UMIN-CTR 臨床試験登録情報の閲覧

一般向け試験名/Public title

日本語
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

英語
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

日本語
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

英語
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

日本語
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

英語
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

日本語
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

英語
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

対象疾患名/Condition

日本語
去勢抵抗性前立腺癌

英語
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1/Narrative objectives1

日本語
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。

英語
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

日本語

英語

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

主要アウトカム評価項目/Primary outcomes

日本語
3ヵ月後のPSA50％低下の割合

英語
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

日本語
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）

英語
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)

試験の種類/Study type

介入/Interventional

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

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

日本語
エンザルタミドとして160mgを1日1回、経口投与する。

英語
Oral administration of 160 mg enzalutamide once a day

介入2/Interventions/Control_2

日本語
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。

英語
Oral administration of 125 mg flutamide 3 times a day after each meal

介入3/Interventions/Control_3

日本語

英語

介入4/Interventions/Control_4

日本語

英語

介入5/Interventions/Control_5

日本語

英語

介入6/Interventions/Control_6

日本語

英語

介入7/Interventions/Control_7

日本語

英語

介入8/Interventions/Control_8

日本語

英語

介入9/Interventions/Control_9

日本語

英語

介入10/Interventions/Control_10

日本語

英語

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

日本語
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

英語
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

日本語
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

英語
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/Name of lead principal investigator

日本語

名	達也
ミドルネーム
姓	仲谷

英語

名	Nakatani
ミドルネーム
姓	Tatsuya

所属組織/Organization

日本語
大阪市立大学大学院医学研究科

英語
Osaka City University

所属部署/Division name

日本語
泌尿器病態学

英語
Department of Urology

郵便番号/Zip code

545-8585

住所/Address

日本語
大阪市阿倍野区旭町1-4-3

英語
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担当者/Name of contact person

日本語

名	太郎
ミドルネーム
姓	井口

英語

名	Taro
ミドルネーム
姓	Iguchi

組織名/Organization

日本語
大阪市立大学大学院医学研究科

英語
Osaka City University

部署名/Division name

日本語
泌尿器病態学

英語
Department of Urology

郵便番号/Zip code

545-8585

住所/Address

日本語
大阪市阿倍野区旭町1-4-3

英語
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

機関名/Institute

日本語
大阪市立大学

英語
Department of Urology, Osaka City University

機関名/Institute
（機関選択不可の場合）

日本語
大阪市立大学大学院医学研究科 泌尿器病態学

部署名/Department

日本語

個人名/Personal name

日本語

英語

機関名/Organization

日本語
アステラス製薬株式会社

英語
Astellas Pharma Inc.

機関名/Organization
（機関選択不可の場合）

日本語
アステラス製薬株式会社

組織名/Division

日本語

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

日本語

英語

共同実施組織/Co-sponsor

日本語

英語

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

日本語

英語

組織名/Organization

日本語
大阪市立大学医学系研究等倫理審査委員会

英語
Ethical Committee of Osaka City University Graduate School of Medicine

住所/Address

日本語
大阪市阿倍野区旭町1-2-7　あべのメディックス6階

英語
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

はい/YES

試験ID1/Study ID_1

NCT02346578

ID発行機関1/Org. issuing International ID_1

日本語
アメリカ国立衛生研究所

英語
National Institutes of Health

試験ID2/Study ID_2

ID発行機関2/Org. issuing International ID_2

日本語

英語

治験届/IND to MHLW

試験実施施設名称/Institutions

一般公開日（本登録希望日）/Date of disclosure of the study information

2015

年

01

月

23

日

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

日本語
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．

英語
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

年

04

月

06

日

結果掲載遅延/Results Delayed

結果遅延理由/Results Delay Reason

日本語

英語

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

日本語
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

英語
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

日本語
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.

英語
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

日本語
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.

英語
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

日本語
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)

英語
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

日本語

英語

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

日本語

英語

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

年

12

月

25

日

倫理委員会による承認日/Date of IRB

2014

年

08

月

20

日

登録・組入れ開始（予定）日/Anticipated trial start date

2015

年

01

月

26

日

フォロー終了(予定)日/Last follow-up date

2018

年

09

月

30

日

入力終了(予定)日/Date of closure to data entry

2018

年

10

月

30

日

データ固定（予定）日/Date trial data considered complete

2018

年

11

月

15

日

解析終了(予定)日/Date analysis concluded

2019

年

02

月

01

日

その他関連情報/Other related information

日本語

英語

登録日時/Registered date

2015

年

01

月

22

日

最終更新日/Last modified on

2020

年

04

月

06

日

閲覧ページへのリンク/Link to view the page

日本語
https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000018916

英語
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000018916