Nexavar® Versus Placebo in Locally Advanced/Metastatic RAI-Refractory Differentiated Thyroid Cancer
2018年8月15日 更新者：Bayer
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
Trial of sorafenib versus placebo in the treatment of locally advanced or metastatic differentiated thyroid cancer refractory to radioiodine
調査の概要
詳細な説明
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(either double only or double blind and open label) for reasons other than death, lost to follow-up or consent withdrawn entered long-term follow up
研究の種類
介入
入学 (実際)
417
段階
- フェーズ 3
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究場所
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California
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Los Angeles、California、アメリカ、90048
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Stanford、California、アメリカ、94305-5820
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Connecticut
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New Haven、Connecticut、アメリカ、06520
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Georgia
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Atlanta、Georgia、アメリカ、30322
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Massachusetts
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Boston、Massachusetts、アメリカ、02118
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Michigan
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Ann Arbor、Michigan、アメリカ、48109
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Missouri
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Saint Louis、Missouri、アメリカ、63110
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New Mexico
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Albuquerque、New Mexico、アメリカ、87106
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New York
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New York、New York、アメリカ、10029
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Pennsylvania
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Philadelphia、Pennsylvania、アメリカ、19104
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Pittsburgh、Pennsylvania、アメリカ、15213-1863
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Texas
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Houston、Texas、アメリカ、77030
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Washington
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Seattle、Washington、アメリカ、98109-1023
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Cardiff、イギリス、CF14 2TL
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Glasgow、イギリス、G12 0YN
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Leeds、イギリス、LS9 7TF
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London、イギリス、SE1 9RT
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London、イギリス、SM2 5PT
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Manchester、イギリス、M20 4BX
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Newcastle Upon Tyne、イギリス、NE7 7DN
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Sutton、イギリス、SM2 5PT
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Aberdeenshire
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Aberdeen、Aberdeenshire、イギリス、AB25 2ZN
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Campania
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Napoli、Campania、イタリア、80131
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Liguria
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Genova、Liguria、イタリア、16132
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Lombardia
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Milano、Lombardia、イタリア、20133
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Milano、Lombardia、イタリア、20122
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Milano、Lombardia、イタリア、20162
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Sicilia
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Catania、Sicilia、イタリア、95029
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Toscana
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Pisa、Toscana、イタリア、56124
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Siena、Toscana、イタリア、53100
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Umbria
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Perugia、Umbria、イタリア、06126
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Groningen、オランダ、9713 GZ
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Leiden、オランダ、2333 ZA
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Wien、オーストリア、1090
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Riyadh、サウジアラビア、11211
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Göteborg、スウェーデン、413 45
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Linköping、スウェーデン、581 85
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Lund、スウェーデン、221 85
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Stockholm、スウェーデン、171 76
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Barcelona、スペイン、08035
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Madrid
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Majadahonda、Madrid、スペイン、28222
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Odense C、デンマーク、5000
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Bayern
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Erlangen、Bayern、ドイツ、91054
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München、Bayern、ドイツ、81377
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Würzburg、Bayern、ドイツ、97080
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Nordrhein-Westfalen
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Essen、Nordrhein-Westfalen、ドイツ、45122
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Köln、Nordrhein-Westfalen、ドイツ、50924
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Sachsen
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Leipzig、Sachsen、ドイツ、04103
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Angers、フランス、49933
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Bordeaux、フランス、33076
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Caen、フランス、14076
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LILLE cedex、フランス、59037
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Lyon、フランス、69373
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MARSEILLE cedex、フランス、13273
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Paris、フランス、75651
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Villejuif、フランス、94805
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Sofia、ブルガリア、1527
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Bruxelles - Brussel、ベルギー、1000
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Gliwice、ポーランド、44-101
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Poznan、ポーランド、60-355
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Warszawa、ポーランド、02-781
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Warszawa、ポーランド、04-141
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Obninsk、ロシア連邦、249036
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Beijing、中国、100730
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Beijing、中国、100021
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Chengdu、中国、610041
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Hangzhou、中国、310022
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Shanghai、中国、200127
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Shanghai、中国、200030
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Tianjin、中国、300060
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Guangdong
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Guangzhou、Guangdong、中国、510060
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Daejeon、大韓民国、301-721
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Seoul、大韓民国、137-701
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Seoul、大韓民国、110-744
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Seoul、大韓民国、120-752
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Seoul、大韓民国、135-710
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Seoul Teugbyeolsi
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Seoul、Seoul Teugbyeolsi、大韓民国、138-736
- Asan Medical Center
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Aichi
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Nagoya、Aichi、日本、466-8560
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Nagoya、Aichi、日本、464-8681
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Chiba
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Kashiwa、Chiba、日本、277-8577
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Tokyo
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Koto-ku、Tokyo、日本、135-8550
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参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
18年歳以上 (大人、高齢者)
健康ボランティアの受け入れ
いいえ
受講資格のある性別
全て
説明
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
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：4倍
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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実験的：Sorafenib (Nexavar, BAY43-9006)
Participants received 2 tablets of Sorafenib (2×200 mg) orally twice daily (12 hours apart without food), 28 days comprise a cycle
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Sorafenib 400 mg will be administered orally, twice daily (approximately every 12 hours).
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プラセボコンパレーター：Placebo
Participants received 2 tablets of Sorafenib-matching placebo orally twice daily (12 hours apart without food), 28 days comprise a cycle
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Placebo (2 tablets) will be administered orally, twice daily (approximately every 12 hours).
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Progression-free Survival (PFS) Based on Central Assessment Incl. Clinical Progression Due to Bone Irradiation
時間枠：Final analysis to be performed when approximately 267 progression-free survival events (centrally assessed) had occurred, study duration approximately three years
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PFS=time from randomization to first observed disease progression (radiological according to central assessment or clinical due to bone irradiation, whichever is earlier), or death due to any cause, if death occurred before progression.
Progression was assessed by RECIST criteria, version 1.0, modified for bone lesions.
PFS for participants without disease progression or death at the time of analysis or unblinding were censored at the last date of tumor assessment before unblinding.
Participants with no tumor evaluation after baseline were censored at Day 1. PD (Progression Disease)=At least a 20% increase in sum of longest diameters (LD) of measured lesions taking as reference the smallest sum LD on study since the treatment started or the appearance of 1 or more new lesions.
New lesions also constituted PD.
In exceptional circumstances, unequivocal progression of a nonmeasured lesion may have been accepted as evidence of disease progression in participants with measurable disease.
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Final analysis to be performed when approximately 267 progression-free survival events (centrally assessed) had occurred, study duration approximately three years
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Overall Survival (OS)
時間枠：From randomization of the first subject until the database cut-off (30 AUG 2017), study duration approximately eight years
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Overall survival was defined as the time (days) from date of randomization to date of death due to any cause.
Subjects still alive at the time of analysis were censored at their date of last contact.
Since the median value could not be estimated due to censored data, the percentage of participants who died is presented.
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From randomization of the first subject until the database cut-off (30 AUG 2017), study duration approximately eight years
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Time to Progression (TTP) Based on Central Assessment Incl. Clinical Progression Due to Bone Irradiation
時間枠：From randomization of the first subject until the database cut-off (31 Aug 2012), study duration approximately three years
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Time to progression was defined at the time (days) from randomization to progression (based on central assessment [radiological and clinical progression due to bone irradiation])
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From randomization of the first subject until the database cut-off (31 Aug 2012), study duration approximately three years
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Disease Control Rate (DCR) Based on Central Assessment
時間枠：From randomization of the first subject until the database cut-off (31 Aug 2012), study duration approximately three years
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Disease control rate was defined as the proportion of subjects whose best response was complete response (CR), partial response (PR), or stable disease (SD).
Per Response Evaluation Criteria in Solid Tumors (RECIST) criteria, CR and PR were to be confirmed by another scan at least 4 weeks later; SD had to be documented at least 4 weeks after date of randomization.
CR = Disappearance of all clinical and radiological evidence of tumor (both target and no-target).
PR = At least a 30% decrease in the sum of LD of target lesions taking as reference the baseline sum.
SD = steady state of disease which is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
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From randomization of the first subject until the database cut-off (31 Aug 2012), study duration approximately three years
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Response Rate Based on Central Assessment
時間枠：From randomization of the first subject until the database cut-off (31 Aug 2012), study duration approximately three years
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Response rate was defined as the proportion of subjects whose best response was CR or PR.
Per RECIST, CR and PR was to be confirmed by another scan at least 4 weeks later.
CR = Disappearance of all clinical and radiological evidence of tumor (both target and no-target).
PR = At least a 30% decrease in the sum of LD of target lesions taking as reference the baseline sum.
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From randomization of the first subject until the database cut-off (31 Aug 2012), study duration approximately three years
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Duration of Response (DOR) Based on Central Assessment
時間枠：From randomization of the first subject until the database cut-off (31 Aug 2012), study duration approximately three years
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Duration of response was defined as the time from the first documented objective response of PR or CR, whichever was noted earlier, to disease progression or death (if death occurred before progression was documented).
CR = Disappearance of all clinical and radiological evidence of tumor (both target and no-target).
PR = At least a 30% decrease in the sum of LD of target lesions taking as reference the baseline sum.
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From randomization of the first subject until the database cut-off (31 Aug 2012), study duration approximately three years
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Maximum Percent Reduction in Target Lesion Size Based on Central Assessment
時間枠：From randomization of the first subject until the database cut-off (31 Aug 2012), study duration approximately three years
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The magnitude of change from baseline in target lesion size in evaluable participants with scans was determined.
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From randomization of the first subject until the database cut-off (31 Aug 2012), study duration approximately three years
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AUC(0-12h),ss (Area Under the Concentration Time Curve From Time 0 to 12 Hours at Steady State)
時間枠：A single pharmacokinetic plasma sample was collected at steady state (after 14 days of uninterrupted, unmodified sorafenib dosing)
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Sorafenib AUC(0-12h),ss (area under the concentration time curve from time 0 to 12 hours at steady state) was estimated from the steady state plasma concentration.
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A single pharmacokinetic plasma sample was collected at steady state (after 14 days of uninterrupted, unmodified sorafenib dosing)
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協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
出版物と役立つリンク
研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。
一般刊行物
- Worden F, Fassnacht M, Shi Y, Hadjieva T, Bonichon F, Gao M, Fugazzola L, Ando Y, Hasegawa Y, Park DJ, Shong YK, Smit JW, Chung J, Kappeler C, Meinhardt G, Schlumberger M, Brose MS. Safety and tolerability of sorafenib in patients with radioiodine-refractory thyroid cancer. Endocr Relat Cancer. 2015 Dec;22(6):877-87. doi: 10.1530/ERC-15-0252.
- Brose MS, Nutting CM, Jarzab B, Elisei R, Siena S, Bastholt L, de la Fouchardiere C, Pacini F, Paschke R, Shong YK, Sherman SI, Smit JW, Chung J, Kappeler C, Pena C, Molnar I, Schlumberger MJ; DECISION investigators. Sorafenib in radioactive iodine-refractory, locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 3 trial. Lancet. 2014 Jul 26;384(9940):319-28. doi: 10.1016/S0140-6736(14)60421-9. Epub 2014 Apr 24.
- Brose MS, Nutting CM, Sherman SI, Shong YK, Smit JW, Reike G, Chung J, Kalmus J, Kappeler C, Schlumberger M. Rationale and design of decision: a double-blind, randomized, placebo-controlled phase III trial evaluating the efficacy and safety of sorafenib in patients with locally advanced or metastatic radioactive iodine (RAI)-refractory, differentiated thyroid cancer. BMC Cancer. 2011 Aug 11;11:349. doi: 10.1186/1471-2407-11-349.
- Brose MS, Schlumbeger M, Jeffers M, Kappeler C, Meinhardt G, Pena CEA. Analysis of Biomarkers and Association With Clinical Outcomes in Patients With Differentiated Thyroid Cancer: Subanalysis of the Sorafenib Phase III DECISION Trial. Clin Cancer Res. 2019 Dec 15;25(24):7370-7380. doi: 10.1158/1078-0432.CCR-18-3439. Epub 2019 Sep 26.
- Capdevila J, Matos I, Mancuso FM, Iglesias C, Nuciforo P, Zafon C, Palmer HG, Ogbah Z, Muinos L, Hernando J, Villacampa G, Pena CE, Tabernero J, Brose MS, Schlumberger M, Vivancos A. Identification of Expression Profiles Defining Distinct Prognostic Subsets of Radioactive-Iodine Refractory Differentiated Thyroid Cancer from the DECISION Trial. Mol Cancer Ther. 2020 Jan;19(1):312-317. doi: 10.1158/1535-7163.MCT-19-0211. Epub 2019 Sep 20.
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始 (実際)
2009年10月15日
一次修了 (実際)
2012年8月31日
研究の完了 (実際)
2017年8月30日
試験登録日
最初に提出
2009年9月24日
QC基準を満たした最初の提出物
2009年9月24日
最初の投稿 (見積もり)
2009年9月25日
学習記録の更新
投稿された最後の更新 (実際)
2018年9月13日
QC基準を満たした最後の更新が送信されました
2018年8月15日
最終確認日
2018年8月1日
詳しくは
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。