Clinical trial NCT00681148: Botulinum Toxin Injection With Prostate Brachytherapy
Official title: Botulinum Toxin Injection With Prostate Brachytherapy: A Randomized, Placebo-controlled Study Monitoring Urinary Symptoms and PSA
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Prostate Cancer
Lower Urinary Tract Symptoms
Radioactive Seed Implantation
Keywords: Prostate specific antigen (PSA)
Prostate cancer
Lower urinary tract symptoms
Radioactive seed implantation
Lead sponsor: Emory University
Sponsor class: OTHER
First posted: 2008-05-21
Enrollment: 0
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to see if botox injection into the prostate during seed implantation (brachytherapy) for prostate cancer a) improves urinary symptoms or avoids need for urinary tract instrumentation over the 6-8 month post-operative period when one wants to avoid manipulating the radioactive seeds, and b) speeds up the drop in PSA. Patients will be randomized to botox vs saline injection, at the completion of the seed implantation procedure.

Detailed description: Brachytherapy is a popular treatment modality for localized prostate cancer, where radioactive seeds are implanted through 18 gauge needles into the prostate via a perineal template with rectal ultrasound guidance. The radioactivity is delivered over several months, depending on the isotope used. During this time, there can be exacerbation of urinary voiding symptoms from early edema of the prostate gland due to the implantation procedure, then later from the inflammatory reaction of the radiation. Because the initial acute inflammation may persist for many months despite steadily declining doses of radiation, attempts are made to minimize urinary symptoms prior to brachytherapy with pharmacologic therapy (alpha-blockers) or minimally invasive surgical therapy (transurethral incision or limited transurethral resection to avoid significant distortion of the prostate parenchyma for future seed implantation). Even with these precautions, around 30-40% of brachytherapy patients will still develop voiding symptoms. With such bothersome symptoms, intervention is deferred for at least 8-10 months to avoid distorting the planned field of radiation. Once symptoms develop, various additional pharmacologic measures are employed, such as increased doses of alpha-blockers, medrol steroid taper, and non-steroidal anti-inflammatory agents. Some patients require intermittent self-catheterization or suprapubic catheter for urinary diversion.

Botulinum toxin has been used for cosmetic uses, and has been successfully used for treatment of overactive bladder, external sphincter dyssynergia, and benign prostatic hyperplasia (BPH). The studies with BPH show reduction in symptoms scores, PSA, and prostate volume, the latter from atrophy due to the denervation effect. The response lasts for 6-9 months.

We propose to study botox intraprostatic injection during brachytherapy to see whether this improves urinary symptoms or avoids need for urinary tract instrumentation over this 6-8 month post-operative period when one wants to avoid manipulating the radioactive seeds. We will also monitor PSA, and see if there is any measurable augmentation of PSA decline with botox + Brachytherapy vs Brachytherapy alone. We will randomize patients to botox (100 units for \< 30 cc prostate; 200 units for \> 30 cc prostate) vs saline injection, administering 2 transperineal injections into both lateral lobes of the prostate (25-50 mg per injection), just 5-10 mm proximal to the bladder neck.

Study design:

N= 60 (30 receive Botox, 30 receive saline)

Followup:

AUA Symptoms scores weekly for 4 weeks, monthly thereafter Medications for urinary symptoms Need for catheterization PSA checked at 1 mo, 3 mo, 6 mo, 9 mo, 1 year, 15 mo, 18 mo, 24 mo

Eligibility criteria: Inclusion Criteria:

* Biopsy proven prostate cancer undergoing brachytherapy

Exclusion Criteria:

* Prior allergic reaction to botulinum toxin

Primary outcomes:
measure: Urinary symptoms
timeFrame: Weekly for 4 weeks, monthly thereafter until 1 year
Secondary outcomes:
measure: PSA
timeFrame: 1 mo, 3 mo, 6 mo, 9 mo, 1 year, 15 mo, 18 mo, 24 mo
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory Clinic, Emory University Hospital
state: Georgia
Study officials:
affiliation: Emory University SOM
name: Peter T Nieh, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lee WR, Hall MC, McQuellon RP, Case LD, McCullough DL. A prospective quality-of-life study in men with clinically localized prostate carcinoma treated with radical prostatectomy, external beam radiotherapy, or interstitial brachytherapy. Int J Radiat Oncol Biol Phys. 2001 Nov 1;51(3):614-23. doi: 10.1016/s0360-3016(01)01707-2.
citation: Wallner K, Merrick G, True L, Sutlief S, Cavanagh W, Butler W. 125I versus 103Pd for low-risk prostate cancer: preliminary PSA outcomes from a prospective randomized multicenter trial. Int J Radiat Oncol Biol Phys. 2003 Dec 1;57(5):1297-303. doi: 10.1016/s0360-3016(03)01448-2.
citation: Ansiaux R, Baudelet C, Cron GO, Segers J, Dessy C, Martinive P, De Wever J, Verrax J, Wauthier V, Beghein N, Gregoire V, Buc Calderon P, Feron O, Gallez B. Botulinum toxin potentiates cancer radiotherapy and chemotherapy. Clin Cancer Res. 2006 Feb 15;12(4):1276-83. doi: 10.1158/1078-0432.CCR-05-1222.
citation: Chuang YC, Chancellor MB. The application of botulinum toxin in the prostate. J Urol. 2006 Dec;176(6 Pt 1):2375-82. doi: 10.1016/j.juro.2006.07.127.
citation: Chuang YC, Huang CC, Kang HY, Chiang PH, Demiguel F, Yoshimura N, Chancellor MB. Novel action of botulinum toxin on the stromal and epithelial components of the prostate gland. J Urol. 2006 Mar;175(3 Pt 1):1158-63. doi: 10.1016/S0022-5347(05)00318-6.