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Table 1 Eligibility criteria

From: Investigating the potential clinical benefit of Selumetinib in resensitising advanced iodine refractory differentiated thyroid cancer to radioiodine therapy (SEL-I-METRY): protocol for a multicentre UK single arm phase II trial

Inclusion Criteria
 - Diagnosed with locally advanced or metastatic differentiated thyroid cancer (papillary, follicular, Hürthle cell, or poorly differentiated carcinoma) with at least one measurable lesion as measured by computed tomography (CT) or magnetic resonance imaging (MRI)
 - Participants must have iodine refractory disease defined by one or more of the following:
  • One or more measurable lesions that do not demonstrate iodine uptake on a previous radioiodine scan (diagnostic uptake or post therapy)
  OR
  • One or more measurable lesions that have progressed by RECIST 1.1 criteria within 12 months of I-131 therapy, despite demonstrable radioiodine avidity at the time of that treatment
 - Participants must have radiological progression by RECIST 1.1 criteria within the prior 12 months
 - Measurable disease by RECIST 1.1 criteria. Baseline scan must be completed within 4 weeks prior to the start of treatment.
 - ECOG Performance Status ≤1 and able to tolerate radioiodine therapy
 - Life expectancy of at least 12 weeks
 - Required laboratory values within 14 days of day 1 of treatment:
  • Adequate thyroid-stimulating hormone (TSH) suppression < 0.5 mU/L
  • Creatinine clearance > 50 ml/min
  • Absolute Neutrophil Count ≥1.5 × 109/L (1500 per mm3)
  • Platelets ≥100 × 109/L (100,000 per mm3)
  • Haemoglobin > 9.0 g/dL
  • Serum bilirubin ≤1.5 x upper limit of normal (ULN)
  • Patients with no liver metastasis must have AST or ALT ≤2.5 x ULN
  • Patients with liver metastasis must have AST or ALT ≤5 x ULN. If patients have AST or ALT > 3.5 x ULN and ≤ 5 x ULN they must have an ALP ≤ 6 x ULN
 - Able to give informed consent and willing to follow trial protocol.
 - Aged over 18 years or over
 - Female participants of child-bearing potential must have a negative pregnancy test within 24 h prior to starting therapy and agree to use dual methods of contraception for the duration of the trial and 6 months after completing treatment. Male participants must agree to use a barrier method of contraception for the duration of the trial and 4 months after completing treatment, if sexually active with a female of child-bearing potential.
 - Able to swallow Selumetinib/I-131 capsules whole
Exclusion criteria
 - Foci of anaplastic thyroid cancer
 - Able to receive curative surgery or radiation therapy
 - Major surgery (with the exception of surgical placement for vascular access), open biopsy, or significant traumatic injury ≤30 days prior to registration
 - Previous or concurrent cancer distinct in primary site or histology from thyroid cancer within previous 5 years, except for cervical cancer in situ, treated basal cell carcinoma, or squamous cell carcinoma of the skin or superficial bladder tumour
 - Have received or are receiving an IMP or other systemic anticancer treatment within 4 weeks prior to the first dose of study treatment (6 weeks for nitrosoureas, mitomycin, and suramin), or within a period during which the IMP or anticancer treatment has not been cleared from the body (e.g. a period of 5 ‘half-lives’), whichever is the most appropriate and as judged by the investigator
 - Any unresolved toxicity ≥CTCAE Grade 2 from previous anti-cancer therapy, except for alopecia
 - Prior exposure to Tyrosine Kinase, MEK, RAS or RAF inhibitors
 - Known or suspected allergy to Selumetinib or hypersensitivity to Selumetinib or any excipient agents or history of allergic reactions attributed to compounds of similar chemical or biologic composition to Selumetinib
 - Have known or suspected brain metastases or spinal cord compression, unless the condition has been asymptomatic, has been treated with surgery and / or radiation, and has been stable without requiring corticosteroids nor anti-convulsant medications for at least 4 weeks prior to the first dose of study medication.
 - Requiring medication with high iodine content (e.g. amiodarone)
 - Participants who have had a Iodine contrast enhanced CT scan in previous 2 months
 - Ophthalmological conditions as follows:
  • Intra-ocular pressure > 21 mmHg, or uncontrolled glaucoma (irrespective of intra-ocular pressure)
  • Current or past history of retinal pigment epithelial detachment (REPD)/central serous retinopathy or retinal vein occlusion
 - Any of the following cardiac conditions
  • Uncontrolled hypertension (BP ≥150/95 mmHg despite medical therapy)
  • Acute coronary syndrome within 6 months prior to starting treatment
  • Uncontrolled angina (Canadian Cardiovascular Society grade II-IV despite medical therapy)
  • Symptomatic heart failure (NYHA grade II-IV), prior or current cardiomyopathy, or severe valvular heart disease
  • Prior or current cardiomyopathy including but not limited to the following:
  • Known hypertrophic cardiomyopathy
  • Known arrhythmogenic right ventricular cardiomyopathy
  • Severe valvular heart disease
  • Left ventricular ejection fraction < 55% measured by echocardiography
  • Atrial fibrillation with a ventricular rate > 100 bpm on ECG at rest
  • QTcF > 450 ms or other factors that increase the risk of QT prolongation
 - Participants known to be infected with human immunodeficiency virus (HIV) or hepatitis B (HBV) or C (HCV) virus
 - Any evidence of severe or uncontrolled systemic disease (e.g. unstable or uncompensated respiratory, cardiac, hepatic, or renal disease), active infection, active bleeding (including hepatitis B, hepatitis C, HIV), diatheses or renal transplant.
 - Pregnant or breastfeeding females
 - Male or female patients of reproductive potential and, as judged by the investigator, are not employing an effective method of birth control
 - Have evidence of any other significant clinical disorder or laboratory finding that, as judged by the investigator, makes it undesirable for the patient to participate in the study.
 - Hypersensitivity to bovine or human thyroid stimulating hormone or to any of the following excipients; mannitol, sodium phosphate monobasic, monohydrate, sodium phosphate dibasic, heptahydrate or sodium chloride.
 - Hypersensitivity to I-123 or I-131 or to any of the following excipients; acetic acid, sodium hydroxide, sodium thiosulphate, sodium bicarbonate, sodium chloride, disodium phosphate anhydrous or silica
 - Patients with dysphagia, oesophageal stricture, active gastritis, gastric erosions and peptic ulcer.
 - Have refractory nausea and vomiting, chronic gastrointestinal diseases (e.g., inflammatory bowel disease), suspected reduced gastrointestinal motility or significant bowel resection that would adversely affect the absorption/bioavailability of orally administered study medication.