Comparing Complete Remission After Treatment With Selumetinib/Placebo in Patient With Differentiated Thyroid Cancer

Study Overview
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Brief Summary
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The study is designed to evaluate the clinical efficacy, safety and tolerability of selumetinib with radioactive iodine therapy in patients with differentiated thyroid cancer.

Detailed Description
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A Randomised, Double Blind Study to Compare the Complete Remission Rate Following a 5-Week Course of Selumetinib or Placebo and Single Dose Adjuvant Radioactive Iodine Therapy in Patients with Differentiated Thyroid Cancer.

Official Title
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A Randomised, Double Blind Study to Compare the Complete Remission Rate Following a 5-Week Course of Selumetinib or Placebo and Single Dose Adjuvant Radioactive Iodine Therapy in Patients With Differentiated Thyroid Cancer

Conditions
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Differentiated Thyroid Cancer

Intervention / Treatment
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* Drug: Selumetinib
* Drug: Placebo
* Drug: Radioactive Iodine Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Differentiated thyroid cancer Tumor >4 cm, or Gross extra-thyroid extension, or 1 lymph node >1 cm, or 5 or more lymph nodes of any size Previous thyroidectomy Must be able to receive radioactive iodine therapy Must be able to receive Thyroid Stimulating Hormone suppression Exclusion criteria: Metastaic disease Anaplastic thyroid cancer, medullary thyroid cancer or Hurthle cell carcinoma Presence of anti-Tg antibodies Previous treatment with any radiation Unresolved toxicity ≥ common terminology criteria for adverse event Grade 2

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 130 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Selumetinib<br>Selumetinib plus Radioactive Iodine Therapy | Drug: Selumetinib<br>* 3 capsules of 25 mg strength orally twice a day for approximately 5 weeks treatment period<br>Drug: Radioactive Iodine Therapy<br>* A single oral radioactive iodine dose of 100 mCI(3.7 GBq) 131I (+/-10% at the time of administration)to be administered 30 days after randomization. Additionaly, Thyrogen (Recombinant human TSH) will be used to stimulate iodine uptake according to the manufacturer's recommendation(0.9 mg intramuscular injection once a day for the 2 days prior to the dose of radioactive iodine)<br>|
| Placebo Comparator: Placebo<br>Placebo plus Radioactive Iodine Therapy | Drug: Placebo<br>* 3 capsules ( to match Selumetinib capsules) orally twice a day for approximately 5 weeks treatment period<br>Drug: Radioactive Iodine Therapy<br>* A single oral radioactive iodine dose of 100 mCI(3.7 GBq) 131I (+/-10% at the time of administration)to be administered 30 days after randomization. Additionaly, Thyrogen (Recombinant human TSH) will be used to stimulate iodine uptake according to the manufacturer's recommendation(0.9 mg intramuscular injection once a day for the 2 days prior to the dose of radioactive iodine)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Remission Rate (Expressed as Percentage of Patients in Complete Remission) at 18 Months Post-RAI Treatment; ITT Analysis Set | Patients were defined to be in complete remission if all of the following criteria were demonstrated: Serum thyroglobulin (Tg) levels <1 nanograms / millilitre (ng/mL) during rhTSH stimulation, in the absence of interfering Tg antibodies, as assessed by standardised central laboratory analysis. No confirmed evidence of thyroid cancer on neck ultrasound, as assessed by investigator site review. No confirmed radiological evidence of thyroid cancer, as assessed by blinded independent central review. No histopathological evidence of thyroid cancer on fine needle aspiration (FNA)/biopsy when performed, as assessed by investigator site review. No further thyroid cancer therapy was administered in the first 18 months following the initial RAI treatment. | At 18 months post-RAI treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Remission Rate (Expressed as Percentage of Patients in Complete Remission) at 18 Months Post-RAI Treatment; Subgroup Analysis BRAF/NRAS Mutation Positive | Patients were defined to be in complete remission if all of the following criteria were demonstrated: Serum Tg levels <1 ng/mL during rhTSH stimulation, in the absence of interfering Tg antibodies, as assessed by standardised central laboratory analysis. No confirmed evidence of thyroid cancer on neck ultrasound, as assessed by investigator site review. No confirmed radiological evidence of thyroid cancer, as assessed by blinded independent central review. No histopathological evidence of thyroid cancer FNA/biopsy when performed, as assessed by investigator site review. No further thyroid cancer therapy was administered in the first 18 months following the initial RAI treatment. | At 18 months post-RAI treatment | 
| Clinical Remission Rate (Expressed as Percentage of Patients in Clinical Remission) at 18 Months Post-RAI Treatment; ITT Analysis Set | Patients were defined to be in clinical remission if all of the following criteria were demonstrated: Serum Tg levels <1 ng/mL during rhTSH stimulation, in the absence of interfering Tg antibodies, as assessed by standardised central laboratory analysis. No confirmed evidence of thyroid cancer on neck ultrasound, as assessed by investigator site review. No evidence of thyroid cancer on diagnostic whole body scan (WBS), as assessed by blinded independent central review. No histopathological evidence of thyroid cancer on FNA/biopsy when performed to clarify equivocal ultrasound findings, as assessed by investigator site review. No further thyroid cancer therapy was administered in the first 18 months following the initial RAI treatment. | At 18 months post-RAI treatment | 
| Clinical Remission Rate (Expressed as Percentage of Patients in Clinical Remission) at 18 Months Post-RAI Treatment; Subgroup Analysis BRAF/NRAS Mutation Positive | Patients were defined to be in clinical remission if all of the following criteria were demonstrated: Serum Tg levels <1 ng/mL during rhTSH stimulation, in the absence of interfering Tg antibodies, as assessed by standardised central laboratory analysis. No confirmed evidence of thyroid cancer on neck ultrasound, as assessed by investigator site review. No evidence of thyroid cancer on diagnostic WBS, as assessed by blinded independent central review. No histopathological evidence of thyroid cancer on FNA/biopsy when performed to clarify equivocal ultrasound findings, as assessed by investigator site review. No further thyroid cancer therapy was administered in the first 18 months following the initial RAI treatment. | At 18 months post-RAI treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Selumetinib, Differentiated Thyroid Cancer , AZD6244