The selumetinib clinical trial led by Dr. Alan Ho of Memorial Sloan Kettering Cancer Center in New York, NY is now open. The trial evaluates the effectiveness of selumetinib to enhance uptake of radioactive iodine (RAI) for treatment of advanced thyroid cancer. This is a large, multicenter, investigator-initiated, randomized, placebo controlled Phase II trial of selumetinib in patients with RAI-avid, recurrent or metastatic thyroid cancer of follicular cell origin.
Radioiodine is a key therapy for patients with metastatic thyroid cancer of follicular origin, yet many patients have tumors that do not adequately concentrate RAI, leading to diminished clinical effectiveness. Laboratory studies first suggested that aberrant mitogen-activated protein kinase (MAPK) activation suppresses RAI uptake in thyroid cancers, a process that can be reversed with drugs that selectively inhibit this pathway. This observation led ITOG members Dr. Jim Fagin and Dr. Alan Ho to clinically test the idea that blocking MAPK signaling with the MEK1/2 inhibitor selumetinib (AstraZeneca) can restore RAI incorporation in RAI-refractory thyroid cancers. The initial clinical trial of 20 patients established that this approach could enhance RAI uptake and efficacy in a subset of patients. This encouraging work was published in the February 14th, 2013 issue of the New England Journal of Medicine and is the basis for this larger clinical trial of 94 planned patients with RAI-avid disease.
This is ITOG’s second clinical trial and is coordinated by the Academic and Community Cancer Research United (ACCRU). It is funded in part by AstraZeneca as well as generous philanthropy donated to ITOG. To participate, patients must have recurrent and/or metastatic thyroid cancer with at least one tumor that still takes up RAI. Patients who meet all eligibility criteria will be randomized to treatment with selumetinib versus placebo, administered twice daily for 4 weeks. RAI therapy will be given concomitantly with placebo or selumetinib during the fourth week of treatment, after which all therapy is discontinued and patients are monitored for response. Additionally, tumor and blood samples will be analyzed for markers that may predict which patients may benefit from this strategy as well as shed further light on how MAPK signaling contributes to RAI resistance.