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

Primary Purpose

Differentiated Thyroid Cancer

Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Selumetinib
Placebo
Radioactive Iodine Therapy
Sponsored by
AstraZeneca
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Differentiated Thyroid Cancer focused on measuring Selumetinib, Differentiated Thyroid Cancer , AZD6244

Eligibility Criteria

18 Years - 130 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

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Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Selumetinib

Placebo

Arm Description

Selumetinib plus Radioactive Iodine Therapy

Placebo plus Radioactive Iodine Therapy

Outcomes

Primary Outcome Measures

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.

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
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
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
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.

Full Information

First Posted
March 14, 2013
Last Updated
August 27, 2019
Sponsor
AstraZeneca
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1. Study Identification

Unique Protocol Identification Number
NCT01843062
Brief Title
Comparing Complete Remission After Treatment With Selumetinib/Placebo in Patient With Differentiated Thyroid Cancer
Acronym
ASTRA
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2019
Overall Recruitment Status
Terminated
Why 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.
Study Start Date
August 27, 2013 (Actual)
Primary Completion Date
May 18, 2018 (Actual)
Study Completion Date
March 6, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca

4. Oversight

Data Monitoring Committee
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Differentiated Thyroid Cancer
Keywords
Selumetinib, Differentiated Thyroid Cancer , AZD6244

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
233 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Selumetinib
Arm Type
Experimental
Arm Description
Selumetinib plus Radioactive Iodine Therapy
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo plus Radioactive Iodine Therapy
Intervention Type
Drug
Intervention Name(s)
Selumetinib
Intervention Description
3 capsules of 25 mg strength orally twice a day for approximately 5 weeks treatment period
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
3 capsules ( to match Selumetinib capsules) orally twice a day for approximately 5 weeks treatment period
Intervention Type
Drug
Intervention Name(s)
Radioactive Iodine Therapy
Intervention Description
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)
Primary Outcome Measure Information:
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
Secondary Outcome Measure Information:
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
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
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
130 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alan Ho, M.D., PHD
Organizational Affiliation
Memorial Sloan Kettering Cancer Centre, 1275 York Avenue, New York, NY 10065.
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Tracy C Cunningham, M.D
Organizational Affiliation
Melbourn Science Park, Cambridge Road, Melbourn, Hertfordshire, SG8 6HB, UK
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
Research Site
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72205
Country
United States
Facility Name
Research Site
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
Research Site
City
Torrance
State/Province
California
ZIP/Postal Code
90502
Country
United States
Facility Name
Research Site
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Research Site
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Facility Name
Research Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Research Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Research Site
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Research Site
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Research Site
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Research Site
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45219
Country
United States
Facility Name
Research Site
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Research Site
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19014
Country
United States
Facility Name
Research Site
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232-8148
Country
United States
Facility Name
Research Site
City
Barretos
ZIP/Postal Code
14784-400
Country
Brazil
Facility Name
Research Site
City
Porto Alegre
Country
Brazil
Facility Name
Research Site
City
Ribeirão Preto
Country
Brazil
Facility Name
Research Site
City
Rio de Janeiro
Country
Brazil
Facility Name
Research Site
City
São José do Rio Preto
Country
Brazil
Facility Name
Research Site
City
São Paulo
Country
Brazil
Facility Name
Research Site
City
Odense C
ZIP/Postal Code
5000
Country
Denmark
Facility Name
Research Site
City
Angers Cedex 01
ZIP/Postal Code
49033
Country
France
Facility Name
Research Site
City
Bordeaux Cedex
ZIP/Postal Code
33076
Country
France
Facility Name
Research Site
City
Caen Cedex 5
ZIP/Postal Code
41076
Country
France
Facility Name
Research Site
City
Lyon
Country
France
Facility Name
Research Site
City
Toulouse Cedex 9
ZIP/Postal Code
31059
Country
France
Facility Name
Research Site
City
Villejuif Cedex
ZIP/Postal Code
94805
Country
France
Facility Name
Research Site
City
Augsburg
ZIP/Postal Code
86156
Country
Germany
Facility Name
Research Site
City
Essen
ZIP/Postal Code
45122
Country
Germany
Facility Name
Research Site
City
Leipzig
ZIP/Postal Code
04103
Country
Germany
Facility Name
Research Site
City
Catania
ZIP/Postal Code
95122
Country
Italy
Facility Name
Research Site
City
Napoli
ZIP/Postal Code
80131
Country
Italy
Facility Name
Research Site
City
Pisa
ZIP/Postal Code
56124
Country
Italy
Facility Name
Research Site
City
Roma
ZIP/Postal Code
00161
Country
Italy
Facility Name
Research Site
City
Gliwice
ZIP/Postal Code
44-101
Country
Poland
Facility Name
Research Site
City
Kielce
ZIP/Postal Code
25-734
Country
Poland
Facility Name
Research Site
City
Poznań
ZIP/Postal Code
60-355
Country
Poland
Facility Name
Research Site
City
Warszawa
ZIP/Postal Code
02-507
Country
Poland
Facility Name
Research Site
City
Warszawa
ZIP/Postal Code
02-781
Country
Poland
Facility Name
Research Site
City
Zgierz
ZIP/Postal Code
95-100
Country
Poland
Facility Name
Research Site
City
Göteborg
ZIP/Postal Code
413 45
Country
Sweden
Facility Name
Research Site
City
Linköping
ZIP/Postal Code
581 85
Country
Sweden
Facility Name
Research Site
City
Lund
ZIP/Postal Code
221 85
Country
Sweden
Facility Name
Research Site
City
Stockholm
ZIP/Postal Code
171 76
Country
Sweden

12. IPD Sharing Statement

Citations:
PubMed Identifier
35192411
Citation
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.
Results Reference
derived
Links:
URL
http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&studyid=1176&filename=Final-D1532C00065-Statistical%20Analysis%20Plan-edition%204_Redaction-checked.pdf
Description
Statistical Analysis Plan-edition 4_Redacted
URL
http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&studyid=1176&filename=Final-d1532c00065-redacted%20CSP-checked.pdf
Description
Redacted CSP
URL
https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&amp;parentIdentifier=D1532C00065&amp;attachmentIdentifier=49f06c23-25bc-4cde-bd5c-904895d052e2&amp;fileName=Final-D1532C00065-Statistical_Analysis_Plan-edition_4_Redaction-checked-v1.0000.pdf&amp;versionIdentifier=
Description
Related Info

Learn more about this trial

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

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