Neoplasms

Gland and Hormone Related Diseases

All Conditions

Thyroid Neoplasms

Thyroid Diseases

Endocrine System Diseases

Endocrine Gland Neoplasms

Head and Neck Neoplasms

Micronutrients

Anti-Infective Agents

All Drugs and Chemicals

Iodine

Cadexomer iodine

Selumetinib plus Radioactive Iodine Therapy

3 capsules of 25 mg strength orally twice a day for approximately 5 weeks treatment period

Selumetinib

3 capsules ( to match Selumetinib capsules) orally twice a day for approximately 5 weeks treatment period

Placebo

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)

Radioactive Iodine Therapy

Alan Ho, M.D., PHD

Tracy C Cunningham, M.D

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

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.

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

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

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.

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.

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.

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.

AstraZeneca

All-Cause Mortality is reported for the ITT analysis set for the overall study period. Serious and Other (non-serious) AE data is reported for the safety analysis set (including all patients who received at least 1 dose of randomised treatment) for the 5-week treatment period plus 30-day follow-up phase.

Patients received selumetinib (75 mg, orally BD), for a period of approximately 5 weeks. Selumetinib was to be started approximately 4 weeks prior to the planned day of RAI therapy administered as a single oral dose of 100 mCi. To stimulate iodide uptake, patients received a rhTSH injection for each of the 2 days immediately prior to RAI therapy.

Selumetinib 75 mg BD + RAI

Patients received placebo capsules (to match selumetinib, orally BD), for a period of approximately 5 weeks. Placebo was to be started approximately 4 weeks prior to the planned day of RAI therapy administered as a single oral dose of 100 mCi. To stimulate iodide uptake, patients received a rhTSH injection for each of the 2 days immediately prior to RAI therapy.

Placebo + RAI

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race/Ethnicity, Customized

The ITT analysis set included all randomised patients. Patients who were randomised but did not subsequently go on to receive selumetinib/placebo were included in the ITT analysis set.

The study was terminated early (based on the findings of the primary analysis at 18 months post-RAI treatment) and all randomised patients who had not yet completed their 3-year follow-up visit were instead to have an end of study phone call.

Global Clinical Lead

Selumetinib in combination with RAI was compared with placebo in combination with RAI. The analysis was performed using a logistic regression model including treatment as the only covariate. An odds ratio \>1 favours selumetinib in combination with RAI.

Complete Remission Rate (Expressed as Percentage of Patients in Complete Remission) at 18 Months Post-RAI Treatment; ITT Analysis Set

The BRAF/NRAS mutation positive analysis set included only those patients from the ITT population whose tumour samples were mutation positive for the oncogenes BRAF or NRAS.

Complete Remission Rate (Expressed as Percentage of Patients in Complete Remission) at 18 Months Post-RAI Treatment; Subgroup Analysis BRAF/NRAS Mutation Positive

Clinical Remission Rate (Expressed as Percentage of Patients in Clinical Remission) at 18 Months Post-RAI Treatment; ITT Analysis Set

Clinical Remission Rate (Expressed as Percentage of Patients in Clinical Remission) at 18 Months Post-RAI Treatment; Subgroup Analysis BRAF/NRAS Mutation Positive

Patients received selumetinib (75 milligrams \[mg\], orally twice daily \[BD\]), for a period of approximately 5 weeks. Selumetinib was to be started approximately 4 weeks prior to the planned day of RAI therapy administered as a single oral dose of 100 millicuries (mCi). To stimulate iodide uptake, patients received a recombinant human thyroid stimulating hormone (rhTSH) injection for each of the 2 days immediately prior to RAI therapy.

Spots Global Cancer Trial Database for selumetinib, differentiated thyroid cancer , azd6244