1. To assess the effects of 3 months neoadjuvant androgen ablation with enzalutamide on the surgicial margin status of men with non-metastasized prostate cancer.2. To properly evaluate the effects of androgen ablation on gene expression, analyses of…
ID
Source
Brief title
Condition
- Reproductive neoplasms male malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary Objective:
1. to evaluate whether 3 months neoadjuvant androgen ablation with enzalutamide
can reduce the surgicial positive margin rate of men with non-metastasized
prostate cancer.
2. Analyse the effects of short term (3 months) enzalutamide on distinct
AR-chromatin binding patterns in correlation with tissue proliferation in
normal prostate tissue and prostate cancer.
Secondary outcome
Secondary Objective(s):
= To assess the effects of 3 months enzalutamide pretreatment on down-staging
= Study the correlation between AR-chromatin binding alterations and Ki-67
expression.
= Compare the AR-chromatin binding with expression alterations of known
AR-dependent genes such as PSA, human kallikrein and PSMA.
= Compare AR-chromatin binding patterns with gleason grading.
= Confirm findings of associated genes on TMA derived from prostatectomy
specimens.
Background summary
To evaluate the tumor cell proliferation, AR activity, gene expression patters
and AR chromatin binding after a short course of antiandrogen enzalutamide
treatment, we will obtain biopsy material prior before and after 3 months
treatment. Simultaneously we will study the tumor downsizing effects of 3
months of enzalutamide. AR ChIP-sequencing analyses will be used to identify
direct AR target genes specifically affected by enzalutamide antiandrogen
therapy in both tumor and normal prostatic tissue, in order to identify
predictive signatures for treatment response.
Study objective
1. To assess the effects of 3 months neoadjuvant androgen ablation with
enzalutamide on the surgicial margin status of men with non-metastasized
prostate cancer.
2. To properly evaluate the effects of androgen ablation on gene expression,
analyses of samples from the same patient before and after androgen ablation
are essential. For this reason, we will study the alterations in transcription
factor/chromatin interaction of AR in the individual patient by performed
pretreatment and postreatment sampling.
Study design
In this study enzalutamide will be administered for a period of 3 months prior
to prostatectomy. Early studies on neoadjuvant therapy did show an improvement
in perioperative outcome such as positive margin rate and blood loss but
randomized comparisons failed to show a benefit for overall survival after
prostatectomy, although subgroup analysis suggested that men with higher grade
lesions may have improved biochemical free survival
Intervention
1. tumor directed prostate biopsies
2. 3 months of neoadjuvant enzalutamide treatment
Study 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 will 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. The surgical
procedure will be postponed for an estimated 4 weeks considering the already
present waiting list for the procedure.
plesmanlaan 121
Amsterdam 1066 CX
NL
plesmanlaan 121
Amsterdam 1066 CX
NL
Listed location countries
Age
Inclusion criteria
1. Men over 18 years of age.
2. non-metastasized prostate cancer, visible on transrectal ultrasound or MRI planned for prostatectomy
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
Androgen ablative therapy within 6 weeks of inclusion (including 5 alpha-reductase inhibitors)
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2014-000476-26-NL |
| CCMO | NL47463.031.14 |