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

Astellas

Status and phase: Completed; Phase 4

Conditions: Prostate Cancer

Treatments: Drug: Enzalutamide; Drug: Flutamide; Other: Androgen deprivation therapy

Study type: Interventional

Funder types: Industry

Identifiers

NCT02918968

9785-MA-3051

Details and patient eligibility

About

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).

Enrollment: 206 patients

Sex: Male

Ages: 20+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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206 participants in 2 patient groups

Enzalutamide 160 mg 1st line AAT/Flutamide 375 mg 2nd line AAT

Experimental group

Description:

Participants 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).

Treatment:

Other: Androgen deprivation therapy

Drug: Flutamide

Drug: Enzalutamide

Flutamide 375 mg 1st line AAT/Enzaltumide 160 mg 2nd line AAT

Experimental group

Description:

Participants 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).

Treatment:

Other: Androgen deprivation therapy

Drug: Flutamide

Drug: Enzalutamide