Prostate CancerPhase 2DARANANCT03297385
Dynamics of Androgen Receptor Genomics and Transcriptomics After Neoadjuvant Androgen Ablation
A Phase 2 study testing Enzalutamide in people with Prostate Cancer and DNA, run by The Netherlands Cancer Institute.
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. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostate Cancer, DNA, Androgen Receptor Abnormal
- What is being tested?
- Enzalutamide
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- No sites listed yet
- Study dates
- 28 Aug 2014to 1 Apr 2017
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- A history of seizures.
- Clinically nodal metastases.
- Prostatitis or urinary tract infection.
- Androgen ablative therapy within 6 weeks of inclusion (including 5 alpha-reductase inhibitors).
- Tumor of the prostate that can not be visualized by TRUS or MRI.
About this study
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.
Read the 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
- Conditions
- Prostate Cancer, DNA, Androgen Receptor Abnormal
- Being tested
- Enzalutamide
- Keywords
- Prostate Cancer, Androgen Receptor Genomics, Enzalutamide, Prostatectomy, Neoadjuvant androgen ablation
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EnzalutamideDrug
Also called Xtandi
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 group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Enzalutamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Effects of enzalutamide on tumor downstaging
To study the effects of enzalutamide on surgical margin status and AR / DNA interaction and gene expression.
Measured: 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.
Measured: 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
To assess the effects of 3 months enzalutamide pretreatment on clinical down-staging
Measured: 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
Study the correlation between AR-chromatin binding alterations and Ki-67 expression.
Measured: 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
Compare the AR-chromatin binding with expression alterations of known AR-dependent genes such as PSA, human kallikrein and PSMA.
Measured: From baseline (prior to treatment), until disease progression or as long as treatment is tolerated or until study completion (60 months).
Gleason grading
Compare AR-chromatin binding patterns with Gleason grading.
Measured: 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).
Find associated genes on TMA derived from prostatectomy specimens.
Measured: From baseline (prior to treatment), until disease progression or as long as treatment is tolerated or until study completion (60 months).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Sep 2017
- Study start28 Aug 2014
- Primary completion1 Apr 2017
- Study completion1 Apr 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- More trials run by The Netherlands Cancer InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- 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)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Netherlands Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Astellas Pharma Inc
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03297385
- Sponsor's protocol ID
- N14DAR
- Acronym
- DARANA
- Status last verified
- Aug 2017
- First submitted
- 13 Apr 2017
- Last updated
- 29 Sep 2017
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 36052502
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dynamics of Androgen Receptor Genomics and Transcriptomics After Neoadjuvant Androgen Ablation
- ClinicalTrials.gov ID
- NCT03297385
- Acronym / sponsor ID
- DARANA / N14DAR
- Conditions
- Prostate Cancer, DNA, Androgen Receptor Abnormal
- Keywords
- Prostate Cancer, Androgen Receptor Genomics, Enzalutamide, Prostatectomy, Neoadjuvant androgen ablation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- The Netherlands Cancer InstituteUniversity, hospital or other
- Collaborators
- Astellas Pharma Inc
- Study start
- 28 Aug 2014 (actual)
- Primary completion
- 1 Apr 2017 (actual)
- Study completion
- 1 Apr 2017 (actual)
- First posted
- 29 Sep 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- 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.
| Arm | Type | Receives |
|---|---|---|
| Prostatectomy after enzalutamide | Experimental | Drug: EnzalutamideThis 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (5 listed)
- A history of seizures.
- Clinically nodal metastases.
- Prostatitis or urinary tract infection.
- Androgen ablative therapy within 6 weeks of inclusion (including 5 alpha-reductase inhibitors).
- Tumor of the prostate that can not be visualized by TRUS or MRI.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EnzalutamideAlso: XtandiMen 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. | Drug | Prostatectomy after enzalutamide |
Primary outcome
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.
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.
5 secondary outcomes
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).
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).
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).
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).
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).
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2017.
- Derived from this study: PubMed 36052502Zhang 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.
Related trials for Prostate Cancer
Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
Active, not recruitingObservational study
MRI Fusion Biopsy vs. Micro-Ultrasound Guided Biopsy
Prostate Cancer
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
Not yet recruitingPhase 1/2
STAR0602 With Nivolumab in Non Small Cell Lung Cancer and in Metastatic Castrate-Resistant Prostate Cancer, and STAR0602 Alone in Thymic Carcinoma
NSCLC, Non-Small Cell Lung Cancer
Recruiting
Rehabilitation and Sex Therapy to Optimize Recovery After Prostate Cancer Treatment
Prostate Cancer, Urinary Incontinence
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Enzalutamide in people with Prostate Cancer and DNA, run by The Netherlands Cancer Institute.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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).). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03297385, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Sep 2017.