Dynamics of Androgen Receptor Genomics and Transcriptomics After Neoadjuvant Androgen Ablation

NCT03297385 | Completed Phase 2

• 1 other identifier: N14DAR
• Study Type: interventional
• Target: 50
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Prostate Cancer; DNA; Androgen Receptor Abnormal

Keywords

Prostate Cancer; Androgen Receptor Genomics; Enzalutamide; Prostatectomy; Neoadjuvant androgen ablation

Outcome Measures

Primary Outcomes (2)

• 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).

• 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 Outcomes (5)

• Clinical down-staging of enzalutamide pretreatment

  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

  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

  From baseline (prior to treatment), until disease progression or as long as treatment is tolerated or until study completion (60 months).

• Gleason grading

  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).

  From baseline (prior to treatment), until disease progression or as long as treatment is tolerated or until study completion (60 months).

Study Arms (1)

Prostatectomy after enzalutamide

EXPERIMENTAL

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

Interventions

Enzalutamide 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.

Also known as: Xtandi

Prostatectomy after enzalutamide

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men over 18 years of age.
• clinically non-metastasized prostate cancer, tumor that can be imaged (TRUS or MRI) in order to allow for accurate preoperative biopsies.
• Gleason score 7-10
• written informed consent
• WHO performance 0-1

You may not qualify if:

• A history of seizures.
• Clinically nodal metastases.
• Prostatitis or urinary tract infection.
• Tumor of the prostate that can not be visualized by TRUS or MRI.

Sponsors & Collaborators

• The Netherlands Cancer Institute: lead
• Astellas Pharma Inc: collaborator

Related Publications (1)

• 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.

  PMID: 36052502 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

enzalutamide

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: April 13, 2017
• First Posted: September 29, 2017
• Study Start: August 28, 2014
• Primary Completion: April 1, 2017
• Study Completion: April 1, 2017
• Last Updated: September 29, 2017

Record last verified: 2017-08