Differentiated Thyroid CancerPhase 3ASTRANCT01843062
Comparing Complete Remission After Treatment With Selumetinib/Placebo in Patient With Differentiated Thyroid Cancer
A Phase 3 study testing Selumetinib and Radioactive Iodine Therapy in people with Differentiated Thyroid Cancer, run by AstraZeneca at 45 sites in 8 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 130 years
- Conditions the study is for
- Differentiated Thyroid Cancer
- What is being tested?
- Selumetinib and Radioactive Iodine Therapy
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 233 participants
- Where
- 45 sitesin 8 countries
- Study dates
- 27 Aug 2013to 6 Mar 2019
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 130 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
45 sites in 8 countries.
45 sites in 8 countries
United States15 sites
Research Site
Aurora, Colorado, 80045
Research Site
Birmingham, Alabama, 35233
Research Site
Boston, Massachusetts, 02114
Research Site
Boston, Massachusetts, 02215
Research Site
Cincinnati, Ohio, 45219
Research Site
Durham, North Carolina, 27710
Research Site
Little Rock, Arkansas, 72205
Research Site
Los Angeles, California, 90048
Research Site
Nashville, Tennessee, 37232-8148
Research Site
New York, New York, 10029
Research Site
New York, New York, 10065
Research Site
Philadelphia, Pennsylvania, 19014
Research Site
Portland, Oregon, 97239
Research Site
Torrance, California, 90502
Research Site
Washington D.C., District of Columbia, 20010
Brazil6 sites
Research Site
Barretos, 14784-400
Research Site
Porto Alegre
Research Site
Ribeirão Preto
Research Site
Rio de Janeiro
Research Site
São José do Rio Preto
Research Site
São Paulo
France6 sites
Research Site
Angers, 49033
Research Site
Bordeaux, 33076
Research Site
Caen, 41076
Research Site
Lyon
Research Site
Toulouse, 31059
Research Site
Villejuif, 94805
Poland6 sites
Research Site
Gliwice, 44-101
Research Site
Kielce, 25-734
Research Site
Poznan, 60-355
Research Site
Warsaw, 02-507
Research Site
Warsaw, 02-781
Research Site
Zgierz, 95-100
Italy4 sites
Research Site
Catania, 95122
Research Site
Naples, 80131
Research Site
Pisa, 56124
Research Site
Roma, 00161
Sweden4 sites
Research Site
Gothenburg, 413 45
Research Site
Linköping, 581 85
Research Site
Lund, 221 85
Research Site
Stockholm, 171 76
Germany3 sites
Research Site
Augsburg, 86156
Research Site
Essen, 45122
Research Site
Leipzig, 04103
About this study
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
The study is designed to evaluate the clinical efficacy, safety and tolerability of selumetinib with radioactive iodine therapy in patients with differentiated thyroid cancer.
Read the 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.
- Conditions
- Differentiated Thyroid Cancer
- Being tested
- Selumetinib, Placebo, Radioactive Iodine Therapy
- Keywords
- Selumetinib, Differentiated Thyroid Cancer , AZD6244
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SelumetinibDrug
3 capsules of 25 mg strength orally twice a day for approximately 5 weeks treatment period
PlaceboDrug
3 capsules ( to match Selumetinib capsules) orally twice a day for approximately 5 weeks treatment period
Radioactive Iodine TherapyDrug
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)
| Study group | Role | What they receive |
|---|---|---|
| Selumetinib | Experimental | Selumetinib plus Radioactive Iodine Therapy Receives: Drug: Selumetinib; Drug: Radioactive Iodine Therapy |
| Placebo | Placebo comparator | Placebo plus Radioactive Iodine Therapy Receives: Drug: Placebo; Drug: Radioactive Iodine Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: At 18 months post-RAI treatment
Secondary outcomes (3)
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.
Measured: At 18 months post-RAI treatment
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.
Measured: At 18 months post-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
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.
Measured: At 18 months post-RAI treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Apr 2013 (estimated)
- Study start27 Aug 2013
- Primary completion18 May 2018
- Study completion6 Mar 2019
Why it stopped: Study was terminated based on the findings of primary analysis at 18 months post-RAI treatment. Patients pending 3 year follow up had end of study phone call.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Differentiated Thyroid CancerStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 233 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Alan Ho, M.D., PHD, Principal investigator, Memorial Sloan Kettering Cancer Centre, 1275 York Avenue, New York, NY 10065.Tracy C Cunningham, M.D, Study director, Melbourn Science Park, Cambridge Road, Melbourn, Hertfordshire, SG8 6HB, UK
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01843062
- Sponsor's protocol ID
- D1532C00065
- Other IDs
- 2013-000423-14
- Acronym
- ASTRA
- Status last verified
- Aug 2019
- First submitted
- 14 Mar 2013
- Last updated
- 28 Aug 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 35192411
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01843062
- Acronym / sponsor ID
- ASTRA / D1532C00065
- Conditions
- Differentiated Thyroid Cancer
- Keywords
- Selumetinib, Differentiated Thyroid Cancer , AZD6244
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study was terminated based on the findings of primary analysis at 18 months post-RAI treatment. Patients pending 3 year follow up had end of study phone call.
- Enrolment
- 233 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 27 Aug 2013 (actual)
- Primary completion
- 18 May 2018 (actual)
- Study completion
- 6 Mar 2019 (actual)
- First posted
- 30 Apr 2013 (estimated)
- Results
- Posted 22 Apr 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Selumetinib | Experimental | Drug: Selumetinib, Drug: Radioactive Iodine TherapySelumetinib plus Radioactive Iodine Therapy |
| Placebo | Placebo comparator | Drug: Placebo, Drug: Radioactive Iodine TherapyPlacebo plus Radioactive Iodine Therapy |
Who may qualify
- Ages
- 18 to 130 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 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
Key exclusion criteria (1 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Selumetinib3 capsules of 25 mg strength orally twice a day for approximately 5 weeks treatment period | Drug | Selumetinib |
| Placebo3 capsules ( to match Selumetinib capsules) orally twice a day for approximately 5 weeks treatment period | Drug | Placebo |
| Radioactive Iodine TherapyA 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) | Drug | Placebo, Selumetinib |
Primary outcome
Complete Remission Rate (Expressed as Percentage of Patients in Complete Remission) at 18 Months Post-RAI Treatment; ITT Analysis Set
Time frame: 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.
3 secondary outcomes
Complete Remission Rate (Expressed as Percentage of Patients in Complete Remission) at 18 Months Post-RAI Treatment; Subgroup Analysis BRAF/NRAS Mutation Positive
Time frame: At 18 months post-RAI treatment
Clinical Remission Rate (Expressed as Percentage of Patients in Clinical Remission) at 18 Months Post-RAI Treatment; ITT Analysis Set
Time frame: At 18 months post-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
Time frame: At 18 months post-RAI treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Aug 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35192411Ho 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.
- Statistical Analysis Plan-edition 4\_RedactedLink provided by the sponsor.
- Redacted CSPLink provided by the sponsor.
- Related InfoLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alan Ho, M.D., PHD principal investigator
Memorial Sloan Kettering Cancer Centre, 1275 York Avenue, New York, NY 10065.
Tracy C Cunningham, M.D study director
Melbourn Science Park, Cambridge Road, Melbourn, Hertfordshire, SG8 6HB, UK
45 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Selumetinib and Radioactive Iodine Therapy in people with Differentiated Thyroid Cancer, run by AstraZeneca at 45 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 28 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 45 sites in United States, Brazil, France, Poland, Italy and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Apr 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complete Remission Rate (Expressed as Percentage of Patients in Complete Remission) at 18 Months Post-RAI Treatment; ITT Analysis Set (time frame: At 18 months post-RAI treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01843062, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Aug 2019.