Prostate Cancer
Conditions
Brief summary
This pilot randomized, single-blind, placebo-controlled study evaluates the feasibility, safety, and preliminary biological activity of neoadjuvant intraprostatic onabotulinumtoxinA (BOTOX®) administered before radical prostatectomy in men with high-risk localized prostate cancer. Thirty participants will be randomized 1:1 to receive a single transrectal ultrasound-guided intraprostatic injection of onabotulinumtoxinA (50 units) or placebo 6 to 8 weeks before surgery. Outcomes include feasibility metrics, safety, adverse events, pathological findings at prostatectomy, and postoperative prostate-specific antigen (PSA) levels
Detailed description
High-risk localized prostate cancer is associated with a substantial risk of adverse pathological features and disease recurrence despite definitive treatment with radical prostatectomy. Emerging evidence suggests that neural signaling within the prostate tumor microenvironment contributes to tumor growth, progression, and treatment resistance. OnabotulinumtoxinA (BOTOX®), a neurotoxin that blocks acetylcholine release, has demonstrated biological effects in prostate tissue and may provide a novel approach to modulating tumor-associated neural pathways. This single-center, prospective, randomized, single-blind, placebo-controlled pilot study will enroll 30 men with high-risk or very-high-risk localized prostate adenocarcinoma who are scheduled to undergo radical prostatectomy. Participants will be randomized in a 1:1 ratio to receive either a single transrectal ultrasound-guided intraprostatic injection of onabotulinumtoxinA (50 units) or an equivalent-volume normal saline placebo 6 to 8 weeks prior to surgery. Participants will remain blinded to treatment assignment. The primary objective is to evaluate study feasibility and safety, including participant accrual, protocol adherence, successful completion of intraprostatic injection and planned surgery, and the incidence and severity of adverse events. Secondary objectives include evaluation of pathological outcomes at prostatectomy, including Gleason score, perineural invasion, stromogenic component, tumor burden, pathological stage, and surgical margin status. Early postoperative PSA outcomes will also be assessed. Exploratory analyses will evaluate time to biochemical recurrence following radical prostatectomy. This pilot study is not powered to demonstrate clinical efficacy. Instead, it is designed to establish the safety and feasibility of neoadjuvant intraprostatic onabotulinumtoxinA and generate preliminary biological and pathological data to support future studies investigating neural modulation as a therapeutic strategy in prostate cancer.
Interventions
A single transperineal, transrectal ultrasound (TRUS)-guided intraprostatic injection of onabotulinumtoxinA, total dose 50 units, administered 6 to 8 weeks prior to radical prostatectomy.
OTHERNormal Saline Placebo
Participants randomized to the placebo arm will receive a single transperineal, transrectal ultrasound (TRUS)-guided intraprostatic injection of normal saline administered in an identical volume and injection pattern as the active treatment arm, 6 to 8 weeks prior to planned radical prostatectomy.
Sponsors
The Methodist Hospital Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Masking description
Participant will not know if they are receiving Botox or placebo, they will remain blinded.
Intervention model description
Participants will be randomized in a 1:1 ratio to receive either a single intraprostatic injection of onabotulinumtoxinA (50 units) or placebo (normal saline) administered 6 to 8 weeks prior to radical prostatectomy. Participants remain in their assigned treatment group throughout the study, and outcomes are compared between parallel treatment arms.
Eligibility
Sex/Gender
MALE
Age
45 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Male, ≥ 45 years * Histologically confirmed prostate adenocarcinoma * Gleason score ≥8 on biopsy * Candidate for and scheduled to undergo RALP for primary treatment * ECOG 0-2 * Able to read, speak, and understand English * Able to provide informed consent
Exclusion criteria
* Prior prostate cancer therapy (radiation, ADT, chemotherapy) * Metastatic disease * Known hypersensitivity to botulinum toxin * Neuromuscular disorders (e.g., myasthenia gravis) * Active infection, coagulopathy, or contraindication to transperineal injection * Medications significantly affecting neuromuscular transmission (clinically relevant) * Any condition compromising safety or protocol compliance
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Successful Completion of Planned Radical Prostatectomy | Within 6 to 8 weeks after intraprostatic injection. | Proportion of participants who undergo planned radical prostatectomy following study intervention without study-related cancellation or unacceptable delay. |
| Participant Accrural | Through study completion, an average of 1 year | Number of participants enrolled in the study |
| Protocol Adherence | Through study completion, an average of 1 year | Proportion of participants who complete study procedures according to protocol requirements. |
| Successful Completion of Intraprostatic Injection | At time of surgery | Number of participants who successfully receive the assigned intraprostatic study injection. |
| Incidence of Adverse Events | From study injection through 36 months of follow-up. | Incidence, severity, seriousness, and relationship of adverse events associated with intraprostatic administration of onabotulinumtoxinA or placebo. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Positive Surgical Margin Status | At radical prostatectomy (6 to 8 weeks after study injection). | Proportion of participants with positive surgical margins following radical prostatectomy. |
| Tumor Size | At radical prostatectomy (6 to 8 weeks after study injection). | Tumor size measured in radical prostatectomy specimens. The measurement will be recorded in centimeters (cm). |
| Postoperative Prostate-Specific Antigen (PSA) | 6 to 8 weeks after radical prostatectomy and during follow-up through 36 months. | Serum PSA levels following radical prostatectomy. |
| Gleason Score at Radical Prostatectomy | At radical prostatectomy (6 to 8 weeks after study injection). | Comparison of Gleason score determined from radical prostatectomy specimens between treatment arms. Gleason Score determined from radical prostatectomy specimens. Gleason Scores range from 6 to 10, with higher scores indicating more aggressive prostate cancer. |
| Perineural Invasion | At radical prostatectomy (6 to 8 weeks after study injection). | Presence and extent of perineural invasion identified in radical prostatectomy specimens. |
| Stromogenic Component | At radical prostatectomy (6 to 8 weeks after study injection). | Assessment of stromogenic component in radical prostatectomy specimens. |
Countries
United States
Contacts
CONTACTVivian MacDonnell, MD
CONTACTBrian Miles, MD
PRINCIPAL_INVESTIGATORBrian Miles, MD
Houston Methodist Urology, Houston Methodist Research Institute
Outcome results
None listed