UMIN-CTR Clinical Trial

Unique ID issued by UMIN	UMIN000016301
Receipt number	R000018916
Scientific Title	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.
Date of disclosure of the study information	2015/01/23
Last modified on	2020/04/06 11:13:51

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Basic information

Public title

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.

Acronym

Scientific Title

Scientific Title:Acronym

Region

Japan

Condition

Castration-resistant prostate cancer

Classification by specialty

Urology

Classification by malignancy

Malignancy

Genomic information

Objectives

Narrative objectives1

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.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Assessment

Primary outcomes

Percentage of patients whose prostate specific antigen (PSA) decreased 50 % or more 3 month after initiation

Key secondary outcomes

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)

Base

Study type

Interventional

Study design

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Open -no one is blinded

Control

Active

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

Intervention

No. of arms

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

Oral administration of 160 mg enzalutamide once a day

Interventions/Control_2

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

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Eligibility

Age-lower limit

20 years-old <=

Age-upper limit

Not applicable

Gender

Male

Key inclusion criteria

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

Key exclusion criteria

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

Target sample size

100

Research contact person

Name of lead principal investigator

1st name Nakatani

Middle name

Last name Tatsuya

Organization

Osaka City University

Division name

Department of Urology

Zip code

545-8585

Address

1-4-3 Asahimachi, Abeno-ku, Osaka, Japan

TEL

06-6645-3857

Email

nakatani@med.osaka-cu.ac.jp

Public contact

Name of contact person

1st name Taro

Middle name

Last name Iguchi

Organization

Osaka City University

Division name

Department of Urology

Zip code

545-8585

Address

1-4-3 Asahimachi, Abeno-ku, Osaka, Japan

TEL

06-6645-3857

Homepage URL

Email

taro@msic.med.osaka-cu.ac.jp

Sponsor or person

Institute

Department of Urology, Osaka City University

Institute

Department

Personal name

Funding Source

Organization

Astellas Pharma Inc.

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

Other related organizations

Co-sponsor

Name of secondary funder(s)

IRB Contact (For public release)

Organization

Ethical Committee of Osaka City University Graduate School of Medicine

Address

Medics building 6F, 1-2-7 Asahimachi, Abeno-ku, Osaka, Japan

Tel

06-6645-3456

Email

ethics@med.osaka-cu.ac.jp

Secondary IDs

YES

Study ID_1

NCT02346578

Org. issuing International ID_1

National Institutes of Health

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Other administrative information

Date of disclosure of the study information

2015 Year 01 Month 23 Day

Related information

URL releasing protocol

https://bmccancer.biomedcentral.com/articles/10.1186/s12885-019-5526-3

Publication of results

Published

Result

URL related to results and publications

https://link.springer.com/article/10.1007/s10147-019-01554-3

Number of participants that the trial has enrolled

103

Results

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).

Results date posted

2020 Year 04 Month 06 Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

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

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.

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.

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)

Plan to share IPD

IPD sharing Plan description

Progress

Recruitment status

Completed

Date of protocol fixation

2014 Year 12 Month 25 Day

Date of IRB

2014 Year 08 Month 20 Day

Anticipated trial start date

2015 Year 01 Month 26 Day

Last follow-up date

2018 Year 09 Month 30 Day

Date of closure to data entry

2018 Year 10 Month 30 Day

Date trial data considered complete

2018 Year 11 Month 15 Day

Date analysis concluded

2019 Year 02 Month 01 Day

Other

Other related information

Management information

Registered date

2015 Year 01 Month 22 Day

Last modified on

2020 Year 04 Month 06 Day

Link to view the page

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

Research Plan
Registered date	File name
2020/04/06	最終版　臨床研究計画書（第五稿）10.26.pdf

Research case data specifications
Registered date	File name
2020/04/06	解析計画書1.1版19.1.28.pdf

Research case data
Registered date	File name
2020/04/06	190201_解析結果.zip

Single case data URL

Value
https://center6.umin.ac.jp/ice/18916