Dynamics of Androgen Receptor Genomics and Transcriptomics After Neoadjuvant Androgen Ablation (DARANA)

September 28, 2017 updated by: The Netherlands Cancer Institute

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed 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

Study Type

Interventional

Enrollment (Actual)

50

Phase

  • Phase 2

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: 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.
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.
Other Names:
  • Xtandi

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Effects of enzalutamide on tumor downstaging
Time Frame: From baseline (prior to treatment), until disease progression or as long as treatment is tolerated or until study completion (60 months).
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
Time Frame: From baseline (prior to treatment), until disease progression or as long as treatment is tolerated or until study completion (60 months).
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical down-staging of enzalutamide pretreatment
Time Frame: From baseline (prior to treatment), until disease progression or as long as treatment is tolerated or until study completion (60 months).
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).
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).
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).
AR-dependant 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).
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).
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).
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).
Find associated genes in prostate tissue, using tissue microarray (TMA).
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 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).

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The Netherlands Cancer Institute

Collaborators

Astellas Pharma Inc

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

August 28, 2014

Primary Completion (ACTUAL)

April 1, 2017

Study Completion (ACTUAL)

April 1, 2017

Study Registration Dates

First Submitted

April 13, 2017

First Submitted That Met QC Criteria

September 28, 2017

First Posted (ACTUAL)

September 29, 2017

Study Record Updates

Last Update Posted (ACTUAL)

September 29, 2017

Last Update Submitted That Met QC Criteria

September 28, 2017

Last Verified

August 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • N14DAR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Prostate Cancer

Clinical Trials on Enzalutamide

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Belarus

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe