Investigating the potential clinical benefit of Selumetinib in re-sensitising advanced iodine refractory differentiated thyroid cancer to radioiodine therapy.

• Conditions: Iodine-refractory thyroid cancer of papillary, follicular, Hürthle cell or poorly differentiated carcinoma; MedDRA version: 18.0Level: PTClassification code 10071029Term: Thyroid cancer stage IIISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 18.0Level: PTClassification code 10016935Term: Follicular thyroid cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 18.0Level: PTClassification code 10071030Term: Thyroid cancer stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 18.0Level: PTClassification code 10066474Term: Thyroid cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 18.0Level: PTClassification code 10055107Term: Thyroid cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 18.0Level: PTClassification code 10033701Term: Papillary thyroid cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2015-002269-47-GB
• Lead Sponsor: Sheffield Teaching Hospitals NHS Foundation Trust

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2015-09-28
• Last Update Posted: 25 April 2016

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 60

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 below:
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.
•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:
oAdequate thyroid-stimulating hormone (TSH) suppression < 0.5 mU/L
oCreatinine clearance >50 ml/min,
oAbsolute Neutrophil Count =1.5x109/L (1500 per mm3)
oPlatelets =100x109/L (100,000 per mm3)
oHaemoglobin >9.0 g/dL
oSerum bilirubin =1.5 x upper limit of normal (ULN)
oPatients with no liver metastasis must have AST or ALT = 2.5 x ULN
oPatients 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
Patient’s with Gilbert’s syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of evidence of haemolysis or hepatic pathology) will be eligible.
•Able to give informed consent and willing to follow trial protocol.
•Aged over 18
•Female participants of child-bearing potential must have a negative pregnancy test within 24 hours 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.

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 30
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30

Exclusion Criteria

•Foci of anaplastic thyroid cancer identified on histology
•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, 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 Selumentinib or hypersensitivity to Selumetinib or any excipient agents or history of allergic reactions attributed to compounds of similar chemical or biologic composition to Selumetinib
•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 iIodine contrast enhanced CT scan in previous 2 months

•Ophthalmological conditions as follows:
oIntra-ocular pressure >21 mmHg, or uncontrolled glaucoma (irrespective of intra-ocular pressure)
oCurrent or past history of retinal pigment epithelial detachment (REPD)/central serous retinopathy or retinal vein occlusion
•Any of the following cardiac conditions
oUncontrolled hypertension (BP =150/95 mmHg despite medical therapy)
oAcute coronary syndrome within 6 months prior to starting treatment
oUncontrolled angina (Canadian Cardiovascular Society grade II-IV despite medical therapy)
oSymptomatic heart failure (NYHA grade II-IV), prior or current cardiomyopathy, or severe valvular heart disease
oPrior or current cardiomyopathy including but not limited to the following:
?Known hypertrophic cardiomyopathy
?Known arrhythmogenic right ventricular cardiomyopathy
oSevere valvular heart disease
oLeft ventricular ejection fraction <55% measured by echocardiography
oAtrial fibrillation with a ventricular rate >100 bpm on ECG at rest
oQTcF >450ms or other factors that increase the risk of QT prolongation
•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(including hepatitis B, hepatitis C, HIV), active bleeding diatheses or renal transplant
•Pregnant or breastfeeding females
•Male or female patients of reproductive potential who 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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified