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Trial registered on ANZCTR


Registration number
ACTRN12617000806369
Ethics application status
Approved
Date submitted
26/05/2017
Date registered
2/06/2017
Date last updated
8/02/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
A pilot study evaluating focal irreversible electroporation as treatment for participants with recurrent prostate cancer after radiotherapy.
Scientific title
Focal irreversible electroporation as salvage treatment in radio-recurrent prostate cancer: a prospective multi-centre pilot study
Secondary ID [1] 292040 0
CT-2017_CTN-01330_1 v1 Therapeutic Goods Administration Australia
Universal Trial Number (UTN)
Trial acronym
FIRE study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Recurrent Prostate Cancer 303440 0
Condition category
Condition code
Cancer 302848 302848 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The NanoKnife (Registered Trademark) System with six outputs is indicated for the surgical ablation of soft tissue. It has FDA approval [510(k) Number: K080376]. Intended use in this study is to treat radio-recurrent prostate cancer.
Patients will receive general anaesthesia, followed by intravenous muscle paralysis, a single-shot antibiotic prophylaxis and the insertion of an indwelling urethral catheter.
Up to 6 Needle-like electrode probes are then placed around the tumour using transrectal ultrasound for guidance during the insertion through the perineum with a 5x5 mm brachytherapy template grid.. The placement of the electrodes aims for focal ablation of the tumour. This will include a circumferential safety margin of at least 5mm whilst still being mindful of nearby vital structures. Technical considerations include spacing of the electrodes (required to be 10mm to 20mm apart), and an average electrode exposure length per needle of 15mm. The number of electrodes required for each patient is dependent on the volume of tissue to be ablated and will be determined by the treating clinician before the procedure.
The Nanoknife system is then programmed to start with 10 pulses per electrode-pair with pulse length set to 90 microseconds and intensity of 1500 V per cm. Treatment delivery is then automatically calculated by the system on the basis of the number of electrodes inserted, the respective distances between each electrode and the active electrode length to obtain an optimal electrical field of between 20A and 40A. If the current does not reach the minimum of 20 amps between one or more electrode-pairs, the voltage will have to be increased with 10 percent for that particular electrode-pair. Following the initial 10 pulses, the subsequent 80 pulses will be delivered to achieve a total of 90 pulses.
The total procedure time is estimated to be 1 hour, starting with the administration of general anaesthesia. The actual Nanoknife procedure will take around 30min.
A Urologist, the coordinating investigator (CI), will perform the procedure once as day surgery at St Vincent’s Private Hospital. The CI has a great expertise in the treatment of prostate cancer in Australia and has 4 years experience conducting the procedure, primarily in the setting of primary prostate cancer.
Adherence of the intervention is assessed by the treating Urologist. In addition a second medical doctor or nurse is present during the procedure to ensure settings and adjustments are correctly entered in the Nanoknife system. A procedural template will be filled out during the procedure to help with accurate recording of all settings and adjustments made during procedure.
Intervention code [1] 298168 0
Treatment: Devices
Intervention code [2] 298223 0
Treatment: Surgery
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 302242 0
Safety profile of salvage focal irreversible electroporation (IRE) in radio-recurrent disease will be recorded using the the National Cancer Institute common terminology criteria for adverse events (CTCAE Version 4.0 classification system).
Timepoint [1] 302242 0
During the procedure and at 3, 6 and 12 month after the procedure
Primary outcome [2] 302243 0
Quality of life outcomes as assessed by the EPIC-AUA-SF12-2 questionnaire.
Timepoint [2] 302243 0
Before the procedure as Baseline and at 3, 6 and 12 month after the procedure.
Primary outcome [3] 302310 0
Urinary functional outcome as assessed by the EPIC-AUA-SF12-2 questionnaire
Timepoint [3] 302310 0
Before the procedure as Baseline and at 3, 6 and 12 month after the procedure
Secondary outcome [1] 335262 0
Presence of cancer based on TTMB mapping biopsy

Timepoint [1] 335262 0
one-year post treatment
Secondary outcome [2] 335263 0
Presence of cancer based on mpMRI
Timepoint [2] 335263 0
6 month post treatment
Secondary outcome [3] 335433 0
As additional primary outcome the sexual functional outcomes will be assessed as by the EPIC-AUA-SF12-2 questionnaire adapted to include the IIEF (index of erectile function)
Timepoint [3] 335433 0
Before the procedure as Baseline and at 3, 6 and 12 month after the procedure

Eligibility
Key inclusion criteria
1. Patients with radio-recurrent PCa greater or equal than 2 years post LDR or PDR or HDR brachytherapy or external beam radiation therapy
2. Imaging negative for metastatic disease
3. Radiological stage T1 to T3aN0M0 disease
4. Lesion visible on mpMRI with good biopsy co-registration
5. Histologically proven Gleason 7 to 10 PCa
6. PCa recurrence limited to a single lesion in the prostate as indicated by pre-operative mpMRI and biopsy
7. PSA smaller than 10 ng per mL
8. Fulfil Phoenix criteria (Nadir plus 2)
9. Life expectancy: 10 years or more
10. Able to provide written consent
Minimum age
18 Years
Maximum age
No limit
Gender
Males
Can healthy volunteers participate?
No
Key exclusion criteria
1. Biopsy proven lymph node involvement
2. Metastatic disease
3. Bowel disease (e.g. IBD)
4. Previous transurethral resection of the prostate (TURP)
5. Major medical or psychiatric illness, which in the investigator’s opinion, would prevent completion of treatment and/or follow-up
6. Inability to undergo mpMRI
6a. Incompatible metallic implants
6b. Claustrophobia
7. Men unable to tolerate transrectal ultrasound
8. Men who have undergone previous focal therapy to the prostate (HIFU, IRE, cryosurgery, thermal, microwave, laser therapy)
9. Men who have received androgen suppression/hormone treatment within the last 6 months
10. Metallic implants or stents in urethra
11. Histological evidence of any cancer in more than one area of the prostate
12. Requires simultaneous urological procedure at time of salvage IRE (e.g. mini TUR)

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Since it is a pilot-study, the sample size of 40 (10 per participating centre) is based on similar salvage pilot-studies performed with other focal therapy techniques. The comprehensive review of Smit Duijzenkunst et al.(World J Urol. 2016. doi:10.1007/s00345-016-1811-9) shows samples size ranging from 15 to 91 patients with an average of 33.

The rate of disease recurrence at 1 year, as well as the adverse events rates will be recorded as an absolute proportion.
The functional outcomes before and after the procedure will be compared using a paired sample t-test or Wilcoxon signed-ranks test, depending on the distribution.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 8122 0
St Vincent's Private Hospital (Darlinghurst) - Darlinghurst
Recruitment postcode(s) [1] 16182 0
2010 - Darlinghurst

Funding & Sponsors
Funding source category [1] 296572 0
Other
Name [1] 296572 0
St. Vincent's Prostate Cancer Centre
Address [1] 296572 0
Suite 508, Level 5, 438 Victoria Street, Darlinghurst NSW 2010
Country [1] 296572 0
Australia
Primary sponsor type
Hospital
Name
St. Vincent’s Private Hospital
Address
406 Victoria St, Darlinghurst NSW 2010
Country
Australia
Secondary sponsor category [1] 295526 0
None
Name [1] 295526 0
Address [1] 295526 0
Country [1] 295526 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297789 0
St Vincent’s Human Research Ethics Committee
Ethics committee address [1] 297789 0
St Vincent’s Hospital Research Office, Translational Research Centre , 97-105 Boundary Street, Darlinghurst NSW 2010
Ethics committee country [1] 297789 0
Australia
Date submitted for ethics approval [1] 297789 0
13/10/2016
Approval date [1] 297789 0
06/12/2016
Ethics approval number [1] 297789 0
SVH16/191

Summary
Brief summary
This study aims to assess the safety profile and functional outcomes of salvage focal irreversible electroporation (IRE) in patients with prostate cancer.

Who is it for?
You may be eligible to join this study if you are aged 18 years or above and have been diagnosed with local recurrent prostate cancer after radiotherapy (radio-recurrent prostate cancer) without metastatic disease.

Study details
All participants in this study will undergo a procedure known as salvage focal irreversible electroporation (IRE) as day surgery at St Vincent’s Private Hospital. The procedure is conducted under general anaesthesia and involves insertion of up to 6 needle-like electrode probes around the tumour. Microsecond electrical probes are then delivered to the tumour area to cause cell death and destroy the tumour. The procedure is conducted by a urologist and takes approximately 60 minutes.

Participants will be monitored for safety throughout the procedure, and at 3, 6 and 12 months after the procedure. They will also be asked to complete questionnaires at these time points to assess quality of life and urinary and sexual functional outcomes. Cancer recurrence will also be assessed at 6 month and at one year post treatment.

The results of this trial will build on a currently developing evidence base in order to guide the judicious use of IRE in patients with localised, radio-recurrent prostate cancer.
Trial website
Trial related presentations / publications
Public notes
(A) Sites can be added on.
To increase the target size to a total of 40, which is needed for statistical power of the study.
Each site will be responsible for their own primary sponsor and their own funding.
Additional sites:
1. Academic Medical Hospital, Amsterdam, The Netherlands
2. Memorial Sloan Kettering Cancer Centre, New York, USA
3. Grace Hospital, Tauranga, New Zealand

(B) Definition: exclusion criteria no 11; we define an area as quadrant.

Contacts
Principal investigator
Name 75118 0
Prof Phillip Stricker
Address 75118 0
Suite 1001, Level10, St Vincent’s Clinic, 438 Victoria St., Darlinghurst NSW 2010
Country 75118 0
Australia
Phone 75118 0
+61 2 8382 6971
Fax 75118 0
Email 75118 0
phillip@stricker.com.au
Contact person for public queries
Name 75119 0
Ms Anne-Maree Haynes
Address 75119 0
Garvan Institute of Medical Research and The Kinghorn Cancer Centre, 370 Victoria St., Darlinghurst NSW 2010
Country 75119 0
Australia
Phone 75119 0
+61 2 9355 5786
Fax 75119 0
Email 75119 0
a.haynes@garvan.org.au
Contact person for scientific queries
Name 75120 0
Ms Anne-Maree Haynes
Address 75120 0
Garvan Institute of Medical Research and The Kinghorn Cancer Centre, 370 Victoria St., Darlinghurst NSW 2010
Country 75120 0
Australia
Phone 75120 0
+61 2 9355 5786
Fax 75120 0
Email 75120 0
a.haynes@garvan.org.au

No information has been provided regarding IPD availability
Summary results
No Results