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

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ClinicalTrials.gov Identifier: NCT01843062
Recruitment Status : Terminated (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.)
First Posted : April 30, 2013
Results First Posted : April 22, 2019
Last Update Posted : August 28, 2019
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE March 14, 2013
First Posted Date  ICMJE April 30, 2013
Results First Submitted Date  ICMJE March 27, 2019
Results First Posted Date  ICMJE April 22, 2019
Last Update Posted Date August 28, 2019
Actual Study Start Date  ICMJE August 27, 2013
Actual Primary Completion Date May 18, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 27, 2019)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: April 29, 2013)
  • Complete remission rate in overall study population [ Time Frame: Measured at 18 months post radioactive iodine treatment ]
  • Complete remission rate in sub-group of patients with tumours known to be mutation positive for v-raf murine sarcoma viral oncogene homolog B1 or NRAS [ Time Frame: Measured at 18 months post radioactive iodine treatment ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 27, 2019)
  • 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 ]
    Patients were defined to be in complete remission if all of the following criteria were demonstrated:
    1. Serum Tg levels <1 ng/mL during rhTSH stimulation, in the absence of interfering Tg antibodies, as assessed by standardised central laboratory analysis.
    2. No confirmed evidence of thyroid cancer on neck ultrasound, as assessed by investigator site review.
    3. No confirmed radiological evidence of thyroid cancer, as assessed by blinded independent central review.
    4. No histopathological evidence of thyroid cancer FNA/biopsy when performed, as assessed by investigator site review.
    5. No further thyroid cancer therapy was administered in the first 18 months following the initial RAI treatment.
  • 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 ]
    Patients were defined to be in clinical remission if all of the following criteria were demonstrated:
    1. Serum Tg levels <1 ng/mL during rhTSH stimulation, in the absence of interfering Tg antibodies, as assessed by standardised central laboratory analysis.
    2. No confirmed evidence of thyroid cancer on neck ultrasound, as assessed by investigator site review.
    3. No evidence of thyroid cancer on diagnostic whole body scan (WBS), as assessed by blinded independent central review.
    4. No histopathological evidence of thyroid cancer on FNA/biopsy when performed to clarify equivocal ultrasound findings, as assessed by investigator site review.
    5. No further thyroid cancer therapy was administered in the first 18 months following the initial RAI treatment.
  • 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 ]
    Patients were defined to be in clinical remission if all of the following criteria were demonstrated:
    1. Serum Tg levels <1 ng/mL during rhTSH stimulation, in the absence of interfering Tg antibodies, as assessed by standardised central laboratory analysis.
    2. No confirmed evidence of thyroid cancer on neck ultrasound, as assessed by investigator site review.
    3. No evidence of thyroid cancer on diagnostic WBS, as assessed by blinded independent central review.
    4. No histopathological evidence of thyroid cancer on FNA/biopsy when performed to clarify equivocal ultrasound findings, as assessed by investigator site review.
    5. No further thyroid cancer therapy was administered in the first 18 months following the initial RAI treatment.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 29, 2013)
  • Clinical remission rate in overall study population [ Time Frame: Measured at 18 months post radioactive iodine treatment ]
  • Clinical remission rate in sub-group of patients with tumours known to be mutation positive for v-raf murine sarcoma viral oncogene homolog B1 or NRAS [ Time Frame: Measured at 18 months post radioactive iodine treatment ]
  • Frequency of adverse events graded according to the National Cancer Institute Common Terminology Criteria for AEs (CTCAE)" [ Time Frame: Measured throughout the study until 3 years post radioactive iodine treatment ]
  • Selumetinib concentration profile over time [ Time Frame: In total 8 blood samples will be collected: 4 samples on pre defined time windows on Day1, and 4 samples on Day 29 or Day 30 ]
  • N-desmethyl selumetinib concentration profile over time [ Time Frame: in total 8 blood samples will be collected: 4 samples on pre defined time windows on Day1, and 4 samples on Day 29 or Day 30 ]
  • Selumetinib amide concentration profile over time [ Time Frame: in total 8 blood samples will be collected: 4 samples on pre defined time windows on Day1, and 4 samples on Day 29 or Day 30 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Comparing Complete Remission After Treatment With Selumetinib/Placebo in Patient With Differentiated Thyroid Cancer
Official Title  ICMJE 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
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.
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Differentiated Thyroid Cancer
Intervention  ICMJE
  • Drug: Selumetinib
    3 capsules of 25 mg strength orally twice a day for approximately 5 weeks treatment period
  • 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)
Study Arms  ICMJE
  • Experimental: Selumetinib
    Selumetinib plus Radioactive Iodine Therapy
    Interventions:
    • Drug: Selumetinib
    • Drug: Radioactive Iodine Therapy
  • Placebo Comparator: Placebo
    Placebo plus Radioactive Iodine Therapy
    Interventions:
    • Drug: Placebo
    • Drug: Radioactive Iodine Therapy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: August 2, 2017)
233
Original Estimated Enrollment  ICMJE
 (submitted: April 29, 2013)
228
Actual Study Completion Date  ICMJE March 6, 2019
Actual Primary Completion Date May 18, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 130 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Brazil,   Denmark,   France,   Germany,   Italy,   Poland,   Sweden,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01843062
Other Study ID Numbers  ICMJE D1532C00065
2013-000423-14 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party AstraZeneca
Study Sponsor  ICMJE AstraZeneca
Collaborators  ICMJE Not Provided
Investigators  ICMJE
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
PRS Account AstraZeneca
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP