Nexavar® Versus Placebo in Locally Advanced/Metastatic RAI-Refractory Differentiated Thyroid Cancer

A Double-Blind Randomized Phase III Study Evaluating the Efficacy and Safety of Sorafenib Compared to Placebo in Locally Advanced/Metastatic RAI-Refractory Differentiated Thyroid Cancer

Sponsors

Lead Sponsor: Bayer

Collaborator: Amgen

Source Bayer
Brief Summary

Trial of sorafenib versus placebo in the treatment of locally advanced or metastatic differentiated thyroid cancer refractory to radioiodine

Detailed Description

Eligible subjects were randomized 1:1 to sorafenib 800 mg daily or matching placebo. Progression was assessed every 8 weeks by modified RECIST criteria. Subjects had the option to unblind study treatment after progression and to receive open label sorafenib regardless of initial treatment assignment. Following discontinuation of study treatment, subjects were followed for survival every 3 months in long-term follow-up. Subjects who terminated study treatment (either double only or double blind and open label) for reasons other than death, lost to follow-up or consent withdrawn entered long-term follow up

Overall Status Completed
Start Date October 15, 2009
Completion Date August 30, 2017
Primary Completion Date August 31, 2012
Phase Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
Progression-free Survival (PFS) Based on Central Assessment Incl. Clinical Progression Due to Bone Irradiation Final analysis to be performed when approximately 267 progression-free survival events (centrally assessed) had occurred, study duration approximately three years
Secondary Outcome
Measure Time Frame
Overall Survival (OS) From randomization of the first subject until the database cut-off (30 AUG 2017), study duration approximately eight years
Time to Progression (TTP) Based on Central Assessment Incl. Clinical Progression Due to Bone Irradiation From randomization of the first subject until the database cut-off (31 Aug 2012), study duration approximately three years
Disease Control Rate (DCR) Based on Central Assessment From randomization of the first subject until the database cut-off (31 Aug 2012), study duration approximately three years
Response Rate Based on Central Assessment From randomization of the first subject until the database cut-off (31 Aug 2012), study duration approximately three years
Duration of Response (DOR) Based on Central Assessment From randomization of the first subject until the database cut-off (31 Aug 2012), study duration approximately three years
Maximum Percent Reduction in Target Lesion Size Based on Central Assessment From randomization of the first subject until the database cut-off (31 Aug 2012), study duration approximately three years
AUC(0-12h),ss (Area Under the Concentration Time Curve From Time 0 to 12 Hours at Steady State) A single pharmacokinetic plasma sample was collected at steady state (after 14 days of uninterrupted, unmodified sorafenib dosing)
Enrollment 417
Condition
Intervention

Intervention Type: Drug

Intervention Name: Sorafenib (Nexavar, BAY43-9006)

Description: Sorafenib 400 mg will be administered orally, twice daily (approximately every 12 hours).

Arm Group Label: Sorafenib (Nexavar, BAY43-9006)

Intervention Type: Drug

Intervention Name: Placebo

Description: Placebo (2 tablets) will be administered orally, twice daily (approximately every 12 hours).

Arm Group Label: Placebo

Eligibility

Criteria:

Inclusion Criteria:

- Locally advanced or metastatic differentiated thyroid cancer (papillary, follicular and Hurthle cell)

- Poorly differentiated and other thyroid variants (e.g. insular, tall cell, etc.) are eligible provided that the histology has no medullary differentiation nor anaplastic features

- Progression within 14 months (RECIST [Response Evaluation Criteria in Solid Tumors] should be used as a basis for the assessment of disease progression)

- RAI (radioactive iodine) refractory

Exclusion Criteria:

- Histologic subtypes of thyroid cancer other than differentiated (i.e. like anaplastic and medullary carcinoma, lymphoma or sarcoma)

- Prior anti-cancer treatment with tyrosine kinase inhibitors, monoclonal antibodies (licensed or investigational) that target VEGF (vascular endothelial growth factor) or VEGF Receptors or other targeted agents

- Prior anti-cancer treatment for thyroid cancer with use of chemotherapy (low dose chemotherapy for radiosensitization is allowed) or Thalidomide or any of its derivatives

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Bayer Study Director Study Director Bayer
Location
Facility:
| Los Angeles, California, 90048, United States
| Stanford, California, 94305-5820, United States
| New Haven, Connecticut, 06520, United States
| Atlanta, Georgia, 30322, United States
| Boston, Massachusetts, 02118, United States
| Ann Arbor, Michigan, 48109, United States
| Saint Louis, Missouri, 63110, United States
| Albuquerque, New Mexico, 87106, United States
| New York, New York, 10029, United States
| Philadelphia, Pennsylvania, 19104, United States
| Pittsburgh, Pennsylvania, 15213-1863, United States
| Houston, Texas, 77030, United States
| Seattle, Washington, 98109-1023, United States
| Wien, 1090, Austria
| Bruxelles - Brussel, 1000, Belgium
| Sofia, 1527, Bulgaria
| Guangzhou, Guangdong, 510060, China
| Beijing, 100021, China
| Beijing, 100730, China
| Chengdu, 610041, China
| Hangzhou, 310022, China
| Shanghai, 200030, China
| Shanghai, 200127, China
| Tianjin, 300060, China
| Odense C, 5000, Denmark
| Angers, 49933, France
| Bordeaux, 33076, France
| Caen, 14076, France
| LILLE cedex, 59037, France
| Lyon, 69373, France
| MARSEILLE cedex, 13273, France
| Paris, 75651, France
| Villejuif, 94805, France
| Erlangen, Bayern, 91054, Germany
| München, Bayern, 81377, Germany
| Würzburg, Bayern, 97080, Germany
| Essen, Nordrhein-Westfalen, 45122, Germany
| Köln, Nordrhein-Westfalen, 50924, Germany
| Leipzig, Sachsen, 04103, Germany
| Napoli, Campania, 80131, Italy
| Genova, Liguria, 16132, Italy
| Milano, Lombardia, 20122, Italy
| Milano, Lombardia, 20133, Italy
| Milano, Lombardia, 20162, Italy
| Catania, Sicilia, 95029, Italy
| Pisa, Toscana, 56124, Italy
| Siena, Toscana, 53100, Italy
| Perugia, Umbria, 06126, Italy
| Nagoya, Aichi, 464-8681, Japan
| Nagoya, Aichi, 466-8560, Japan
| Kashiwa, Chiba, 277-8577, Japan
| Koto-ku, Tokyo, 135-8550, Japan
Asan Medical Center | Seoul, Seoul Teugbyeolsi, 138-736, Korea, Republic of
| Daejeon, 301-721, Korea, Republic of
| Seoul, 110-744, Korea, Republic of
| Seoul, 120-752, Korea, Republic of
| Seoul, 135-710, Korea, Republic of
| Seoul, 137-701, Korea, Republic of
| Groningen, 9713 GZ, Netherlands
| Leiden, 2333 ZA, Netherlands
| Gliwice, 44-101, Poland
| Poznan, 60-355, Poland
| Warszawa, 02-781, Poland
| Warszawa, 04-141, Poland
| Obninsk, 249036, Russian Federation
| Riyadh, 11211, Saudi Arabia
| Majadahonda, Madrid, 28222, Spain
| Barcelona, 08035, Spain
| Göteborg, 413 45, Sweden
| Linköping, 581 85, Sweden
| Lund, 221 85, Sweden
| Stockholm, 171 76, Sweden
| Aberdeen, Aberdeenshire, AB25 2ZN, United Kingdom
| Cardiff, CF14 2TL, United Kingdom
| Glasgow, G12 0YN, United Kingdom
| Leeds, LS9 7TF, United Kingdom
| London, SE1 9RT, United Kingdom
| London, SM2 5PT, United Kingdom
| Manchester, M20 4BX, United Kingdom
| Newcastle Upon Tyne, NE7 7DN, United Kingdom
| Sutton, SM2 5PT, United Kingdom
Location Countries

Austria

Belgium

Bulgaria

China

Denmark

France

Germany

Italy

Japan

Korea, Republic of

Netherlands

Poland

Russian Federation

Saudi Arabia

Spain

Sweden

United Kingdom

United States

Verification Date

August 2018

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Sorafenib (Nexavar, BAY43-9006)

Type: Experimental

Description: Participants received 2 tablets of Sorafenib (2×200 mg) orally twice daily (12 hours apart without food), 28 days comprise a cycle

Label: Placebo

Type: Placebo Comparator

Description: Participants received 2 tablets of Sorafenib-matching placebo orally twice daily (12 hours apart without food), 28 days comprise a cycle

Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Source: ClinicalTrials.gov