Prostate Cancer IRE Study (PRIS)

Prostate Cancer Clinical Trial

— PRIS  

Official title:

Prostate Cancer IRE Study (PRIS) - A Randomized Controlled Trial Comparing Focal to Radical Treatment in Localized Prostate Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05513443
• Other study ID #: K2021-4853
• Secondary ID: 4-1421/2022
• Status: Recruiting
• Phase: N/A
• Start date: September 1, 2022
• Est. completion date: September 1, 2025

Study information

• Verified date: March 2023
• Source: Karolinska Institutet
• Contact: Anna Lantz, Ass Prof
• Phone: +46851770000
• Email: anna.lantz[@]regionstockholm.se
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of this study is to evaluate the feasibility to treat localized prostate cancer diagnosed with MRI and targeted/systematic biopsies, with IRE in comparison with conventional radical treatments with the primary objective to locally control the tumour with a minimum of side effects.

Description:

OBJECTIVES The aim of the proposed research is to evaluate the cancer control, genitourinary, rectal and overall health-related quality of life outcomes of focal therapy for unifocal localized prostate cancer using irreversible electroporation (IRE).

PRIMARY AIM

• To evaluate functional outcomes in men treated for unifocal ISUP 2-3 localized prostate cancer with focal treatment in comparison to conventional treatment with either radical prostatectomy or radiation therapy

SECONDARY AIMS

• To evaluate adverse events in men treated for unilfocal ISUP 2-3 localized prostate cancer with focal treatment in comparison to conventional treatment with either radical prostatectomy or radiation therapy

• To evaluate progression free and treatment free survival in men treated for unifocal ISUP 2-3 localized prostate cancer with focal treatment in comparison to conventional treatment with either radical prostatectomy or radiation therapy

• Economic evaluation of each technique

TRIAL DESIGN This study is a randomized controlled exploratory trial comparing focal therapy to conventional radical treatment of prostate cancer with the primary aim to evaluate functional outcomes 12 months after treatment.

Patients will be included from 4 different hospitals within the Stockholm County; Karolinska University Hospital, Danderyd Hospital, St Görans Hospital, Södersjukhuset. Eligible patients, after MRI and targeted/systematic biopsies, will be men with clinically significant intermediate-risk PCa or dominant unifocal clinically significant intermediate-risk and small contralateral low-risk disease without previous history of prostate cancer treatment.

Potential study participants will have a visit scheduled together with an urologist and oncologist, where a treatment decision of radical prostatectomy or radiation therapy will be done together with the patient. At this visit the patient will receive oral and written information about the study. If the patient is interested in participating, a baseline visit is scheduled during which informed consent is obtained and the patient randomized to one of two standard treatments or focal treatment.

Patients eligible for radical prostatectomy will be randomized in study 1 to focal treatment or radical prostatectomy. Patients eligible for radiation therapy will be randomized in study 2 to focal treatment or radiation therapy. Time between randomization and treatment will be <= 6 weeks.

Patients will be asked to fill out study specific questionnaires with questions on functional outcomes and quality of life.

Main outcome measurement in study 1 will be urinary incontinence at 12 months post treatment and in study 2 irritative urinary symptoms 12 months post treatment. Further outcomes will be erectile dysfunction, adverse events, progression-free and treatment-free survival.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 184
• Est. completion date: September 1, 2025
• Est. primary completion date: September 1, 2024
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 40 Years and older

Eligibility

Inclusion Criteria:

• Age at inclusion = 40 years

• MRI-visible lesion

• EPE 3* <1.5 cubic cm3 lesion volume

• Gleason score 3 + 4 or 4 + 3 from a single MRI-visible lesion without any Gleason grade 4 in systematic biopsies outside of the target

• PSA level = 20 ng/ml

• Clinical stage = T2c disease

• Unifocal significant disease

• Life expectancy of = 10 years

• Sufficient proficiency in the Swedish language to understand written and verbal information about the trial, its consent process and the study questionnaires

• Extraprostatic extension; 5-grade Likert scale 1=

Exclusion Criteria:

• Intraductal tumour

• History of treatment for prostate cancer; surgery, radiation, chemotherapy or hormonal treatment

• History of cardiac arrythmias

• Pacemaker

• Renal insufficiency; GFR<30

• Severe illnesses such as concomitant cancers, severe cardio-vascular disease or dementia

• Contraindications for magnetic resonance imaging (MRI) e.g. magnetic cerebral clips, cochlear implants or severe claustrophobia

• History of bladder cancer

• History of previous pelvic radiotherapy

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Procedure:
• Irreversible electroporation, IRE
IRE involves the use of high voltage electrical pulses to treat solid tumors by increasing membrane permeability and inducing membrane disruption, leading to cell death. The technique is used in Sweden today in radical ablative therapies in the treatment of tumors in the liver, kidney and pancreas. Prior to treatment a Foley catheter is placed. During the treatment, which takes place under anesthesia, the patient is placed in gynecological position and the tumour lesion is located with BK transrectal fusion ultrasound. Thereafter the needles are placed transperineal around the tumor in the prostate using a brachytherapy grid (17Ga Civco brachytherapy grid), guided by the ultrasound/MRI fusion images. Through the needles electrical pulses are then sent to treat the tumor in the center using the Nanoknife technique. After treatment patients are treated with diuretics to flush the kidneys post treatment.
• Radical prostatectomy
Radical prostatectomy

Radiation:
• Radiation therapy
Radiation therapy for prostate cancer

Locations

Country	Name	City	State
Sweden	Karolinska Institutet	Stockholm	Solna

Sponsors (2)

Lead Sponsor	Collaborator
Karolinska Institutet	Karolinska University Hospital

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Primary outcome in PRIS 1: Urinary continence	Urinary incontinence defined by Q3 in EPIC-26, =1 pad/day ("Yes") versus none ("No")	12 months postoperatively
Primary	Primary outcome in PRIS 2: Irritative urinary symptoms	Irritative urinary symptoms defined by Q4e in EPIC-26, Moderate/big problem ("Yes") Versus no/small problem ("No")	12 months postoperatively
Secondary	Erectile dyfunction	IIEF score: International Index of Erectile Function, change. The possible scores for the IIEF-5 range from 5 to 25, and ED was classified into five categories based on the scores: severe (5-7), moderate (8-11), mild to moderate (12-16), mild (17-21), and no ED (22-25).	12 months postoperatively
Secondary	Voiding function	International Prostate Symptom Score (IPSS score), change. It is a validated, reproducible scoring system to assess disease severity and response to therapy. The IPSS is made up of 7 questions related to voiding symptoms. A score of 0 to 7 indicates mild symptoms, 8 to 19 indicates moderate symptoms and 20 to 35 indicates severe symptoms.	12 months postoperatively
Secondary	Bowel function	Expanded Prostate Cancer Index, EPIC-26, Q6 change in score. The EPIC-26 is a validated instrument that measures health-related quality of life across 5 PCa-specific domains. Consequently, the minimum symptom score (best HRQOL) = 0 and the maximum symptom score (worst HRQOL) = 12 in each domain. For consistency, the values assigned to each question range from 0 (best) to 4 (worst) regardless of whether there were 4 or 5 response options per question.	12 months postoperatively
Secondary	Adverse events	Clavien-Dindo	3 months postoperatively
Secondary	Quality of life, EuroQoL-5 Dimensions	EQ5D; The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems.	12 months postoperatively
Secondary	Treatment Failure, experimental arms	Need for additional focal or whole gland treatment or ADT; Need for whole gland treatment or ADT; Need for whole gland treatment or ADT or ISUP 2 at 12 mo biopsy	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Secondary	Treatment Failure, control arm (surgery)	Post-operative PSA =0.2 ng/ml or adjuvant treatments including ADT	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Secondary	Treatment Failure, control arm (radiation)	PSA >2 over nadir (Phoenix) or adjuvant treatments including ADT	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months