The primary objective of this study is to further evaluate the safety and effectiveness of the MRI-guided TULSA-PRO device intended to ablate prostate tissue of patients with localized, organ-confined prostate cancer.
ID
Source
Brief title
Condition
- Reproductive neoplasms male malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
* Safety Endpoint: Frequency and severity of adverse events deemed related or
possibly related to the TULSA-PRO device, procedure, or ablative process will
be evaluated and reported in accordance with the Common Terminology Criteria
for Adverse Events (CTCAE) standard published by the National Cancer Institute
(NCI).
* Efficacy Endpoint: Prostate ablation efficacy will be evaluated using the
proportion of patients achieving a PSA nadir * 25% of the pre-treatment
baseline value.
Secondary outcome
* Adverse Event Endpoint: Frequency and severity of all adverse events,
described using the NCI CTCAE.
* Erectile Dysfunction Endpoint: Rate of erectile dysfunction, determined by
the change from baseline of the proportion of patients with erection firmness
sufficient for penetration (IIEF item 2 * 2).
* Urinary Incontinence Endpoint: Rate of urinary incontinence, determined by
the change from baseline of the proportion of patients who use one or more pads
per day (EPIC item 5 * 1).
* PSA Nadir Endpoint: Proportion of patients achieving PSA nadir * 0.5 ng/ml.
* PSA Stability Endpoint: Proportion of patients with PSA * 0.5 ng/ml at the
most recent follow-up visit.
* Prostate Volume Endpoint: Prostate volume reduction, evaluated on MRI between
the treatment day and 12-month follow-up visits.
* Prostate Biopsy Endpoint: Proportion of patients with negative prostate
biopsy at the 12-month follow-up visit, determined by TRUS-guided 10-core
biopsy.
* IPSS Endpoint: Change in International Prostate Symptom Score (IPSS), between
the baseline and most recent follow-up visit.
* IIEF Endpoint: Change in the Erectile Function, Orgasmic Function, Sexual
Desire, Intercourse Satisfaction and Overall Satisfaction domains of the
International Index of Erectile Function (IIEF-15), between the baseline and
most recent follow-up visit.
* EPIC Endpoint: Change in Urinary, Bowel, Sexual and Hormonal domains of the
Expanded Prostate Cancer Index Composite (EPIC), between the baseline and most
recent follow-up visit.
* Targeting Accuracy Endpoint: Conformal prostate ablation, measured
quantitatively between the target prostate volume and the target temperature
isotherm on MRI thermometry acquired during the TULSA-PRO procedure, and
described using three measures of targeting accuracy:
o Dice Similarity Coefficient (DSC * unitless from 0 to 1), is a statistical
validation metric to measure the degree of spatial overlap between two regions
[Dice 1945].
o Over- and under-targeted volumes (outside the target volume ± * voxel
margin), representing the amount of tissue * target temperature outside the
target volume and < target temperature inside the target volume, respectively.
The over- and under-targeted volumes are expressed in absolute cc, and as a %
of the target volume.
o Linear targeting in mm, representing the spatial accuracy (average) and
precision (standard deviation) of the TULSA-PRO to heat the target boundary to
the target temperature.
* CE-MRI Endpoint: Conformal prostate ablation, assessed qualitatively by
visualizing the peripheral region of enhancement surrounding the non-perfused
volume (NPV) on contrast-enhanced (CE)-MRI acquired immediately after treatment.
* mpMRI Endpoint: Characterize the effect of the TULSA-PRO ablation on
diagnostic multi-parametric prostate MRI (mpMRI), determined using PI-RADS v2
performed at the Baseline and 12-month follow-up visits.
Background summary
Prostate cancer is the most prevalent cancer among men in economically
developed countries, and is now recognized as one of the principal medical
problems facing the male population [GLOBOCAN 2008]. In Canada, prostate cancer
is the most frequently diagnosed cancer, with the number of cases expected to
double within the next 15 years, and is the second leading cause of
cancer-related death in men [Ellison and Wilkins 2009].
While conventional radical treatments for localized prostate cancer (surgery,
radiation therapy) provide good local control of disease, they leave many men
with significant long-term complications affecting urinary, bowel and sexual
function, which can reduce the patient*s quality of life significantly [Potosky
et al 2004, Thompson et al 2007]. This reduction in Quality of Life (QOL) is
becoming increasingly problematic as now younger men screened for the disease,
for whom continence and potency are of major concern, are faced with earlier
detection of less severe disease. The quandary faced is then how to proceed due
to a lack of intervention options that can treat the disease but not cause
substantial life-long side-effect issues.
As a result, men are seeking new ways to treat prostate cancer that allow them
to avoid surgery or radiation and their potential complications. In order to
address this shortcoming in the management of the disease, it is desirable to
offer treatments that can achieve good control of local disease, with low
morbidity.
Magnetic Resonance Imaging (MRI)-guided Transurethral Ultrasound Ablation
(MRI-TULSA) is a novel minimally-invasive technology to precisely ablate the
prostate gland using real-time MRI monitoring and active temperature feedback
control. High-energy ultrasound is delivered by a device inserted in the
urethra and is used to heat prostate tissue, both benign and malignant, to the
point of thermal coagulation (thermal ablation). MRI is used during the
procedure to measure in real-time the temperature distribution in the prostate,
enabling closed-loop feedback control of the heating pattern and precise
ablation of the prostate gland. MRI thermometry is based on a physical property
of water protons [Ishihara et al 1995], and has been demonstrated to control
ultrasound ablation by many groups [Vanne and Hynynen 2003, Mougenot et al
2009, Chopra et al 2012, Fuentes et al 2009]. In addition, MRI is used
pre-treatment to guide device positioning and perform treatment planning.
Post-treatment, Contrast Enhanced (CE)-MRI can be used to visualize the
Non-Perfused Volume (NPV) and assess the extent of thermal ablation.
Profound Medical Inc. (PMI) has developed an MRI-TULSA system, the TULSA-PRO,
which has the advantages of a non-invasive procedure with short treatment
times. The TULSA-PRO has the potential to offer accurate and precise prostate
ablation with low rates of complications and low morbidity.
Phase I clinical study of the TULSA-PRO in thirty prostate cancer patients has
demonstrated precise thermal ablation of the prostate gland with low rates of
serious or long-term adverse events, though with conservative safety margins
around the prostate capsule. The purpose of this Pivotal clinical study is to
establish the safety and effectiveness of the TULSA-PRO for accurate and
precise ablation of the prostate gland, with reduced safety margins and in a
larger prostate cancer population. In this Pivotal study, men with localized
(organ-confined) prostate cancer will undergo MRI-TULSA with the aim of
whole-gland prostate ablation. Patients will then be followed for twelve months
to check on the progress of the ablative therapy and associated adverse events,
monitor indicators of quality of life, and indicators of residual prostate
cancer. Additional patient monitoring for long-term effects will continue
annually for a period of up to five years after the MRI-TULSA procedure. This
study will provide confirmatory data that will become the basis for seeking
regulatory approval of the PMI TULSA-PRO in the USA.
Study objective
The primary objective of this study is to further evaluate the safety and
effectiveness of the MRI-guided TULSA-PRO device intended to ablate prostate
tissue of patients with localized, organ-confined prostate cancer.
Study design
Phase 1, single arm, international multicenter trial
Intervention
MRI-guided transurethral ultrasoundablation of the prostate.
Study burden and risks
Risks associated with the TULSA procedure:
The TULSA-PRO device has had limited testing in humans. The likelihood of the
risks below is estimated based on results of a 30-patient Phase I clinical
trial.
Likely (21% or more)
* Pain and inflammation in the pelvic area post-procedure
* Hematuria (blood in the urine)
* Urinary complications including increased urinary frequency and urgency
* Penile discharge or bleeding
* Retrograde (back into the bladder) or absence of or diminished ejaculation
* Urinary tract infection
* Reduced erectile function
Less Likely (5 * 20%)
* Post-ablation urinary retention after the supra-pubic catheter removal which
will require catheterization
* Bladder spasms
* Hematospermia (blood in the semen or ejaculation fluid)
* Bloating
* Erectile dysfunction (erection insufficient for penetration)
Rarely (less than 4%)
* Short term fever
* Stress incontinence (spontaneous urine passing with coughing or sneezing)
* Rectal discomfort or hemorrhoid pain
* Diarrhea
* Epididymitis (inflammation of the cord at the back of the testicle)
* Urethral stricture (narrowing of the tube you pass urine through)
* Urinary incontinence (uncontrolled leakage of urine)
* Osteitis pubis* (non-infectious inflammation of the pubic bone)
* Rectal wall injury and/or rectal fistula*
Yonge Street, Suite 4040 3080
Totonto, ON M4N 3N1
CA
Yonge Street, Suite 4040 3080
Totonto, ON M4N 3N1
CA
Listed location countries
Age
Inclusion criteria
Men diagnosed with biopsy-proven, organ-confined, low- to intermediate-risk prostate cancer will be eligible for participation in this study, provided they have not received prior treatment of their prostate cancer.
Exclusion criteria
Extraprostatic extension, lesion within 3mm of the urethra or sphincter plane, previous TURP, calcifications or cysts in the prostate, use of hormones
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 |
|---|---|
| CCMO | NL57803.091.16 |