ASTRA: Comparing Complete Remission After Treatment With Selumetinib/Placebo in Patient With Differentiated Thyroid Cancer
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
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
- 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
- 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.
- 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.
- 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
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.- D1532C00065
- 2013-000423-14
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
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 |
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 |
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 |
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
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 |
ClinicalTrialTransparency@astrazeneca.com |
- D1532C00065
- 2013-000423-14