A Phase 2 interventional study of Enzalutamide in Prostate Cancer, DNA and Androgen Receptor Abnormal, sponsored by The Netherlands Cancer Institute. Completed. Open to male participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2017-09-29.
Sponsored by The Netherlands Cancer Institute · Phase 2, Interventional, and Treatment
Rationale: Understanding the mechanisms of enzalutamide as an androgen receptor inhibitor in early prostate cancer could lead to improved patient selection for treatment.
Objective: To study the effects of enzalutamide on surgical margin status and AR / DNA interaction and gene expression.
Intervention : Men with localized prostate cancer will undergo an additional set of targeted tumor biopsies and will be subsequently treated with 3 months of enzalutamide. The prostatectomy specimen will be additionally sampled, ex vivo.
Rationale: Understanding the mechanisms of enzalutamide as an androgen receptor inhibitor in early prostate cancer could lead to improved patient selection for treatment.
Objective: To study the effects of enzalutamide on surgical margin status and AR / DNA interaction and gene expression.
Study design: A phase II prospective single-arm analysis. With a power of 80% to detect an expected reduction in positive surgical margin rate from 34% to 17% the investigators will have to included 55 men. For the AR/DNA interaction patients will serve as there own control since biopsies will be taken before and after enzalutamide treatment.
Study population: Patients over 18 years of age with localized prostate cancer that are planned for prostatectomy.
Intervention : Men with localized prostate cancer will undergo an additional set of targeted tumor biopsies and will be subsequently treated with 3 months of enzalutamide. The prostatectomy specimen will be additionally sampled, ex vivo.
Main study parameters/endpoints: 1. The effects of neoadjuvant androgen ablation on tumor downstaging. 2. The genetic and transcriptional changes caused by neoadjuvant androgen ablation by enzalutamide.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Burden and risks: Patients will be submitted to an additional set of 4 tumor targeted biopsies under local anesthesia and antibiotic prophylaxis. This comprises a 5 minute intervention with an elevated (2%) risk of postbiopsy urinary tract infection. Additionally oral enzalutamide treatment for a period of 3 months will result in temporary signs of androgen ablation such as: hot flushes (20%), headache (12%), diarrhea (1%), and seizures (0.9%). Benefits: neoadjuvant enzalutamide treatment has been shown to result in tumor and prostate downsizing. Earlier neoadjuvant androgen ablation studies with other agents have shown a reduced positive surgical margin rate and reduced intraoperative blood loss
Exclusion Criteria:
This is a single-arm study. Patients will have biopsies, after which they will receive enzalutamide for 3 months. After 3 months they will have a prostatectomy.
Drug: Enzalutamide
Men with localized prostate cancer will undergo an additional set of targeted tumor biopsies and will be subsequently treated with 3 months of enzalutamide. The prostatectomy specimen will be additionally sampled, ex vivo.
Also known as: Xtandi
Effects of enzalutamide on tumor downstaging
To study the effects of enzalutamide on surgical margin status and AR / DNA interaction and gene expression.
Time frame: From baseline (prior to treatment), until disease progression or as long as treatment is tolerated or until study completion (60 months).
Genetic and transcriptional changes caused by enzalutamide
The genetic and transcriptional changes caused by neoadjuvant androgen ablation by enzalutamide.
Time frame: From baseline (prior to treatment), until disease progression or as long as treatment is tolerated or until study completion (60 months).
Clinical down-staging of enzalutamide pretreatment
To assess the effects of 3 months enzalutamide pretreatment on clinical down-staging
Time frame: From baseline (prior to treatment), until disease progression or as long as treatment is tolerated or until study completion (60 months).
AR-chromatin binding alterations and Ki-67 expression
Study the correlation between AR-chromatin binding alterations and Ki-67 expression.
Time frame: From baseline (prior to treatment), until disease progression or as long as treatment is tolerated or until study completion (60 months).
AR-dependant genes such as PSA, human kallikrein and PSMA
Compare the AR-chromatin binding with expression alterations of known AR-dependent genes such as PSA, human kallikrein and PSMA.
Time frame: From baseline (prior to treatment), until disease progression or as long as treatment is tolerated or until study completion (60 months).
Gleason grading
Compare AR-chromatin binding patterns with Gleason grading.
Time frame: From baseline (prior to treatment), until disease progression or as long as treatment is tolerated or until study completion (60 months).
Find associated genes in prostate tissue, using tissue microarray (TMA).
Find associated genes on TMA derived from prostatectomy specimens.
Time frame: From baseline (prior to treatment), until disease progression or as long as treatment is tolerated or until study completion (60 months).
No study locations are listed for this record.
This study is completed, as verified in Aug 2017. You cannot join it, but the record below documents what was studied.
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The Netherlands Cancer Institute