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

Phase 3

Terminated

Conditions: Differentiated Thyroid Cancer

Interventions: Drug: Placebo
Drug: Selumetinib
Drug: Radioactive Iodine Therapy

Registration Number: NCT01843062

Lead Sponsor: AstraZeneca

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 233

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

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Selumetinib	Radioactive Iodine Therapy	Selumetinib plus Radioactive Iodine Therapy
Placebo	Placebo	Placebo plus Radioactive Iodine Therapy
Placebo	Radioactive Iodine Therapy	Placebo plus Radioactive Iodine Therapy
Selumetinib	Selumetinib	Selumetinib plus Radioactive Iodine Therapy

Primary Outcome Measures

Name	Time	Method
Complete Remission Rate (Expressed as Percentage of Patients in Complete Remission) at 18 Months Post-RAI Treatment; ITT Analysis Set	At 18 months post-RAI treatment	Patients were defined to be in complete remission if all of the following criteria were demonstrated: 1. 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. 2. No confirmed evidence of thyroid cancer on neck ultrasound, as assessed by investigator site review. 3. No confirmed radiological evidence of thyroid cancer, as assessed by blinded independent central review. 4. No histopathological evidence of thyroid cancer on fine needle aspiration (FNA)/biopsy when performed, as assessed by investigator site review. 5. No further thyroid cancer therapy was administered in the first 18 months following the initial RAI treatment.

Secondary Outcome Measures

Name	Time	Method
Complete Remission Rate (Expressed as Percentage of Patients in Complete Remission) at 18 Months Post-RAI Treatment; Subgroup Analysis BRAF/NRAS Mutation Positive	At 18 months post-RAI treatment	Patients were defined to be in complete remission if all of the following criteria were demonstrated: 1. Serum Tg levels \<1 ng/mL during rhTSH stimulation, in the absence of interfering Tg antibodies, as assessed by standardised central laboratory analysis. 2. No confirmed evidence of thyroid cancer on neck ultrasound, as assessed by investigator site review. 3. No confirmed radiological evidence of thyroid cancer, as assessed by blinded independent central review. 4. No histopathological evidence of thyroid cancer FNA/biopsy when performed, as assessed by investigator site review. 5. No further thyroid cancer therapy was administered in the first 18 months following the initial RAI treatment.
Clinical Remission Rate (Expressed as Percentage of Patients in Clinical Remission) at 18 Months Post-RAI Treatment; ITT Analysis Set	At 18 months post-RAI treatment	Patients were defined to be in clinical remission if all of the following criteria were demonstrated: 1. Serum Tg levels \<1 ng/mL during rhTSH stimulation, in the absence of interfering Tg antibodies, as assessed by standardised central laboratory analysis. 2. No confirmed evidence of thyroid cancer on neck ultrasound, as assessed by investigator site review. 3. No evidence of thyroid cancer on diagnostic whole body scan (WBS), as assessed by blinded independent central review. 4. No histopathological evidence of thyroid cancer on FNA/biopsy when performed to clarify equivocal ultrasound findings, as assessed by investigator site review. 5. No further thyroid cancer therapy was administered in the first 18 months following the initial 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	At 18 months post-RAI treatment	Patients were defined to be in clinical remission if all of the following criteria were demonstrated: 1. Serum Tg levels \<1 ng/mL during rhTSH stimulation, in the absence of interfering Tg antibodies, as assessed by standardised central laboratory analysis. 2. No confirmed evidence of thyroid cancer on neck ultrasound, as assessed by investigator site review. 3. No evidence of thyroid cancer on diagnostic WBS, as assessed by blinded independent central review. 4. No histopathological evidence of thyroid cancer on FNA/biopsy when performed to clarify equivocal ultrasound findings, as assessed by investigator site review. 5. No further thyroid cancer therapy was administered in the first 18 months following the initial RAI treatment.