Study on Enzalutamide and Flutamide in Patients With Castration Resistant Prostate Cancer

Prostate Cancer Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02918968
• Other study ID #: 9785-MA-3051
• Status: Completed
• Phase: Phase 4
• Start date: November 2, 2016
• Est. completion date: March 27, 2020

Study information

• Verified date: May 2021
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 206
• Est. completion date: March 27, 2020
• Est. primary completion date: March 27, 2020
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 20 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• Enzalutamide
Oral Capsule
• Flutamide
Oral tablet

Other:
• Androgen deprivation therapy
All subjects must undergo continuous Androgen deprivation therapy with GnRH agonist/antagonist or bilateral orchiectomy during the study period.

Locations

Country	Name	City	State
Japan	Site JP00011	Bunkyo-ku	Tokyo
Japan	Site JP00017	Bunkyo-ku	Tokyo
Japan	Site JP00010	Chiba
Japan	Site JP00053	Chiba
Japan	Site JP00039	Fukuoka
Japan	Site JP00040	Fukuoka
Japan	Site JP00050	Fukuoka
Japan	Site JP00054	Hakodate	Hokkaido
Japan	Site JP00022	Hamamatsu	Shizuoka
Japan	Site JP00028	Hirakata	Osaka
Japan	Site JP00035	Hiroshima
Japan	Site JP00051	Iizuka	Fukuoka
Japan	Site JP00045	Isesaki	Gunma
Japan	Site JP00046	Kashihara	Nara
Japan	Site JP00009	Kitaadachi-gun	Saitama
Japan	Site JP00013	Koto-ku	Tokyo
Japan	Site JP00033	Kurashiki	Okayama
Japan	Site JP00026	Kyoto
Japan	Site JP00005	Maebashi	Gunma
Japan	Site JP00038	Matsuyama	Ehime
Japan	Site JP00055	Mito	Ibaraki
Japan	Site JP00006	Nagano
Japan	Site JP00008	Nagano
Japan	Site JP00041	Nagasaki
Japan	Site JP00024	Nagoya	Aichi
Japan	Site JP00025	Nagoya	Aichi
Japan	Site JP00014	Nakano-ku	Tokyo
Japan	Site JP00029	Osaka
Japan	Site JP00031	Osaka
Japan	Site JP00032	Osaka
Japan	Site JP00030	Osakasayama	Osaka
Japan	Site JP00043	Ota	Gunma
Japan	Site JP00042	Saga
Japan	Site JP00019	Sagamihara	Kanagawa
Japan	Site JP00001	Sapporo	Hokkaido
Japan	Site JP00002	Sapporo	Hokkaido
Japan	Site JP00048	Sapporo	Hokkaido
Japan	Site JP00016	Shinagawa-ku	Tokyo
Japan	Site JP00018	Shinjuku-ku	Tokyo
Japan	Site JP00027	Suita	Osaka
Japan	Site JP00037	Tokushima
Japan	Site JP00052	Toyama
Japan	Site JP00034	Ube	Yamaguchi
Japan	Site JP00049	Utsunomiya	Tochigi
Japan	Site JP00020	Yokohama	Kanagawa
Japan	Site JP00021	Yokohama	Kanagawa
Japan	Site JP00044	Yokosuka	Kanagawa

Sponsors (2)

Lead Sponsor	Collaborator
Astellas Pharma Inc	Pfizer

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Time to PSA Progression With 2nd Line AAT (TTPP2)	TTPP2 was defined as the period from day 1 of the 2nd line AAT to the date of PSA progression with the 2nd line AAT. PSA progression was defined according to the consensus guidelines of 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 estimates.	From date of randomization to the date of PSA progression in 2nd line AAT (Up to 38 months)
Secondary	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	PSA response was defined as PSA decreased by at least 50% or 90% from baseline when at least 3 weeks passed after the lowest PSA decreased by at least 50% or 90% from baseline in the 1st line AAT period after baseline.; Data was reported per each disease stage (M0/N0, M0/N1, M1). 1) M0/N0: No distant metastasis and no lymph node metastasis. 2) M0/N1: Without distant metastasis, but with metastasis in lymph nodes distal to the aortic bifurcation. 3) M1: With distant metastasis (including metastasis in lymph nodes proximal to the aortic bifurcation).	Baseline and at least 3 weeks after, the lowest PSA decreased by at least 50% or 90% from baseline (Up to 38 months)
Secondary	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	PSA response was defined as the lowest PSA at week 13 decreased by at least 50% or 90% from baseline in the 1st line AAT period.; Data was reported per each disease stage (M0/N0, M0/N1, M1). 1) M0/N0: No distant metastasis and no lymph node metastasis. 2) M0/N1: Without distant metastasis, but with metastasis in lymph nodes distal to the aortic bifurcation. 3) M1: With distant metastasis (including metastasis in lymph nodes proximal to the aortic bifurcation).	Baseline and week 13
Secondary	Time to PSA Decrease by 50% From Baseline With 1st Line AAT	Time to PSA decrease by 50% with 1st line AAT was defined as the period from the date of randomization to the day when the decrease of PSA from baseline by 50% is first identified. Time to event analysis was performed using kaplan-meier estimates.; Data was reported per each disease stage (M0/N0, M0/N1, M1). 1) M0/N0: No distant metastasis and no lymph node metastasis. 2) M0/N1: Without distant metastasis, but with metastasis in lymph nodes distal to the aortic bifurcation. 3) M1: With distant metastasis (including metastasis in lymph nodes proximal to the aortic bifurcation).	From date of randomization to the day when the decrease of PSA from baseline by 50% is first identified (Up to 38 months)
Secondary	Time to Treatment Failure of 1st Line AAT (TTF1)	TTF1 was defined as the period from randomization to study drug discontinuation of 1st line AAT for any reason that includes disease progression, onset of adverse events (AEs), participants request, or death. Time to event analysis was performed using kaplan-meier estimates.; Data was reported per each disease stage (M0/N0, M0/N1, M1). 1) M0/N0: No distant metastasis and no lymph node metastasis. 2) M0/N1: Without distant metastasis, but with metastasis in lymph nodes distal to the aortic bifurcation. 3) M1: With distant metastasis (including metastasis in lymph nodes proximal to the aortic bifurcation).	From date of randomization to discontinuation of 1st line AAT (Up to 38 months)
Secondary	Time to Treatment Failure of 2nd Line AAT (TTF2)	TTF2 was defined as the period from randomization to study drug discontinuation of 2nd line AAT for any reason that includes disease progression, onset of AEs, participants request, or death. Time to event analysis was performed using kaplan-meier estimates.	From date of randomization to discontinuation of 2nd line AAT (Up to 38 months)
Secondary	Radiographic Progression-free Survival (rPFS)	rPFS was defined as the period from randomization to the time when radiographic disease progression is observed or death of any cause during the study period, whichever occurs earlier. Time to event analysis was performed using kaplan-meier estimates.; Data was reported per each disease stage (M0/N0, M0/N1, M1). 1) M0/N0: No distant metastasis and no lymph node metastasis. 2) M0/N1: Without distant metastasis, but with metastasis in lymph nodes distal to the aortic bifurcation. 3) M1: With distant metastasis (including metastasis in lymph nodes proximal to the aortic bifurcation).	From date of randomization to the time when radiographic disease progression is observed or death of any cause (up to 38 months)

External Links

•   Link to results on the Astellas Clinical Study Results website.