Clinical trial NCT02918968: Study on Enzalutamide and Flutamide in Patients With Castration Resistant Prostate Cancer
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Prostate Cancer
Keywords: enzalutamide
Xtandi
Prostate Cancer
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
Collaborators: name: Pfizer
First posted: 2016-09-29
Enrollment: 206
Sex: MALE
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Time to PSA Progression With 1st Line AAT (TTPP1)
timeFrame: From date of randomization to the date of PSA progression in the 1st line AAT period (Up to 38 months)
Secondary outcomes:
measure: Time to PSA Progression With 2nd Line AAT (TTPP2)
timeFrame: From date of randomization to the date of PSA progression in 2nd line AAT (Up to 38 months)
measure: 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
timeFrame: Baseline and at least 3 weeks after, the lowest PSA decreased by at least 50% or 90% from baseline (Up to 38 months)
measure: 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
timeFrame: Baseline and week 13
measure: Time to PSA Decrease by 50% From Baseline With 1st Line AAT
timeFrame: From date of randomization to the day when the decrease of PSA from baseline by 50% is first identified (Up to 38 months)
measure: Time to Treatment Failure of 1st Line AAT (TTF1)
timeFrame: From date of randomization to discontinuation of 1st line AAT (Up to 38 months)
measure: Time to Treatment Failure of 2nd Line AAT (TTF2)
timeFrame: From date of randomization to discontinuation of 2nd line AAT (Up to 38 months)
measure: Radiographic Progression-free Survival (rPFS)
timeFrame: From date of randomization to the time when radiographic disease progression is observed or death of any cause (up to 38 months)
Other outcomes:
Locations:
city: Nagoya
country: Japan
facility: Site JP00024
state: Aichi
city: Nagoya
country: Japan
facility: Site JP00025
state: Aichi
city: Matsuyama
country: Japan
facility: Site JP00038
state: Ehime
city: Iizuka
country: Japan
facility: Site JP00051
state: Fukuoka
city: Isesaki
country: Japan
facility: Site JP00045
state: Gunma
city: Maebashi
country: Japan
facility: Site JP00005
state: Gunma
city: Ota
country: Japan
facility: Site JP00043
state: Gunma
city: Hakodate
country: Japan
facility: Site JP00054
state: Hokkaido
city: Sapporo
country: Japan
facility: Site JP00001
state: Hokkaido
city: Sapporo
country: Japan
facility: Site JP00002
state: Hokkaido
city: Sapporo
country: Japan
facility: Site JP00048
state: Hokkaido
city: Mito
country: Japan
facility: Site JP00055
state: Ibaraki
city: Sagamihara
country: Japan
facility: Site JP00019
state: Kanagawa
city: Yokohama
country: Japan
facility: Site JP00020
state: Kanagawa
city: Yokohama
country: Japan
facility: Site JP00021
state: Kanagawa
city: Yokosuka
country: Japan
facility: Site JP00044
state: Kanagawa
city: Kashihara
country: Japan
facility: Site JP00046
state: Nara
city: Kurashiki
country: Japan
facility: Site JP00033
state: Okayama
city: Hirakata
country: Japan
facility: Site JP00028
state: Osaka
city: Osakasayama
country: Japan
facility: Site JP00030
state: Osaka
city: Suita
country: Japan
facility: Site JP00027
state: Osaka
city: Kitaadachi-gun
country: Japan
facility: Site JP00009
state: Saitama
city: Hamamatsu
country: Japan
facility: Site JP00022
state: Shizuoka
city: Utsunomiya
country: Japan
facility: Site JP00049
state: Tochigi
city: Bunkyo-ku
country: Japan
facility: Site JP00011
state: Tokyo
city: Bunkyo-ku
country: Japan
facility: Site JP00017
state: Tokyo
city: Koto-ku
country: Japan
facility: Site JP00013
state: Tokyo
city: Nakano-ku
country: Japan
facility: Site JP00014
state: Tokyo
city: Shinagawa-ku
country: Japan
facility: Site JP00016
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Site JP00018
state: Tokyo
city: Ube
country: Japan
facility: Site JP00034
state: Yamaguchi
city: Chiba
country: Japan
facility: Site JP00010
city: Chiba
country: Japan
facility: Site JP00053
city: Fukuoka
country: Japan
facility: Site JP00039
city: Fukuoka
country: Japan
facility: Site JP00040
city: Fukuoka
country: Japan
facility: Site JP00050
city: Hiroshima
country: Japan
facility: Site JP00035
city: Kyoto
country: Japan
facility: Site JP00026
city: Nagano
country: Japan
facility: Site JP00006
city: Nagano
country: Japan
facility: Site JP00008
city: Nagasaki
country: Japan
facility: Site JP00041
city: Osaka
country: Japan
facility: Site JP00029
city: Osaka
country: Japan
facility: Site JP00031
city: Osaka
country: Japan
facility: Site JP00032
city: Saga
country: Japan
facility: Site JP00042
city: Tokushima
country: Japan
facility: Site JP00037
city: Toyama
country: Japan
facility: Site JP00052
Study officials:
affiliation: Astellas Pharma Inc
name: Medical Director
role: STUDY_DIRECTOR
References: