The efficacy of these agents will be determined in a trial of 18 patients through a short treatment phase of approximately 3 months through which the investigators should be able to determine a clinically relevant response. The investigators believe this trial is highly clinically relevant and has the benefits of using previously well described treatments in a novel pattern that should maximize efficacy while minimizing toxicity. If successful, this trial will translate into a new treatment paradigm for metastatic thyroid cancer.