Abstract
BackgroundThyroid cancer is the most common endocrine malignancy. Some advanced disease is, or becomes, resistant to radioactive iodine therapy (refractory disease); this holds poor prognosis of 10% 10-year overall survival. Whilst Sorafenib and Lenvatinib are now licenced for the treatment of progressive iodine refractory thyroid cancer, these treatments require continuing treatment and can be associated with significant toxicity.Evidence from a pilot study has demonstrated feasibility of Selumetinib to allow the reintroduction of I-131 therapy; this larger, multicentre study is required to demonstrate the broader clinical impact of this approach before progression to a confirmatory trial.MethodsSEL-I-METRY is a UK, single-arm, multi-centre, two-stage phase II trial. Participants with locally advanced or metastatic differentiated thyroid cancer with at least one measureable lesion and iodine refractory disease will be recruited from eight NHS Hospitals and treated with four-weeks of oral Selumetinib and assessed for sufficient I-123 uptake (defined as any uptake in a lesion with no previous uptake or 30% or greater increase in uptake). Those with sufficient uptake will be treated with I-131 and followed for clinical outcomes. Radiation absorbed doses will be predicted from I-123 SPECT/CT and verified from scans following the therapy. Sixty patients will be recruited to assess the primary objective of whether the treatment schedule leads to increased progression-free survival compared to historical control data.DiscussionThe SEL-I-METRY trial will investigate the effect of Selumetinib followed by I-131 therapy on progression-free survival in radioiodine refractory patients with differentiated thyroid cancer showing increased radioiodine uptake following initial treatment with Selumetinib. In addition, information on toxicity and dosimetry will be collected. This study presents an unprecedented opportunity to investigate the role of lesional dosimetry in molecular radiotherapy, leading to greater personalisation of therapy. To date this has been a neglected area of research. The findings of this trial will be useful to healthcare professionals and patients alike to determine whether further study of this agent is warranted. It is hoped that the development of the infrastructure to deliver a multicentre trial involving molecular radiotherapy dosimetry will lead to further trials in this field.Trial registrationSEL-I-METRY is registered under ISRCTN17468602, 02/12/2015.
Highlights
Thyroid cancer is the most common endocrine malignancy
The SEL-I-METRY trial will investigate the effect of Selumetinib followed by I-131 therapy on progression-free survival in radioiodine refractory patients with differentiated thyroid cancer showing increased radioiodine uptake following initial treatment with Selumetinib
This study presents an unprecedented opportunity to investigate the role of lesional dosimetry in molecular radiotherapy, leading to greater personalisation of therapy
Summary
Design SEL-I-METRY is a UK, single arm, multi-centre, twostage phase II proof of concept trial investigating the use of Selumetinib to resensitise iodine refractory patients with differentiated thyroid cancer. Secondary endpoints Safety: Serious adverse events (SAEs) from registration until 30 days post cessation of trial therapy (Selumetinib or I-131 therapy); suspected unexpected serious adverse reactions (SUSARs) and serious adverse reaction (SARs) recorded for all from start of protocol treatment for the lifetime of the trial; Toxicity: Adverse reactions (ARs) as graded by common terminology criteria for adverse events (CTCAE) v4.0; Overall survival (OS): calculated from date of registration to date of death; censoring will occur at last known date alive for those alive at time of analysis; Sufficient iodine uptake: reviewed centrally; sufficient uptake is defined as presence of any clinically relevant uptake in a lesion in which there was previously no uptake or an increase of 30% or more in uptake in a lesion with evidence of some uptake on the baseline scan; Radiological response: assessed via CT scans and based on response evaluation criteria in solid tumours (RECIST) v1.1. The DMEC may request that the trial be terminated for lack of activity if there is evidence to suggest that 12 month PFS is no better than 25% based on the Nelson-Aalen estimator
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
