NERVES, NEUROBIOLOGY OF CANCER, NEUROLYSIS, PROSTATE CANCER
Conditions
Keywords
HIGH RISK LOCALIZED PROSTATE CANCER
Brief summary
The purpose of this research study is to assess whether inhibiting nerve activity to the prostate delays progression of disease in men with high-risk clinical features for prostate cancer. Prostate cancer has been shown to invade nerves, a mechanism that is thought to be involved in prostate cancer spread in men with high-risk cancer. When nerve activity to the prostate is blocked in mice with prostate cancer, prostate cancer growth and spread are inhibited. In a previous study we showed that doing so in humans was safe and may have anticancer therapeutic effect. In this study we will test whether one versus two injections of nerve blocking agent is more effective at reducing nerves in the prostate and whether it will slow/stop spread of prostate cancer after treatment.
Detailed description
Men with high-risk prostate cancer are at the greatest risk for clinical progression, with 22 to 40% developing metastatic disease within 10 years of initial treatment. Furthermore, the finding of perineural invasion (PNI) on pathology (when prostate cancer cells invade the nerves that innervate the prostate), is associated with higher Gleason grades and an approximate doubling in risk of lethal prostate cancer. As 90% of prostate cancer metastasis involve the bone marrow, and 97% of bone marrow metastasis involve the lumbar vertebrate from which the pre-ganglionic sympathetic nerves that innervate the prostate derive, targeting this neuro-anatomic connection between the prostate and its primary site of metastasis is an active area of investigation. Therefore, development of therapeutic strategies targeting nerves to prevent clinical progression after definitive therapy for prostate cancer are urgently needed. In a Phase 1a dose escalation study (NCT06703437) we recently demonstrated that periprostatic neurolysis with 5mL pure ethanol was well tolerated with no AEs. This resulted in an approximate 30% reduction in prostatic adrenergic nerve density. The goal of this study is to optimize prostatic denervation by comparing the denervation efficiency of 1 vs 2 periprostatic ethanol injections.
Interventions
PROCEDUREPeriprostatic neurolysis with dehydrated alcohol (ethanol)
Pre-operative ultrasound guided periprostatic neurolysis by injection of dehydrated alcohol
Sponsors
University of Texas Southwestern Medical Center
Urology Care Foundation
American Urological Association
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
High risk prostate cancer as defined by NCCN criteria Desires surgical disease treatment (radical prostatectomy) Surgical candidate (for radical prostatectomy) ≤cT3a on MRI No seminal vesicle, lymph node, or metastatic disease on PSMA PET No prior prostate cancer treatment (including androgen deprivation therapy, radiation therapy, focal therapy, cryo therapy)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Peritumoral adrenergic nerve density on final histology | 4 to 6 weeks after treatment initiation | Will quantify degree of neurolysis by measuring decrease in adrenergic nerve density on radical prostatectomy specimen histology |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in sexual health inventory for men (SHIM) score | 4 to 6 weeks after intervention | Change in erectile function as measured by SHIM score at enrollment and 4 to 6 weeks after periprostatic neurolysis |
| Change in International Prostate Symptom Score (IPSS) | 4 to 6 weeks after intervention | Change in lower urinary tract symptoms as measured by IPSS questionnaire at baseline and after neurolysis |
| Change in post prostatectomy penile length | 6months after surgery | Change in penile length post prostatectomy compared to baseline |
Countries
United States
Outcome results
None listed