Comparing Complete Remission After Treatment With Selumet... | NCT01843062

ID	Type	Description	Link
2013-000423-14	EudraCT Number

Status Module

Label	Type	Description	Intervention Names
Selumetinib	Experimental	Selumetinib plus Radioactive Iodine Therapy	Drug: Selumetinib Drug: Radioactive Iodine Therapy
Placebo	Placebo Comparator	Placebo plus Radioactive Iodine Therapy	Drug: Placebo Drug: Radioactive Iodine Therapy

Name	Type	Description	Arm Group Labels	Other Names
Selumetinib	Drug	3 capsules of 25 mg strength orally twice a day for approximately 5 weeks treatment period	Selumetinib

Outcomes Module

Primary Outcomes

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 Outcomes

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.

Eligibility Module

Name	Affiliation	Role
Alan Ho, M.D., PHD	Memorial Sloan Kettering Cancer Centre, 1275 York Avenue, New York, NY 10065.	Principal Investigator
Tracy C Cunningham, M.D	Melbourn Science Park, Cambridge Road, Melbourn, Hertfordshire, SG8 6HB, UK	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Birmingham	Alabama	35233	United States
Research Site

PubMed Identifier	Type	Citation	Retractions
35192411	Derived	Ho AL, Dedecjus M, Wirth LJ, Tuttle RM, Inabnet WB 3rd, Tennvall J, Vaisman F, Bastholt L, Gianoukakis AG, Rodien P, Paschke R, Elisei R, Viola D, So K, Carroll D, Hovey T, Thakre B, Fagin JA; ASTRA investigator group. Selumetinib Plus Adjuvant Radioactive Iodine in Patients With High-Risk Differentiated Thyroid Cancer: A Phase III, Randomized, Placebo-Controlled Trial (ASTRA). J Clin Oncol. 2022 Jun 10;40(17):1870-1878. doi: 10.1200/JCO.21.00714. Epub 2022 Feb 22.

Label	URL
Statistical Analysis Plan-edition 4\_Redacted	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Selumetinib 75 mg BD + RAI	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.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jan 24, 2013	Mar 27, 2019

Arm/Group Information

ID	Title	Description
BG000	Selumetinib 75 mg BD + RAI	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.
BG001	Placebo + 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.
BG002	Total	Total of all reporting groups

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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.

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.

Posted

Number

Percentage of participants

At 18 months post-RAI treatment

ID	Title	Description
OG000	Selumetinib 75 mg BD + RAI	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.
OG001	Placebo + 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.

Units	Counts
Participants	OG000155 OG00178

Title

Denominators

Categories

Title	Measurements
	OG00040.0 OG00138.5

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	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.	Regression, Logistic		0.8205	The primary endpoint was to be considered statistically significant if the 2-sided p-value was less than 0.05. P-value and confidence intervals (CIs) were calculated using profile likelihood.	Odds Ratio (OR)	1.07			2-Sided	95	0.61	1.87					Superiority

Secondary

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.

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.

Posted

Number

Percentage of participants

At 18 months post-RAI treatment

ID	Title	Description
OG000	Selumetinib 75 mg BD + RAI	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.
OG001	Placebo + RAI

Secondary

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.

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.

Posted

Number

Percentage of participants

At 18 months post-RAI treatment

ID	Title	Description
OG000	Selumetinib 75 mg BD + RAI	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.
OG001

Secondary

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.

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.

Posted

Number

Percentage of participants

At 18 months post-RAI treatment

ID	Title	Description
OG000	Selumetinib 75 mg BD + RAI	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.
OG001

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Selumetinib 75 mg BD + RAI	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.	1	155	7	154	141	154
EG001	Placebo + 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.	2	78	0	77	43	77

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Drug hypersensitivity	Immune system disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected154 at risk EG0010 events0 affected77 at risk
Gastric haemorrhage	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected154 at risk EG0010 events0 affected77 at risk
Cellulitis	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected154 at risk EG0010 events0 affected77 at risk
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected154 at risk EG0010 events0 affected77 at risk
Syncope	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected154 at risk EG0010 events0 affected77 at risk
Dermatitis acneiform	Skin and subcutaneous tissue disorders	MedDRA 21.1	Systematic Assessment	EG0002 events2 affected154 at risk EG0010 events0 affected77 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Periorbital oedema	Eye disorders	MedDRA 21.1	Systematic Assessment	EG0008 events8 affected154 at risk EG0010 events0 affected77 at risk
Constipation	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG00015 events15 affected154 at risk EG0013 events3 affected77 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG00078 events68 affected154 at risk EG00113 events12 affected77 at risk
Dry mouth	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG00015 events15 affected154 at risk EG0013 events3 affected77 at risk
Rash follicular	Skin and subcutaneous tissue disorders	MedDRA 21.1	Systematic Assessment	EG00013 events13 affected154 at risk EG0010 events0 affected77 at risk
Dysgeusia	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG0006 events6 affected154 at risk EG0014 events4 affected77 at risk
Rash macular	Skin and subcutaneous tissue disorders	MedDRA 21.1	Systematic Assessment	EG00012 events12 affected154 at risk EG0012 events2 affected77 at risk
Vision blurred	Eye disorders	MedDRA 21.1	Systematic Assessment	EG00016 events16 affected154 at risk EG0015 events5 affected77 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0008 events8 affected154 at risk EG0011 events1 affected77 at risk
Nausea	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG00044 events44 affected154 at risk EG00110 events8 affected77 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG00018 events17 affected154 at risk EG0014 events4 affected77 at risk
Vomiting	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG00014 events14 affected154 at risk EG0010 events0 affected77 at risk
Face oedema	General disorders	MedDRA 21.1	Systematic Assessment	EG0009 events9 affected154 at risk EG0010 events0 affected77 at risk
Fatigue	General disorders	MedDRA 21.1	Systematic Assessment	EG00044 events44 affected154 at risk EG00113 events13 affected77 at risk
Oedema peripheral	General disorders	MedDRA 21.1	Systematic Assessment	EG00032 events30 affected154 at risk EG0014 events4 affected77 at risk
Blood creatine phosphokinase increased	Investigations	MedDRA 21.1	Systematic Assessment	EG00031 events31 affected154 at risk EG0011 events1 affected77 at risk
Weight decreased	Investigations	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected154 at risk EG0014 events4 affected77 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected154 at risk EG0014 events4 affected77 at risk
Headache	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG0008 events8 affected154 at risk EG00111 events10 affected77 at risk
Paraesthesia	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG0004 events4 affected154 at risk EG0014 events4 affected77 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG0003 events3 affected154 at risk EG0014 events4 affected77 at risk
Acne	Skin and subcutaneous tissue disorders	MedDRA 21.1	Systematic Assessment	EG00013 events13 affected154 at risk EG0012 events2 affected77 at risk
Dermatitis acneiform	Skin and subcutaneous tissue disorders	MedDRA 21.1	Systematic Assessment	EG00070 events67 affected154 at risk EG0014 events4 affected77 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 21.1	Systematic Assessment	EG00012 events12 affected154 at risk EG0014 events4 affected77 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 21.1	Systematic Assessment	EG00021 events21 affected154 at risk EG0013 events3 affected77 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA 21.1	Systematic Assessment	EG00019 events19 affected154 at risk EG0014 events4 affected77 at risk
Hypertension	Vascular disorders	MedDRA 21.1	Systematic Assessment	EG00023 events20 affected154 at risk EG0013 events3 affected77 at risk