Dynamics of Androgen Receptor Genomics and Transcriptomics After Neoadjuvant Androgen Ablation

NCT ID: NCT03297385

Last Updated: 2017-09-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-08-28

Study Completion Date

2017-04-01

Brief Summary

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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.

Detailed Description

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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

Conditions

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Prostate Cancer DNA Androgen Receptor Abnormal

Keywords

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Prostate Cancer Androgen Receptor Genomics Enzalutamide Prostatectomy Neoadjuvant androgen ablation

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

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% we 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.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Prostatectomy after enzalutamide

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.

Group Type EXPERIMENTAL

Enzalutamide

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type DRUG

Other Intervention Names

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Xtandi

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Astellas Pharma Inc

INDUSTRY

Sponsor Role collaborator

The Netherlands Cancer Institute

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

References

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Zhang M, Moreno-Rodriguez T, Quigley DA. Why ARNT Prostate Tumors Responding to Enzalutamide? Cancer Discov. 2022 Sep 2;12(9):2017-2019. doi: 10.1158/2159-8290.CD-22-0702.

Reference Type DERIVED
PMID: 36052502 (View on PubMed)

Other Identifiers

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N14DAR

Identifier Type: -

Identifier Source: org_study_id