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

Sponsor
AstraZeneca (Industry)
Overall Status
Terminated
CT.gov ID
NCT01843062
Collaborator
(none)
233
45
2
66.3
5.2
0.1

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 3

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
233 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
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
Actual Study Start Date :
Aug 27, 2013
Actual Primary Completion Date :
May 18, 2018
Actual Study Completion Date :
Mar 6, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: Selumetinib

Selumetinib plus Radioactive Iodine Therapy

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

Drug: Radioactive Iodine Therapy
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)

Placebo Comparator: Placebo

Placebo plus Radioactive Iodine Therapy

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

Drug: Radioactive Iodine Therapy
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)

Outcome Measures

Primary Outcome Measures

  1. 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: 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.

Secondary Outcome Measures

  1. 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: 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.

  2. 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: 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.

  3. 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: 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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 130 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Research Site Birmingham Alabama United States 35233
2 Research Site Little Rock Arkansas United States 72205
3 Research Site Los Angeles California United States 90048
4 Research Site Torrance California United States 90502
5 Research Site Aurora Colorado United States 80045
6 Research Site Washington District of Columbia United States 20010
7 Research Site Boston Massachusetts United States 02114
8 Research Site Boston Massachusetts United States 02215
9 Research Site New York New York United States 10029
10 Research Site New York New York United States 10065
11 Research Site Durham North Carolina United States 27710
12 Research Site Cincinnati Ohio United States 45219
13 Research Site Portland Oregon United States 97239
14 Research Site Philadelphia Pennsylvania United States 19014
15 Research Site Nashville Tennessee United States 37232-8148
16 Research Site Barretos Brazil 14784-400
17 Research Site Porto Alegre Brazil
18 Research Site Ribeirão Preto Brazil
19 Research Site Rio de Janeiro Brazil
20 Research Site São José do Rio Preto Brazil
21 Research Site São Paulo Brazil
22 Research Site Odense C Denmark 5000
23 Research Site Angers Cedex 01 France 49033
24 Research Site Bordeaux Cedex France 33076
25 Research Site Caen Cedex 5 France 41076
26 Research Site Lyon France
27 Research Site Toulouse Cedex 9 France 31059
28 Research Site Villejuif Cedex France 94805
29 Research Site Augsburg Germany 86156
30 Research Site Essen Germany 45122
31 Research Site Leipzig Germany 04103
32 Research Site Catania Italy 95122
33 Research Site Napoli Italy 80131
34 Research Site Pisa Italy 56124
35 Research Site Roma Italy 00161
36 Research Site Gliwice Poland 44-101
37 Research Site Kielce Poland 25-734
38 Research Site Poznań Poland 60-355
39 Research Site Warszawa Poland 02-507
40 Research Site Warszawa Poland 02-781
41 Research Site Zgierz Poland 95-100
42 Research Site Göteborg Sweden 413 45
43 Research Site Linköping Sweden 581 85
44 Research Site Lund Sweden 221 85
45 Research Site Stockholm Sweden 171 76

Sponsors and Collaborators

  • AstraZeneca

Investigators

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

Study Documents (Full-Text)

More Information

Additional Information:

Publications

None provided.
Responsible Party:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01843062
Other Study ID Numbers:
  • D1532C00065
  • 2013-000423-14
First Posted:
Apr 30, 2013
Last Update Posted:
Aug 28, 2019
Last Verified:
Aug 1, 2019
Keywords provided by AstraZeneca
Additional relevant MeSH terms:

Study Results

Participant Flow

Recruitment Details Study conducted between 27 Aug 2013 and 06 Mar 2019. 42 centres in 8 countries randomised patients in the study. A primary analysis was performed for the 18 months post-radioactive iodine (RAI) treatment period with a data cut-off of 18 May 2018. All primary and secondary outcome measures were reported at the time of the primary analysis.
Pre-assignment Detail Eligible patients with differentiated thyroid cancer at high risk of primary treatment failure were randomly assigned (ratio 2:1), to receive selumetinib in combination with adjuvant RAI therapy or placebo and adjuvant RAI therapy for a period of approximately 5 weeks.
Arm/Group Title Selumetinib 75 mg BD + RAI Placebo + RAI
Arm/Group Description 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. 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.
Period Title: Overall Study
STARTED 155 78
Intention to Treat (ITT) Analysis Set 155 78
Safety Analysis Set 154 77
BRAF/NRAS Mutation Positive Analysis Set 91 51
Ongoing at Primary Analysis Data Cut-off 134 71
COMPLETED 133 69
NOT COMPLETED 22 9

Baseline Characteristics

Arm/Group Title Selumetinib 75 mg BD + RAI Placebo + RAI Total
Arm/Group Description 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. 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. Total of all reporting groups
Overall Participants 155 78 233
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]
46.2
(14.20)
47.9
(14.67)
46.8
(14.35)
Sex: Female, Male (Count of Participants)
Female
92
59.4%
40
51.3%
132
56.7%
Male
63
40.6%
38
48.7%
101
43.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino
27
17.4%
14
17.9%
41
17.6%
Not Hispanic or Latino
128
82.6%
64
82.1%
192
82.4%
Unknown or Not Reported
0
0%
0
0%
0
0%
Race/Ethnicity, Customized (Count of Participants)
White
145
93.5%
73
93.6%
218
93.6%
Black or African American
3
1.9%
1
1.3%
4
1.7%
Asian
3
1.9%
3
3.8%
6
2.6%
Other
4
2.6%
1
1.3%
5
2.1%

Outcome Measures

1. Primary Outcome
Title Complete Remission Rate (Expressed as Percentage of Patients in Complete Remission) at 18 Months Post-RAI Treatment; ITT Analysis Set
Description 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.
Time Frame At 18 months post-RAI treatment

Outcome Measure Data

Analysis Population Description
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.
Arm/Group Title Selumetinib 75 mg BD + RAI Placebo + RAI
Arm/Group Description 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. 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.
Measure Participants 155 78
Number [Percentage of participants]
40.0
25.8%
38.5
49.4%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Selumetinib 75 mg BD + RAI, Placebo + RAI
Comments 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.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.8205
Comments 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.
Method Regression, Logistic
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.07
Confidence Interval (2-Sided) 95%
0.61 to 1.87
Parameter Dispersion Type:
Value:
Estimation Comments
2. Secondary Outcome
Title Complete Remission Rate (Expressed as Percentage of Patients in Complete Remission) at 18 Months Post-RAI Treatment; Subgroup Analysis BRAF/NRAS Mutation Positive
Description 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.
Time Frame At 18 months post-RAI treatment

Outcome Measure Data

Analysis Population Description
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.
Arm/Group Title Selumetinib 75 mg BD + RAI Placebo + RAI
Arm/Group Description 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. 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.
Measure Participants 91 51
Number [Percentage of participants]
37.4
24.1%
41.2
52.8%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Selumetinib 75 mg BD + RAI, Placebo + RAI
Comments 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.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.6549
Comments P-value and CIs were calculated using profile likelihood.
Method Regression, Logistic
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.85
Confidence Interval (2-Sided) 95%
0.42 to 1.73
Parameter Dispersion Type:
Value:
Estimation Comments
3. Secondary Outcome
Title Clinical Remission Rate (Expressed as Percentage of Patients in Clinical Remission) at 18 Months Post-RAI Treatment; ITT Analysis Set
Description 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.
Time Frame At 18 months post-RAI treatment

Outcome Measure Data

Analysis Population Description
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.
Arm/Group Title Selumetinib 75 mg BD + RAI Placebo + RAI
Arm/Group Description 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. 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.
Measure Participants 155 78
Number [Percentage of participants]
40.0
25.8%
38.5
49.4%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Selumetinib 75 mg BD + RAI, Placebo + RAI
Comments 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.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.8205
Comments P-value and CIs were calculated using profile likelihood.
Method Regression, Logistic
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.07
Confidence Interval (2-Sided) 95%
0.61 to 1.87
Parameter Dispersion Type:
Value:
Estimation Comments
4. Secondary Outcome
Title Clinical Remission Rate (Expressed as Percentage of Patients in Clinical Remission) at 18 Months Post-RAI Treatment; Subgroup Analysis BRAF/NRAS Mutation Positive
Description 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.
Time Frame At 18 months post-RAI treatment

Outcome Measure Data

Analysis Population Description
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.
Arm/Group Title Selumetinib 75 mg BD + RAI Placebo + RAI
Arm/Group Description 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. 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.
Measure Participants 91 51
Number [Percentage of participants]
37.4
24.1%
41.2
52.8%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Selumetinib 75 mg BD + RAI, Placebo + RAI
Comments 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.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.6549
Comments P-value and CIs were calculated using profile likelihood.
Method Regression, Logistic
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.85
Confidence Interval (2-Sided) 95%
0.42 to 1.73
Parameter Dispersion Type:
Value:
Estimation Comments

Adverse Events

Time Frame Includes adverse events (AEs) with an onset date on or after the date of first dose and up to and including 30 days following the date of last dose of selumetinib/placebo. Overall timeframe for collection of AEs was up to 66 days from the first dose.
Adverse Event Reporting Description 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.
Arm/Group Title Selumetinib 75 mg BD + RAI Placebo + RAI
Arm/Group Description 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. 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.
All Cause Mortality
Selumetinib 75 mg BD + RAI Placebo + RAI
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 1/155 (0.6%) 2/78 (2.6%)
Serious Adverse Events
Selumetinib 75 mg BD + RAI Placebo + RAI
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 7/154 (4.5%) 0/77 (0%)
Gastrointestinal disorders
Gastric haemorrhage 1/154 (0.6%) 1 0/77 (0%) 0
Immune system disorders
Drug hypersensitivity 1/154 (0.6%) 1 0/77 (0%) 0
Infections and infestations
Cellulitis 1/154 (0.6%) 1 0/77 (0%) 0
Metabolism and nutrition disorders
Hypercalcaemia 1/154 (0.6%) 1 0/77 (0%) 0
Nervous system disorders
Syncope 1/154 (0.6%) 1 0/77 (0%) 0
Skin and subcutaneous tissue disorders
Dermatitis acneiform 2/154 (1.3%) 2 0/77 (0%) 0
Other (Not Including Serious) Adverse Events
Selumetinib 75 mg BD + RAI Placebo + RAI
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 141/154 (91.6%) 43/77 (55.8%)
Eye disorders
Periorbital oedema 8/154 (5.2%) 8 0/77 (0%) 0
Vision blurred 16/154 (10.4%) 16 5/77 (6.5%) 5
Gastrointestinal disorders
Constipation 15/154 (9.7%) 15 3/77 (3.9%) 3
Diarrhoea 68/154 (44.2%) 78 12/77 (15.6%) 13
Dry mouth 15/154 (9.7%) 15 3/77 (3.9%) 3
Dyspepsia 8/154 (5.2%) 8 1/77 (1.3%) 1
Nausea 44/154 (28.6%) 44 8/77 (10.4%) 10
Stomatitis 17/154 (11%) 18 4/77 (5.2%) 4
Vomiting 14/154 (9.1%) 14 0/77 (0%) 0
General disorders
Face oedema 9/154 (5.8%) 9 0/77 (0%) 0
Fatigue 44/154 (28.6%) 44 13/77 (16.9%) 13
Oedema peripheral 30/154 (19.5%) 32 4/77 (5.2%) 4
Investigations
Blood creatine phosphokinase increased 31/154 (20.1%) 31 1/77 (1.3%) 1
Weight decreased 0/154 (0%) 0 4/77 (5.2%) 4
Musculoskeletal and connective tissue disorders
Muscle spasms 1/154 (0.6%) 1 4/77 (5.2%) 4
Nervous system disorders
Dysgeusia 6/154 (3.9%) 6 4/77 (5.2%) 4
Headache 8/154 (5.2%) 8 10/77 (13%) 11
Paraesthesia 4/154 (2.6%) 4 4/77 (5.2%) 4
Respiratory, thoracic and mediastinal disorders
Cough 3/154 (1.9%) 3 4/77 (5.2%) 4
Skin and subcutaneous tissue disorders
Rash follicular 13/154 (8.4%) 13 0/77 (0%) 0
Rash macular 12/154 (7.8%) 12 2/77 (2.6%) 2
Acne 13/154 (8.4%) 13 2/77 (2.6%) 2
Dermatitis acneiform 67/154 (43.5%) 70 4/77 (5.2%) 4
Dry skin 12/154 (7.8%) 12 4/77 (5.2%) 4
Pruritus 21/154 (13.6%) 21 3/77 (3.9%) 3
Rash maculo-papular 19/154 (12.3%) 19 4/77 (5.2%) 4
Vascular disorders
Hypertension 20/154 (13%) 23 3/77 (3.9%) 3

Limitations/Caveats

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.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

If the Study is part of a multi-centre clinical trial, the Institution or Investigator agree not to independently publish results of, or make presentations related to, the Study until first occurrence of one of the following: multi-centre primary Publication is published; no multi-centre primary Publication is submitted within 2 years after conclusion, abandonment or termination of the Study at all sites; or Sponsor confirms in writing there will be no multi-centre primary Publication.

Results Point of Contact

Name/Title Global Clinical Lead
Organization AstraZeneca
Phone +1 302 885 1180
Email ClinicalTrialTransparency@astrazeneca.com
Responsible Party:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01843062
Other Study ID Numbers:
  • D1532C00065
  • 2013-000423-14
First Posted:
Apr 30, 2013
Last Update Posted:
Aug 28, 2019
Last Verified:
Aug 1, 2019