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試験進捗状況 試験終了/Completed
UMIN試験ID UMIN000016301
受付番号 R000018916
科学的試験名 ビカルタミドを用いたCAB療法後の去勢抵抗性前立腺癌に対する抗アンドロゲン剤交替療法と早期エンザルタミド導入療法の多施設前向き無作為化比較試験
一般公開日(本登録希望日) 2015/01/23
最終更新日 2020/04/06

※ 本ページ収載の情報は、臨床試験に関する情報公開を目的として、UMINが開設しているUMIN臨床試験登録システムに提供された臨床試験情報です。
※ 特定の医薬品や治療法等については、医療関係者や一般の方に向けて広告することは目的としていません。


基本情報/Basic information
一般向け試験名/Public title ビカルタミドを用いたCAB療法後の去勢抵抗性前立腺癌に対する抗アンドロゲン剤交替療法と早期エンザルタミド導入療法の多施設前向き無作為化比較試験 Multicenter, prospective, randomised and comparative study of alternative anti-androgen (AA) therapy and early initiating enzalutamide for castration-resistant prostate cancer (CRPC) after combined androgen blockade (CAB) therapy with bicalutamide.
一般向け試験名略称/Acronym ビカルタミドを用いたCAB療法後の去勢抵抗性前立腺癌に対する抗アンドロゲン剤交替療法と早期エンザルタミド導入療法の多施設前向き無作為化比較試験 Multicenter, prospective, randomised and comparative study of alternative anti-androgen (AA) therapy and early initiating enzalutamide for castration-resistant prostate cancer (CRPC) after combined androgen blockade (CAB) therapy with bicalutamide.
科学的試験名/Scientific Title ビカルタミドを用いたCAB療法後の去勢抵抗性前立腺癌に対する抗アンドロゲン剤交替療法と早期エンザルタミド導入療法の多施設前向き無作為化比較試験 Multicenter, prospective, randomised and comparative study of alternative anti-androgen (AA) therapy and early initiating enzalutamide for castration-resistant prostate cancer (CRPC) after combined androgen blockade (CAB) therapy with bicalutamide.
科学的試験名略称/Scientific Title:Acronym ビカルタミドを用いたCAB療法後の去勢抵抗性前立腺癌に対する抗アンドロゲン剤交替療法と早期エンザルタミド導入療法の多施設前向き無作為化比較試験 Multicenter, prospective, randomised and comparative study of alternative anti-androgen (AA) therapy and early initiating enzalutamide for castration-resistant prostate cancer (CRPC) after combined androgen blockade (CAB) therapy with bicalutamide.
試験実施地域/Region
日本/Japan

対象疾患/Condition
対象疾患名/Condition 去勢抵抗性前立腺癌 Castration-resistant prostate cancer
疾患区分1/Classification by specialty
泌尿器科学/Urology
疾患区分2/Classification by malignancy 悪性腫瘍/Malignancy
ゲノム情報の取扱い/Genomic information いいえ/NO

目的/Objectives
目的1/Narrative objectives1 ビカルタミドを用いたCAB(Bic-CAB)療法後の去勢抵抗性前立腺癌(CRPC)に対して、抗アンドロゲン剤(AA)交替療法とエンザルタミドを用いた2次ホルモン療法の有効性と安全性を比較・評価し、Bic-CAB療法後のCRPCに対する有効な治療方法を検討する。 To compare the efficacy and safety of second line hormonal therapy that using alternative antiandrogen therapy or enzalutamide after bicalutamide-CAB therapy in patients with CRPC.
目的2/Basic objectives2 安全性・有効性/Safety,Efficacy
目的2 -その他詳細/Basic objectives -Others

試験の性質1/Trial characteristics_1
試験の性質2/Trial characteristics_2
試験のフェーズ/Developmental phase

評価/Assessment
主要アウトカム評価項目/Primary outcomes 3ヵ月後のPSA50%低下の割合 Percentage of patients whose prostate specific antigen (PSA) decreased 50 % or more 3 month after initiation
副次アウトカム評価項目/Key secondary outcomes 1) 6ヵ月後のPSA50%低下の割合
2) 3ヵ月後の病勢進行の割合
3) 6ヵ月後の病勢進行の割合
4) PSA-PFS
5) QOL推移(FACT-P)
1) Percentage of patients whose PSA decreased 50 % or more 6 month after initiation
2) Percentage of patients who showed disease progression 3 months after initiation
3) Percentage of patients who showed disease progression 6 months after initiation
4) PSA progression-free survival (PFS)
5) QOL measured by functional assessment of cancer therapy-prostate (FACT-P)

基本事項/Base
試験の種類/Study type 介入/Interventional

試験デザイン/Study design
基本デザイン/Basic design 並行群間比較/Parallel
ランダム化/Randomization ランダム化/Randomized
ランダム化の単位/Randomization unit 個別/Individual
ブラインド化/Blinding オープン/Open -no one is blinded
コントロール/Control 実薬・標準治療対照/Active
層別化/Stratification
動的割付/Dynamic allocation
試験実施施設の考慮/Institution consideration
ブロック化/Blocking
割付コードを知る方法/Concealment

介入/Intervention
群数/No. of arms 2
介入の目的/Purpose of intervention 治療・ケア/Treatment
介入の種類/Type of intervention
医薬品/Medicine
介入1/Interventions/Control_1 エンザルタミドとして160mgを1日1回、経口投与する。 Oral administration of 160 mg enzalutamide once a day
介入2/Interventions/Control_2 フルタミドとして1回125mgを1日3回、食後に経口投与する。 Oral administration of 125 mg flutamide 3 times a day after each meal
介入3/Interventions/Control_3

介入4/Interventions/Control_4

介入5/Interventions/Control_5

介入6/Interventions/Control_6

介入7/Interventions/Control_7

介入8/Interventions/Control_8

介入9/Interventions/Control_9

介入10/Interventions/Control_10


適格性/Eligibility
年齢(下限)/Age-lower limit
20 歳/years-old 以上/<=
年齢(上限)/Age-upper limit

適用なし/Not applicable
性別/Gender 男/Male
選択基準/Key inclusion criteria 1) テストステロン値が50 ng/dL未満の患者
2) 画像上の病勢進行又はPSA再燃を認めた患者(1週間以上の間隔で測定した3回のPSA値がいずれも上昇し、かつ最終測定値が2 ng/ml以上。
ただし、3回目の測定値が2回目の測定値を超えない場合は、さらに4回目の測定を行い、この4回目の測定値が2回目の測定値を超えていること。)
3) ビカルタミドCAB後の再燃患者
4) ECOG PS 0-1 の患者
5) 年齢が20歳以上の患者
6) 文書による同意が取得された患者
1) Less than 50 ng/dL of testosterone
2) Patients who was detected of disease progression on image or relapse of PSA (All PSA values measured 3 times at least one week interval are consecutively increased and final value is 2 ng/mL or more. If third value is not higher than second one, fourth mesurement will be undertaken and its value must be higher than second one.)
3) Patients who relapsed after CAB with bicalutamide
4) ECOG performance status is 0 or 1
5) More than 20 years old
6) Provided written informed consent
除外基準/Key exclusion criteria 1) エンザルタミド、フルタミド、アビラテロン、化学療法のいずれかの治療歴がある患者(ネオアジュバントは除く)
2) 活動性の重複癌が認められる患者
3) 6週間以内にビカルタミドによる治療を受けた患者
4) 前立腺癌に対する全身性の生物学的療法(骨を標的とする既承認薬又はLHRHアナログによる治療を除く)又はその他の抗腫瘍効果を有する薬剤による治療を受けた患者
5) 重篤な合併症を有する患者
6) イクスタンジの成分に対する過敏症の既往歴がある患者
7) フルタミドを含有する製剤に対する過敏症の既往歴がある患者
8) 肝障害がある患者
9) 主治医が不適格と判断した患者
1) Any prior treatment with enzalutamide, flutamide, abiraterone or chemotherapy except for neoadjuvant therapy
2) With active double cancer
3) Any prior treatment with bicalutamide within 6 weeks
4) Patients who received systemic biological therapy for prostate cancer (except for existing approved drug for bone or treatment with LHRH analogue), or received treatment with other antitumor agent for prostate cancer
5) With serious complication
6) Has history of hypersensitivity to enzalutamide or any excipient of enzalutamide
7) Has history of hypersensitivity to flutamide-containing agent
8) With liver dysfunction
9) With considered as inadequate by the investigator
目標参加者数/Target sample size 100

責任研究者/Research contact person
責任研究者/Name of lead principal investigator
達也
ミドルネーム
仲谷
Nakatani
ミドルネーム
Tatsuya
所属組織/Organization 大阪市立大学大学院医学研究科 Osaka City University
所属部署/Division name 泌尿器病態学 Department of Urology
郵便番号/Zip code 545-8585
住所/Address 大阪市阿倍野区旭町1-4-3 1-4-3 Asahimachi, Abeno-ku, Osaka, Japan
電話/TEL 06-6645-3857
Email/Email nakatani@med.osaka-cu.ac.jp

試験問い合わせ窓口/Public contact
試験問い合わせ窓口担当者/Name of contact person
太郎
ミドルネーム
井口
Taro
ミドルネーム
Iguchi
組織名/Organization 大阪市立大学大学院医学研究科 Osaka City University
部署名/Division name 泌尿器病態学 Department of Urology
郵便番号/Zip code 545-8585
住所/Address 大阪市阿倍野区旭町1-4-3 1-4-3 Asahimachi, Abeno-ku, Osaka, Japan
電話/TEL 06-6645-3857
試験のホームページURL/Homepage URL
Email/Email taro@msic.med.osaka-cu.ac.jp

実施責任組織/Sponsor
機関名/Institute 大阪市立大学 Department of Urology, Osaka City University
機関名/Institute
(機関選択不可の場合)
大阪市立大学大学院医学研究科 泌尿器病態学
部署名/Department

研究費提供組織/Funding Source
機関名/Organization アステラス製薬株式会社 Astellas Pharma Inc.
機関名/Organization
(機関選択不可の場合)
アステラス製薬株式会社
組織名/Division
組織の区分/Category of Funding Organization 営利企業/Profit organization
研究費拠出国/Nationality of Funding Organization


その他の関連組織/Other related organizations
共同実施組織/Co-sponsor

その他の研究費提供組織/Name of secondary funder(s)


IRB等連絡先(公開)/IRB Contact (For public release)
組織名/Organization 大阪市立大学医学系研究等倫理審査委員会 Ethical Committee of Osaka City University Graduate School of Medicine
住所/Address 大阪市阿倍野区旭町1-2-7 あべのメディックス6階 Medics building 6F, 1-2-7 Asahimachi, Abeno-ku, Osaka, Japan
電話/Tel 06-6645-3456
Email/Email ethics@med.osaka-cu.ac.jp

他機関から発行された試験ID/Secondary IDs
他機関から発行された試験ID/Secondary IDs はい/YES
試験ID1/Study ID_1 NCT02346578
ID発行機関1/Org. issuing International ID_1 アメリカ国立衛生研究所 National Institutes of Health
試験ID2/Study ID_2
ID発行機関2/Org. issuing International ID_2

治験届/IND to MHLW

試験実施施設/Institutions
試験実施施設名称/Institutions

その他の管理情報/Other administrative information
一般公開日(本登録希望日)/Date of disclosure of the study information
2015 01 23

関連情報/Related information
プロトコル掲載URL/URL releasing protocol https://bmccancer.biomedcentral.com/articles/10.1186/s12885-019-5526-3
試験結果の公開状況/Publication of results 最終結果が公表されている/Published

結果/Result
結果掲載URL/URL related to results and publications https://link.springer.com/article/10.1007/s10147-019-01554-3
組み入れ参加者数/Number of participants that the trial has enrolled 103
主な結果/Results 3ヶ月後のPSA値50%低下の割合はEnz群80.8%(42例),Flu群37.3%(19例)であった(p<0.001).6ヶ月後のPSA値50%低下率,3ヶ月および6ヶ月後の病勢進行率でも同様にEnz群で有意に治療効果が高かった.PSA無増悪生存期間はEnz群:中央値に達せず,Flu群:6.3ヶ月であった(HR: 0.30, 95%CI: 0.16-0.53).【結論】Bic-CAB後のCRPCに対して,EnzはFluよりも高い治療効果を認めた. The 3- (80.8% vs. 35.3%; p <0.001) and 6-month (73.1% vs. 31.4%; p <0.001) prostate-specific antigen response rates were higher in the enzalutamide than in the flutamide group. The 3-month disease progression rates were 6.4% and 38.8% in the enzalutamide and flutamide groups, respectively [HR: 0.16; 95% CI: 0.05-0.47; p <0.001]; the 6-month rates were 11.4% and 51.1%, respectively (HR 0.22; 95% CI 0.09-0.50; p <0.001).
主な結果入力日/Results date posted
2020 04 06
結果掲載遅延/Results Delayed
結果遅延理由/Results Delay Reason

最初の試験結果の出版日/Date of the first journal publication of results
参加者背景/Baseline Characteristics Study population
The study population consists of 100 patients with CRPC who were previously treated with CAB with bicalutamide and whose serum testosterone level is less than 50 ng/dL (1.73 nmol/L) and have progressive disease after confirmation of AWS. Disease progression is defined as at least one of the following criteria: PSA progression, soft-tissue disease progression, or bone disease progression according to the Prostate Cancer Working Group 2 criteria [17].
Eligibility criteria
The inclusion criteria are as follows:
1. Serum testosterone of less than 50 ng/dL
2. Disease progression diagnosed on imaging or PSA progression (i.e., consecutive increase of all PSA values measured at least thrice at a 1-week interval and a final value of 2 ng/mL or more. If the third value is not higher than the second one, a fourth measurement will be taken and its value must be higher than the second one in order for the patient to qualify)
3. Disease progression after CAB with bicalutamide
4. Eastern Cooperative Oncology Group performance status (PS) of 0 or 1
5. Age 20 years or older
6. Written informed consent
The exclusion criteria are as follows:
1. Any prior treatment with enzalutamide, flutamide, abiraterone, or chemotherapy, except for neoadjuvant therapy
2. Presence of active double cancer
3. Any prior treatment with bicalutamide within 6 weeks
4. Systemic biological therapy (except for existing approved drug as bone-modifying agents or treatment with LHRH analogues) or treatment with other antitumor agents for prostate cancer
5. Presence of severe complications
6. History of hypersensitivity to enzalutamide or any other excipient of enzalutamide
7. History of hypersensitivity to flutamide-containing agent
8. Liver dysfunction
9. Participants who are considered as ineligible by the investigator
Study population
The study population consists of 100 patients with CRPC who were previously treated with CAB with bicalutamide and whose serum testosterone level is less than 50 ng/dL (1.73 nmol/L) and have progressive disease after confirmation of AWS. Disease progression is defined as at least one of the following criteria: PSA progression, soft-tissue disease progression, or bone disease progression according to the Prostate Cancer Working Group 2 criteria [17].
Eligibility criteria
The inclusion criteria are as follows:
1. Serum testosterone of less than 50 ng/dL
2. Disease progression diagnosed on imaging or PSA progression (i.e., consecutive increase of all PSA values measured at least thrice at a 1-week interval and a final value of 2 ng/mL or more. If the third value is not higher than the second one, a fourth measurement will be taken and its value must be higher than the second one in order for the patient to qualify)
3. Disease progression after CAB with bicalutamide
4. Eastern Cooperative Oncology Group performance status (PS) of 0 or 1
5. Age 20 years or older
6. Written informed consent
The exclusion criteria are as follows:
1. Any prior treatment with enzalutamide, flutamide, abiraterone, or chemotherapy, except for neoadjuvant therapy
2. Presence of active double cancer
3. Any prior treatment with bicalutamide within 6 weeks
4. Systemic biological therapy (except for existing approved drug as bone-modifying agents or treatment with LHRH analogues) or treatment with other antitumor agents for prostate cancer
5. Presence of severe complications
6. History of hypersensitivity to enzalutamide or any other excipient of enzalutamide
7. History of hypersensitivity to flutamide-containing agent
8. Liver dysfunction
9. Participants who are considered as ineligible by the investigator
参加者の流れ/Participant flow Methods of recruitment and random allocation
Patient recruitment started in January 2015 and is targeted to end by March 2018. Eligible patients are randomly assigned to one of the two treatment groups through the data center at DOT International Inc (which was responsible for data entry, coding, security, and storage, including any related processes to promote data quality). Patients will be randomly allocated to the enzalutamide or flutamide group via dynamic allocation using metastatic condition (M0, M1) and baseline PSA level as prognostic factors.
Methods of recruitment and random allocation
Patient recruitment started in January 2015 and is targeted to end by March 2018. Eligible patients are randomly assigned to one of the two treatment groups through the data center at DOT International Inc (which was responsible for data entry, coding, security, and storage, including any related processes to promote data quality). Patients will be randomly allocated to the enzalutamide or flutamide group via dynamic allocation using metastatic condition (M0, M1) and baseline PSA level as prognostic factors.
有害事象/Adverse events Safety
The treatment-related AEs are summarized in Table 3. In total, 29 and 6 patients in the enzalutamide group and flutamide group, respectively, developed treatment-related AEs. Furthermore, AE-related treatment discontinuation was observed in 8 (decreased appetite: 4; anaphylactic reaction, seizure, QT prolongation, and rash: 1 each) and 6 patients (hepatic dysfunction and diarrhea: 2 each; breast pain and anorexia: 1 each) in the enzalutamide and flutamide groups, respectively. Meanwhile, AE-related dose reduction was required 21 and 4 patients in the enzalutamide and flutamide groups, respectively. As shown in Table 3, fatigue, decreased appetite, nausea, anemia, and dysgeusia were observed in at least 2% of patients in the enzalutamide group; the corresponding AEs in the flutamide group included hepatic dysfunction, decreased appetite, anemia, and diarrhea. Grade >=3 AEs occurred in 7 and 4 patients in the enzalutamide and flutamide groups, respectively; 1 patient in the enzalutamide group experienced a seizure, which was not severe and disappeared with discontinuation of the drug.
Safety
The treatment-related AEs are summarized in Table 3. In total, 29 and 6 patients in the enzalutamide group and flutamide group, respectively, developed treatment-related AEs. Furthermore, AE-related treatment discontinuation was observed in 8 (decreased appetite: 4; anaphylactic reaction, seizure, QT prolongation, and rash: 1 each) and 6 patients (hepatic dysfunction and diarrhea: 2 each; breast pain and anorexia: 1 each) in the enzalutamide and flutamide groups, respectively. Meanwhile, AE-related dose reduction was required 21 and 4 patients in the enzalutamide and flutamide groups, respectively. As shown in Table 3, fatigue, decreased appetite, nausea, anemia, and dysgeusia were observed in at least 2% of patients in the enzalutamide group; the corresponding AEs in the flutamide group included hepatic dysfunction, decreased appetite, anemia, and diarrhea. Grade >=3 AEs occurred in 7 and 4 patients in the enzalutamide and flutamide groups, respectively; 1 patient in the enzalutamide group experienced a seizure, which was not severe and disappeared with discontinuation of the drug.
評価項目/Outcome measures Endpoints of the study
The primary endpoint of the study is a PSA response rate (i.e., the ratio of patients whose PSA decreased by >=50% from baseline) at 3 months. Meanwhile, the secondary endpoints in the OCUU-CRPC study are as follows:
1. PSA progression rate at 3 months
2. PSA response rate at 6 months: If initial enzalutamide therapy is switched to other treatments due to disease progression before 6 months, such cases are regarded as “non-responders” regardless of the efficacy of the subsequent treatment. In addition, the PSA response rate in patients in whom flutamide is switched to enzalutamide will be calculated to determine the efficacy of enzalutamide in the flutamide to enzalutamide cohort.
3. PSA progression rate at 6 months
4. Change in quality of life (QOL) as assessed using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) scale in Japanese
5. PSA progression-free survival that is calculated for the initial drug in each arm
6. Adverse events (AEs)
Endpoints of the study
The primary endpoint of the study is a PSA response rate (i.e., the ratio of patients whose PSA decreased by >=50% from baseline) at 3 months. Meanwhile, the secondary endpoints in the OCUU-CRPC study are as follows:
1. PSA progression rate at 3 months
2. PSA response rate at 6 months: If initial enzalutamide therapy is switched to other treatments due to disease progression before 6 months, such cases are regarded as 'non-responders' regardless of the efficacy of the subsequent treatment. In addition, the PSA response rate in patients in whom flutamide is switched to enzalutamide will be calculated to determine the efficacy of enzalutamide in the flutamide to enzalutamide cohort.
3. PSA progression rate at 6 months
4. Change in quality of life (QOL) as assessed using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) scale in Japanese
5. PSA progression-free survival that is calculated for the initial drug in each arm
6. Adverse events (AEs)
個別症例データ共有計画/Plan to share IPD

個別症例データ共有計画の詳細/IPD sharing Plan description


試験進捗状況/Progress
試験進捗状況/Recruitment status 試験終了/Completed
プロトコル確定日/Date of protocol fixation
2014 12 25
倫理委員会による承認日/Date of IRB
2014 08 20
登録・組入れ開始(予定)日/Anticipated trial start date
2015 01 26
フォロー終了(予定)日/Last follow-up date
2018 09 30
入力終了(予定)日/Date of closure to data entry
2018 10 30
データ固定(予定)日/Date trial data considered complete
2018 11 15
解析終了(予定)日/Date analysis concluded
2019 02 01

その他/Other
その他関連情報/Other related information


管理情報/Management information
登録日時/Registered date
2015 01 22
最終更新日/Last modified on
2020 04 06


閲覧ページへのリンク/Link to view the page
URL(日本語) https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000018916
URL(英語) https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000018916

研究計画書
登録日時 ファイル名
2020/04/06 最終版 臨床研究計画書(第五稿)10.26.pdf

研究症例データ仕様書
登録日時 ファイル名
2020/04/06 解析計画書1.1版19.1.28.pdf

研究症例データ
登録日時 ファイル名
2020/04/06 190201_解析結果.zip


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