Dynamics of Androgen Receptor Genomics and Transcriptomics After Neoadjuvant Androgen Ablation

Prostate Cancer Clinical Trial

— DARANA  

Official title:

Dynamics of Androgen Receptor Genomics and Transcriptomics After Neoadjuvant Androgen Ablation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03297385
• Other study ID #: N14DAR
• Status: Completed
• Phase: Phase 2
• First received: April 13, 2017
• Last updated: September 28, 2017
• Start date: August 28, 2014
• Est. completion date: April 1, 2017

Study information

• Verified date: August 2017
• Source: The Netherlands Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: April 1, 2017
• Est. primary completion date: April 1, 2017
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Men over 18 years of age.

2. clinically non-metastasized prostate cancer, tumor that can be imaged (TRUS or MRI) in order to allow for accurate preoperative biopsies.

3. Gleason score 7-10

4. written informed consent

5. WHO performance 0-1

Exclusion Criteria:

1. A history of seizures.

2. Clinically nodal metastases.

3. Prostatitis or urinary tract infection.

4. Androgen ablative therapy within 6 weeks of inclusion (including 5 alpha-reductase inhibitors).

5. Tumor of the prostate that can not be visualized by TRUS or MRI.

Related Conditions & MeSH terms

• Androgen Receptor Abnormal
• DNA
• Prostate Cancer
• Prostatic Neoplasms

Intervention

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.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
The Netherlands Cancer Institute	Astellas Pharma Inc

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Effects of enzalutamide on tumor downstaging	To study the effects of enzalutamide on surgical margin status and AR / DNA interaction and gene expression.	From baseline (prior to treatment), until disease progression or as long as treatment is tolerated or until study completion (60 months).
Primary	Genetic and transcriptional changes caused by enzalutamide	The genetic and transcriptional changes caused by neoadjuvant androgen ablation by enzalutamide.	From baseline (prior to treatment), until disease progression or as long as treatment is tolerated or until study completion (60 months).
Secondary	Clinical down-staging of enzalutamide pretreatment	To assess the effects of 3 months enzalutamide pretreatment on clinical down-staging	From baseline (prior to treatment), until disease progression or as long as treatment is tolerated or until study completion (60 months).
Secondary	AR-chromatin binding alterations and Ki-67 expression	Study the correlation between AR-chromatin binding alterations and Ki-67 expression.	From baseline (prior to treatment), until disease progression or as long as treatment is tolerated or until study completion (60 months).
Secondary	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.	From baseline (prior to treatment), until disease progression or as long as treatment is tolerated or until study completion (60 months).
Secondary	Gleason grading	Compare AR-chromatin binding patterns with Gleason grading.	From baseline (prior to treatment), until disease progression or as long as treatment is tolerated or until study completion (60 months).
Secondary	Find associated genes in prostate tissue, using tissue microarray (TMA).	Find associated genes on TMA derived from prostatectomy specimens.	From baseline (prior to treatment), until disease progression or as long as treatment is tolerated or until study completion (60 months).