Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 11 of 103 for:    "Kennedy disease"

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03297385
Recruitment Status : Completed
First Posted : September 29, 2017
Last Update Posted : September 29, 2017
Sponsor:
Collaborator:
Astellas Pharma Inc
Information provided by (Responsible Party):
The Netherlands Cancer Institute

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.


Condition or disease Intervention/treatment Phase
Prostate Cancer DNA Androgen Receptor Abnormal Drug: Enzalutamide Phase 2

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


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 50 participants
Intervention Model: Single Group Assignment
Intervention Model Description: 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.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Dynamics of Androgen Receptor Genomics and Transcriptomics After Neoadjuvant Androgen Ablation
Actual Study Start Date : August 28, 2014
Actual Primary Completion Date : April 1, 2017
Actual Study Completion Date : April 1, 2017

Resource links provided by the National Library of Medicine


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 Name: Xtandi




Primary Outcome Measures :
  1. 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.

  2. 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.


Secondary Outcome Measures :
  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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.

Layout table for additonal information
Responsible Party: The Netherlands Cancer Institute
ClinicalTrials.gov Identifier: NCT03297385     History of Changes
Other Study ID Numbers: N14DAR
First Posted: September 29, 2017    Key Record Dates
Last Update Posted: September 29, 2017
Last Verified: August 2017

Layout table for additional information
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

Keywords provided by The Netherlands Cancer Institute:
Prostate Cancer
Androgen Receptor Genomics
Enzalutamide
Prostatectomy
Neoadjuvant androgen ablation

Additional relevant MeSH terms:
Layout table for MeSH terms
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Androgens
Ascorbic Acid
Estrogens, Conjugated (USP)
Methyltestosterone
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Vitamins
Micronutrients
Nutrients
Growth Substances
Estrogens
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Anabolic Agents