Study on Enzalutamide and Flutamide in Patients With Castration Resistant Prostate Cancer
A Randomized Phase IV Study Comparing Enzalutamide Versus Flutamide in Castration-resistant Prostate Cancer (CRPC) Patients Who Have Failed Combined Androgen Blockade Therapy With Bicalutamide Plus Androgen Deprivation Therapy (ADT)
1 other identifier
interventional
206
1 country
47
Brief Summary
The objective of this study was to compare the efficacy and safety of the combination therapy with enzalutamide + androgen deprivation therapy (ADT) and the combination therapy with flutamide + ADT in patients with castration resistant prostate cancer who had relapsed during combined androgen blockade (CAB) therapy with bicalutamide and ADT. This study also investigated the order of alternative antiandrogen therapy (AAT) by changing the 1st line medication after relapse of prostate-specific antigen (PSA).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_4 prostate-cancer
Started Nov 2016
Typical duration for phase_4 prostate-cancer
47 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 27, 2016
CompletedFirst Posted
Study publicly available on registry
September 29, 2016
CompletedStudy Start
First participant enrolled
November 2, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 27, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
March 27, 2020
CompletedResults Posted
Study results publicly available
May 21, 2021
CompletedDecember 9, 2024
November 1, 2024
3.4 years
September 27, 2016
March 25, 2021
November 19, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Time to PSA Progression With 1st Line AAT (TTPP1)
TTPP1 was defined as the period from the date of randomization to the date of PSA progression in the 1st line AAT period. PSA progression was defined according to the consensus guidelines of prostate cancer clinical trials working group 2 (PCWG2). For participants with PSA declines at week 13, the PSA progression date was defined as the date that a ≥ 25% increase and an absolute increase of ≥ 2 ng/mL above the nadir were documented, which was confirmed by a second consecutive value obtained 3 or more weeks later. For participants with no PSA decline at week 13, the PSA progression date was defined as the date that a ≥ 25% increase and an absolute increase of ≥ 2 ng/mL above the baseline were documented. Time to event analysis was performed using kaplan-meier (KM) estimates.
From date of randomization to the date of PSA progression in the 1st line AAT period (Up to 38 months)
Secondary Outcomes (7)
Time to PSA Progression With 2nd Line AAT (TTPP2)
From date of randomization to the date of PSA progression in 2nd line AAT (Up to 38 months)
Percentage of Participants Achieving at Least 50 or 90 Percent (%) Reduction From Baseline and Up To Week 38 in Prostate Specific Antigen (PSA) Response at 1st Line AAT
Baseline and at least 3 weeks after, the lowest PSA decreased by at least 50% or 90% from baseline (Up to 38 months)
Percentage of Participants Achieving at Least 50 or 90 Percent (%) Reduction From Baseline to Week 13 in Prostate Specific Antigen (PSA) Response at 1st Line AAT
Baseline and week 13
Time to PSA Decrease by 50% From Baseline With 1st Line AAT
From date of randomization to the day when the decrease of PSA from baseline by 50% is first identified (Up to 38 months)
Time to Treatment Failure of 1st Line AAT (TTF1)
From date of randomization to discontinuation of 1st line AAT (Up to 38 months)
- +2 more secondary outcomes
Study Arms (2)
Enzalutamide 160 mg 1st line AAT/Flutamide 375 mg 2nd line AAT
EXPERIMENTALParticipants received enzalutamide 160 mg capsules, orally once daily as 1st line of alternative antiandrogen therapy (AAT) until confirmed prostate-specific antigen (PSA) progression, other disease progression, or an intolerable adverse event. After confirmation of PSA progression, other disease progression, or an intolerable adverse event, participants received flutamide 125 mg tablets orally thrice daily after each meal as 2nd line of AAT. Treatment with each drug was continued until the participant met any of the discontinuation criteria or until 2 years from the enrollment of the last participant (approximately 38 months).
Flutamide 375 mg 1st line AAT/Enzaltumide 160 mg 2nd line AAT
EXPERIMENTALParticipants received flutamide 125 mg tablets orally thrice daily after each meal as 1st line of AAT until confirmed PSA progression, other disease progression, or an intolerable adverse event. After confirmed PSA progression, other disease progression, or an intolerable adverse event. participants received enzalutamide 160 mg capsules orally once daily as 2nd line of AAT. Treatment with each drug was continued until the participant met any of the discontinuation criteria or until 2 years from the enrollment of the last participant (approximately 38 months).
Interventions
Oral Capsule
Oral tablet
All subjects must undergo continuous Androgen deprivation therapy with GnRH agonist/antagonist or bilateral orchiectomy during the study period.
Eligibility Criteria
You may qualify if:
- Subject is diagnosed with histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small-cell histology.
- Subject on continuous ADT with Gonadotropin Releasing Hormone (GnRH) agonist/antagonist or bilateral orchiectomy.
- Serum testosterone level below the target level at screening visit.
- Subject with asymptomatic or mildly symptomatic prostate cancer.
- Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Subject has progression of the disease as defined by rising PSA levels or progressive soft tissue or bony disease during CAB therapy in combination of bicalutamide and ADT.
- A sexually active male subject and the subject's female partner who is of childbearing potential must use 2 acceptable birth control methods from screening to 3 months after the last dose of the study drug.
- Subject must agree not to donate sperm from screening to 3 months after the last dose of the study drug.
You may not qualify if:
- Subject with severe concurrent diseases, infections, or complications.
- Subject with confirmed or suspected brain metastasis or active leptomeningeal metastasis.
- Subject with a history of malignant tumor other than prostate cancer in the past 5 years.
- Subject hypersensitive to the ingredients of enzalutamide capsules or flutamide tablets.
- Subject with a history of convulsive attack, or prone to convulsive attack.
- Subject with liver disorder such as viral hepatitis and hepatic cirrhosis, or subject with Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) at screening visit higher than the upper limit of normal.
- Subject received treatment for prostate cancer with cytocidal chemotherapy that includes anti androgenic agents other than bicalutamide, abiraterone, or estramustine.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Astellas Pharma Inclead
- Pfizercollaborator
Study Sites (47)
Site JP00024
Nagoya, Aichi-ken, Japan
Site JP00025
Nagoya, Aichi-ken, Japan
Site JP00038
Matsuyama, Ehime, Japan
Site JP00051
Iizuka, Fukuoka, Japan
Site JP00045
Isesaki, Gunma, Japan
Site JP00005
Maebashi, Gunma, Japan
Site JP00043
ÅŒta, Gunma, Japan
Site JP00054
Hakodate, Hokkaido, Japan
Site JP00001
Sapporo, Hokkaido, Japan
Site JP00002
Sapporo, Hokkaido, Japan
Site JP00048
Sapporo, Hokkaido, Japan
Site JP00055
Mito, Ibaraki, Japan
Site JP00019
Sagamihara, Kanagawa, Japan
Site JP00020
Yokohama, Kanagawa, Japan
Site JP00021
Yokohama, Kanagawa, Japan
Site JP00044
Yokosuka, Kanagawa, Japan
Site JP00046
Kashihara, Nara, Japan
Site JP00033
Kurashiki, Okayama-ken, Japan
Site JP00028
Hirakata, Osaka, Japan
Site JP00030
Sayama, Osaka, Japan
Site JP00027
Suita, Osaka, Japan
Site JP00009
Kitaadachi-gun, Saitama, Japan
Site JP00022
Hamamatsu, Shizuoka, Japan
Site JP00049
Utsunomiya, Tochigi, Japan
Site JP00011
Bunkyo-ku, Tokyo, Japan
Site JP00017
Bunkyo-ku, Tokyo, Japan
Site JP00013
Koto-ku, Tokyo, Japan
Site JP00014
Nakano-ku, Tokyo, Japan
Site JP00016
Shinagawa-ku, Tokyo, Japan
Site JP00018
Shinjuku-ku, Tokyo, Japan
Site JP00034
Ube, Yamaguchi, Japan
Site JP00010
Chiba, Japan
Site JP00053
Chiba, Japan
Site JP00039
Fukuoka, Japan
Site JP00040
Fukuoka, Japan
Site JP00050
Fukuoka, Japan
Site JP00035
Hiroshima, Japan
Site JP00026
Kyoto, Japan
Site JP00006
Nagano, Japan
Site JP00008
Nagano, Japan
Site JP00041
Nagasaki, Japan
Site JP00029
Osaka, Japan
Site JP00031
Osaka, Japan
Site JP00032
Osaka, Japan
Site JP00042
Saga, Japan
Site JP00037
Tokushima, Japan
Site JP00052
Toyama, Japan
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Clinical Trial Disclosure
- Organization
- Astellas Pharma Inc.
Study Officials
- STUDY DIRECTOR
Medical Director
Astellas Pharma Inc
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 27, 2016
First Posted
September 29, 2016
Study Start
November 2, 2016
Primary Completion
March 27, 2020
Study Completion
March 27, 2020
Last Updated
December 9, 2024
Results First Posted
May 21, 2021
Record last verified: 2024-11
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, CSR
- Time Frame
- Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
- Access Criteria
- Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as products terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.