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

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

Tracking Information

• First Submitted Date: March 14, 2013
• First Posted Date: April 30, 2013
• Results First Submitted Date: March 27, 2019
• Results First Posted Date: April 22, 2019
• Last Update Posted Date: August 28, 2019
• Actual Study Start Date: August 27, 2013
• Actual Primary Completion Date: May 18, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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 (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 ]

Current Secondary Outcome Measures (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 (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: Comparing Complete Remission After Treatment With Selumetinib/Placebo in Patient With Differentiated Thyroid Cancer
• 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
• 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: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Differentiated Thyroid Cancer

Intervention

• 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

• 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

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: August 2, 2017): 233
• Original Estimated Enrollment (submitted: April 29, 2013): 228
• Actual Study Completion Date: March 6, 2019
• Actual Primary Completion Date: May 18, 2018 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 130 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Brazil, Denmark, France, Germany, Italy, Poland, Sweden, United States

Administrative Information

• NCT Number: NCT01843062
• Other Study ID Numbers: D1532C00065; 2013-000423-14 ( EudraCT Number )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: AstraZeneca
• Study Sponsor: AstraZeneca
• Collaborators: Not Provided

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

• PRS Account: AstraZeneca
• Verification Date: August 2019