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

Netherlands Cancer Institute (NKI)

Status and phase: Completed; Phase 2

Conditions: DNA; Prostate Cancer; Androgen Receptor Abnormal

Treatments: Drug: Enzalutamide

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03297385

N14DAR

Details and patient eligibility

About

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.

Full 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

Enrollment: 50 patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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50 participants in 1 patient group

Prostatectomy after enzalutamide

Experimental group

Description:

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.

Treatment:

Drug: Enzalutamide