Iodine-refractory thyroid cancer of papillary, follicular, Hürthle cell or poorly differentiated carcinoma MedDRA version: 18.0 Level: PT Classification code 10071029 Term: Thyroid cancer stage III System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 18.0 Level: PT Classification code 10016935 Term: Follicular thyroid cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA ve
Conditions
Interventions
Product Name: Selumetinib
Product Code: AZD6244
Pharmaceutical Form: Capsule
INN or Proposed INN: Selumetinib
CAS Number: 606143-52-6
Concentration unit: mg milligram(s)
Concentration type: equal
Conc
Sponsors
Sheffield Teaching Hospitals NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
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: o Adequate thyroid-stimulating hormone (TSH) suppression 50 ml/min, o Absolute Neutrophil Count =1.5x109/L (1500 per mm3) o Platelets =100x109/L (100,000 per mm3) o Haemoglobin >9.0 g/dL o Serum bilirubin =1.5 x upper limit of normal (ULN) o Patients with no liver metastasis must have AST or ALT = 2.5 x ULN o 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 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
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: o Intra-ocular pressure >21 mmHg, or uncontrolled glaucoma (irrespective of intra-ocular pressure) o Current or past history of retinal pigment epithelial detachment (REPD)/central serous retinopathy or retinal vein occlusion • Any of the following cardiac conditions o Uncontrolled hypertension (BP =150/95 mmHg despite medical therapy) o Acute coronary syndrome within 6 months prior to starting treatment o Uncontrolled angina (Canadian Cardiovascular Society grade II-IV despite medical therapy) o Symptomatic heart failure (NYHA grade II-IV), prior or current cardiomyopathy, or severe valvular heart disease o Prior or current cardiomyopathy including but not limited to the following: ? Known hypertrophic cardiomyopathy ? Known arrhythmogenic right ventricular cardiomyopathy o Severe valvular heart disease o Left ventricular ejection fraction 100 bpm on ECG at rest o QTcF >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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of Selumetinib followed by radioiodine therapy in iodine refractory patients with differentiated thyroid cancer demonstrating increased iodine uptake following initial treatment with Selumetinib. The principal objective is to determine whether this schedule may lead to increased progression-free survival compared to historical control data. ;Secondary Objective: To assess the safety and toxicity of Selumetinib To assess efficacy based on response and overall survival to Selumetinib followed by radioiodine therapy To determine the rate of iodine uptake in metastatic lesions in iodine refractory patients with differentiated thyroid cancer treated with Selumetinib. ;Timepoint(s) of evaluation of this end point: This primary outcome will be evaluated 12 months following inclusion into the study.;Primary end point(s): The primary endpoint for this trial is progression free survival at 12 months in patients with iodine-refractory thyroid cancer. Progression-free survival is calculated from the date of registration to first documented evidence of disease progression or death. Participants who have not progressed at the time of analysis will be censored at the last date they were known to be alive and progression-free. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints of this study are: To assess the safety and toxicity of selumetinib - toxicity will be reported based on adverse reactions, as graded by CTCAE V4.0, and determined by routine clinical assessments at each centre. Safety will be reported based on the occurrence of SAEs, SARs and SUSARs. To assess the radiological response rate for patients receiving radioiodine therapy - this will be assessed via 3 monthly CT scans for the first 12 months, 6 monthly thereafter, and will be based on RECIST v1.1 To assess the overall survival - calculated from the date of registration to death. Patients who are still alive at the time of analysis will be censored at the last date they were known to be alive. To assess the proportion of patients with sufficient iodine uptake to warrant radioiodine therapy. ;Timepoint(s) of evaluation of this end point: These endpoints will be assessed: To assess the safety and toxicity of selumetinib - ongoing assessment. To assess the radiological response rate for patients receiving radioiodine therapy - following radioiodine therapy if achieved, 3-monthly for first 12 months then 6-monthly. To assess the overall survival - ongoing assessment To assess the proportion of patients with sufficient iodine uptake to warrant radioiodine therapy - at the end of selumetinib therapy | — |
Countries
United Kingdom
Contacts
Public ContactLICTR
Leeds Institute of Clinical Trials Research
Outcome results
None listed