Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619001669189
Ethics application status
Approved
Date submitted
19/11/2019
Date registered
28/11/2019
Date last updated
28/04/2024
Date data sharing statement initially provided
28/11/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Clinical registry of focal low dose rate brachytherapy in men
with biopsy confirmed low-intermediate risk prostate cancer
Scientific title
Clinical registry of focal low dose rate brachytherapy to assess disease free progression and quality of life in men with biopsy confirmed low-intermediate risk prostate cancer.
Secondary ID [1] 299858 0
Nil known
Universal Trial Number (UTN)
Trial acronym
LIBERATE Clinical Registry
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prostate cancer 315260 0
Condition category
Condition code
Cancer 313560 313560 0 0
Prostate

Intervention/exposure
Study type
Observational
Patient registry
True
Target follow-up duration
60
Target follow-up type
Months
Description of intervention(s) / exposure
Enrolled participants will undergo a pre-plan volume study for the purpose of brachytherapy planning, followed by seed implantation 4-12 weeks later. Post-implantation, a non-contrast CT scan and/or MRI of the true pelvis will be acquired for the purpose of assessing implant quality and determining dose to organs at risk.

mp-MRI (T1/2, DWI, DCE) or PSMA PET - Pre-treatment and again at 18 to 36 months at the discretion f the treating physician.
TPM biopsy - Pre-treatment and again at 18 to 36 months at the discretion of the treating physician.
Assess eligibility criteria - pre-treatment
Review medical history - pre-treatment
Review medications - pre-treatment
Clinical assessment - pre-treatment and every visit up to 5 years
Informed consent - pre-treatment
PSA Assessment - pre-treatment and every visit up to 5 years
Focal LDR brachytherapy
Next day post-implant CT/MRI* - one day after LDR
Post-implant dosimetry - one day after LDR
Acute toxicities (CTCAE) - pre-treatment and again 6 weeks, and 3 months after treatment
Late toxicities (CTCAE) - 6,9, 12, 15, 18, 21 and 24 months after treatment then every 6 months up to 5 years
Questionnaires - pre-treatment, 6 weeks, 6 months, 12, 18, and 24 months then every 6 months up to 5 years.

Enrolment is projected to be completed in 60 months after opening. The follow-up period will be completed at up to 60 months after the last participant has been enrolled.

If patient meets progression, the following will be completed;
mp-MRI (T1/2, DWI, DCE) or PSMA PET
TPM biopsy
Clinical assessment
PSA Assessment
Intervention code [1] 316114 0
Not applicable
Comparator / control treatment
nil
Control group
Uncontrolled

Outcomes
Primary outcome [1] 322016 0
Local disease control - defined as the percentage of participants who report negative or clinically insignificant disease following repeat mp-MRI and Template Prostate Mapping (TPM) biopsy.
Timepoint [1] 322016 0
This endpoint will be assessed at 18 to 36 months after LDR brachytherapy seed implantation, or upon biochemical progression, whichever is earlier. Multi-parametric MRI fusion template prostate mapping (TPM) biopsy at this timepoint is standard following focal LDR brachytherapy for PCa.
Primary outcome [2] 322017 0
Biochemical progression free survival at 5 years - defined as an increase in PSA greater than or equal to 2ng/mL above the nadir in which the PSA velocity following the nadir was greater than 0.75ng/mL per year.
Timepoint [2] 322017 0
6 weeks post focal LDR brachytherapy , then at three-monthly intervals to 24 months then at six-monthly intervals to 5 years or upon withdrawal or pathological or biochemical failure.
Secondary outcome [1] 377018 0
Treatment related toxicity (assessed using Common Terminology Criteria for Adverse Events (CTCAE) V5.0).
Timepoint [1] 377018 0
6 weeks post focal LDR brachytherapy then at three-monthly intervals to 24 months, then at six-monthly intervals to 5 years.
Secondary outcome [2] 377019 0
Patient-reported Quality of Life as measured by the FACT-G7.
Timepoint [2] 377019 0
6 weeks post focal LDR brachytherapy then at six-monthly intervals to 5 years.
Secondary outcome [3] 377022 0
Biochemical progression free survival at 3 years - defined as an increase in PSA greater than or equal to 2ng/mL above the nadir in which the PSA velocity following the nadir was greater than 0.75ng/mL per year.
Timepoint [3] 377022 0
6 weeks post focal LDR brachytherapy , then at three-monthly intervals to 24 months then at six-monthly intervals to 3 years or upon withdrawal or pathological or biochemical failure.
Secondary outcome [4] 405807 0
Patient-reported Quality of Life as measured by the IPSS.
Timepoint [4] 405807 0
6 weeks post focal LDR brachytherapy then at six-monthly intervals to 5 years.
Secondary outcome [5] 405808 0
Patient-reported Quality of Life as measured by the IIEF.
Timepoint [5] 405808 0
6 weeks post focal LDR brachytherapy then at six-monthly intervals to 5 years.
Secondary outcome [6] 405809 0
Patient-reported Quality of Life as measured by the EPIC bowel domain.
Timepoint [6] 405809 0
6 weeks post focal LDR brachytherapy then at six-monthly intervals to 5 years.

Eligibility
Key inclusion criteria
• Men 40-85 years of age (inclusive).
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• Life expectancy more than 10 years based on co-morbidity not related to prostate cancer.
• Prostate specific antigen (PSA) level less than or equal to 10 ng/ml.
• Prostate cancer clinical stage T1c or T2a.
• PIRADS score of 3-5 (inclusive) or suspicious prostate lesion of PSMA PET.
• Reproducible template biopsy of the prostate gland demonstrating:
- Histologically-proven index lesion Gleason 6 (greater than or equal to 10mm in greater
than or equal to 1 core) or 7 (3+4) or 7 (4+3) (longest core < 10mm) adenocarcinoma
coinciding with mp-MRI;
- Template biopsies of the remaining gland, with minimum 18 cores taken for <40cc
prostate and 24 cores for 40-60cc prostate; and
- Non sector positive prostate containing no cancer or clinically insignificant cancer
(cancer core length <10mm Gleason 3+3).
• No significant urinary obstructive symptoms.
• Able to participate in the stipulated follow-up (either telephone follow-up or on-site visits acceptable, but one follow-up annually should be in person).
• Patients or their legal representatives must have the ability to read, understand and provide written informed consent.
Minimum age
40 Years
Maximum age
85 Years
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
• Evidence or suspicion of extra-capsular extension on MRI.
• Prostate cancer with significant sarcomatoid, ductal, spindle cell or neuroendocrine small cell components.
• Any other active malignancy (untreated, progressive or recurrent), except for non-melanoma skin cancer.
• Any inactive malignancy diagnosed within 5 years of entry, except for non-melanoma skin cancer.
• Any anatomical abnormality or medical condition precluding brachytherapy planning or treatment, or follow-up imaging (i.e. unable to cease anti-coagulant therapy, contraindications to anaesthesia, imperforate anus, TURP defect, diffuse intra-prostatic calcification, unfavourable prostatic geometry etc.)
• Chronic or acute prostatitis, neurogenic bladder, urinary tract infection, sphincter abnormalities, or any other symptom that prevents normal micturition.
• Patients who have received, or are receiving, any form of localised or systemic treatment (including ADT) for prostate carcinoma (excluding 5a-reductase inhibitors).
• Patients who are unwilling or unable to adhere to study requirements, including treatment and required assessments.

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
Sample size calculations were based upon the expected precision of point estimates for proportion of patients exhibiting local control at 18-to 36-months and biochemical progression-free survival at 5 years. Based upon prior studies, the proportion of patients exhibiting these endpoints would be expected to be at least 0.80 in each case. Using a precision of no wider than 0.15 and allowing for 10% attrition, a sample size of 100 is required.

The first primary endpoint (proportion of patients exhibiting local control at 18 to 36 months) will be analysed using proportions and the second primary endpoint (biochemical progression-free survival at 5 years) will be assessed using a single group Kaplan-Meier survival curve. In regard to secondary endpoints, changes in variables such as FACT-G7 over time will be assessed using methods appropriate for analysis of longitudinal data, such as mixed models/hierarchical linear modelling or generalised estimating equation (GEE) models appropriate to the scale of data being measured and the sample size. Appropriate graphs of changes over time and simple pairwise comparision between baseline and 6 weeks, then every 6 months up to 5 years or withdrawal will also be presented, with maximum change being expected between baseline and 6 weeks following treatment. 95% confidence intervals will be presented throughout, and any tests of statistical significance will employ an alpha of 0.05, two-tailed.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
30/01/2020
Actual
2/12/2019
Date of last participant enrolment
Anticipated
2/12/2024
Actual
Date of last data collection
Anticipated
2/12/2029
Actual
Sample size
Target
100
Accrual to date
115
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 15244 0
Icon Cancer Centre Epworth Freemasons - East Melbourne
Recruitment hospital [2] 15245 0
Icon Cancer Centre Richmond - Richmond
Recruitment hospital [3] 21617 0
Icon Cancer Centre Mulgrave - Mulgrave
Recruitment hospital [4] 21618 0
Icon Cancer Centre Geelong - Waurn Ponds
Recruitment hospital [5] 22214 0
Icon Cancer Centre Holmesglen - Moorabbin
Recruitment postcode(s) [1] 28553 0
3002 - East Melbourne
Recruitment postcode(s) [2] 28554 0
3121 - Richmond
Recruitment postcode(s) [3] 36545 0
3170 - Mulgrave
Recruitment postcode(s) [4] 36546 0
3216 - Waurn Ponds
Recruitment postcode(s) [5] 37376 0
3189 - Moorabbin

Funding & Sponsors
Funding source category [1] 304315 0
Charities/Societies/Foundations
Name [1] 304315 0
Icon Cancer Foundation
Country [1] 304315 0
Australia
Funding source category [2] 311275 0
Charities/Societies/Foundations
Name [2] 311275 0
Epworth Medical Foundation
Country [2] 311275 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
Icon Cancer Foundation
Address
Level 1, 22 Cordelia St, South Brisbane QLD 4101
Country
Australia
Secondary sponsor category [1] 304563 0
None
Name [1] 304563 0
none
Address [1] 304563 0
none
Country [1] 304563 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304769 0
Bellberry
Ethics committee address [1] 304769 0
123 Glen Osmond Road Eastwood Adelaide
South Australia 5063
Ethics committee country [1] 304769 0
Australia
Date submitted for ethics approval [1] 304769 0
20/09/2019
Approval date [1] 304769 0
20/11/2019
Ethics approval number [1] 304769 0

Summary
Brief summary
This study aims to establish a clinical registry, encompassing patient data from men with prostate cancer undergoing focal LDR brachytherapy.

Who is it for?
You may be eligible for this study if you are man aged between 40 and 85, with a diagnosis of Prostate cancer, clinical stage T1c or T2a.

Study details
The study visits will be 6 weeks following treatment, then three-monthly for 24 months following treatment, then six-monthly until five years following treatment. At these visits, various clinical assessment and blood tests will be performed. In addition, the study will also involve collecting data from multi-parametric-MRI scans, biopsies and questionnaires relating to quality of life and functional outcomes, particularly in the domains of urinary, gastro-intestinal and sexual function.

It is hoped that the registry can establish an evidence base for the national uptake of focal LDR brachytherapy, in addition to provider greater insight into the global body of data regarding primary focal therapy for PCa.
Trial website
nil
Trial related presentations / publications
nil
Public notes

Contacts
Principal investigator
Name 98142 0
Dr Andrew See
Address 98142 0
Icon Cancer Centre, Level 4, 32 Erin Street Richmond VIC 3121
Country 98142 0
Australia
Phone 98142 0
+61 3 9936 8277
Fax 98142 0
Email 98142 0
[email protected]
Contact person for public queries
Name 98143 0
Dr Lloyd Smyth
Address 98143 0
Icon Cancer Centre, Level 1, 22 Cordelia street, South Brisbane, QLD, 4101
Country 98143 0
Australia
Phone 98143 0
+61 7 3737 4500
Fax 98143 0
Email 98143 0
[email protected]
Contact person for scientific queries
Name 98144 0
Dr Andrew See
Address 98144 0
Icon Cancer Centre, Level 4, 32 Erin Street Richmond VIC 3121
Country 98144 0
Australia
Phone 98144 0
+61 3 9936 8277
Fax 98144 0
Email 98144 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.