Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622001478707
Ethics application status
Approved
Date submitted
7/11/2022
Date registered
24/11/2022
Date last updated
24/11/2022
Date data sharing statement initially provided
24/11/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Evaluating the efficacy of radiation therapy compared to surveillance in men with prostate cancer that has returned after surgery and negative Prostate specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) scan.
Scientific title
A multi-centre, randomised phase 2 clinical trial of early salvage radiotherapy versus surveillance on the incidence of biochemical recurrence after radical prostatectomy for men with prostate cancer, incorporating clinical and imaging-based risk stratification.
Secondary ID [1] 308298 0
Nil known
Universal Trial Number (UTN)
Trial acronym
DIPPER (Dedicated Imaging Post-Prostatectomy for Enhanced Radiotherapy outcomes)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prostate cancer 328084 0
Condition category
Condition code
Cancer 325141 325141 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Salvage radiotherapy (SRT)
Participants allocated to SRT group will receive a course of radiotherapy to the area where the prostate gland used to be (the prostate bed) and potentially to the lymph glands related to the prostate in the pelvis. Salvage radiotherapy should commence within eight weeks of enrolment. Radiotherapy plan will occur according to Participants treating radiation oncologist. Before starting the radiotherapy, participant will have a CT scan of the pelvic area, which is used to plan the radiotherapy. Pelvic lymph node radiotherapy (PLNRT) treatment is optional, according to clinician discretion. The radiotherapy is given over about 6 and half weeks. Participants will need to come in for treatment 5 times a week and will have a total of 32-35 treatments. Each radiotherapy treatment will take approximately 15 minutes each day. Following the radiotherapy, review appointments and investigations will be carried out including prostate-specific antigen (PSA) blood testing per usual standard of care. These assessments are scheduled every 6 months post-randomisation for a minimum of 3 years post-randomisation or until study end. Participants will also be asked to complete a series of questionnaires to provide information on their health and wellbeing at baseline, 6 months post-randomisation, then annually for a minimum of 3 years post-randomisation or until study end.
Intervention code [1] 324751 0
Prevention
Comparator / control treatment
Surveillance without radiotherapy
Participants will undergo clinic assessment and PSA blood test per usual standard of care at baseline, 6 months post-randomisation, then 6 monthly for a minimum of 3 years post-randomisation or until study end. Participants will also be asked to complete a series of questionnaires to provide information on their health and wellbeing at baseline, 6 months post-randomisation, then annually for a minimum of 3 years post-randomisation or until study end. The overall duration of the surveillance is 3 years post-randomisation.
Control group
Active

Outcomes
Primary outcome [1] 332966 0
Event free survival
Timepoint [1] 332966 0
6 months post-randomisation, then 6 monthly for a minimum of 3 years post-randomisation or until study end.
Secondary outcome [1] 415361 0
Health-related quality of life assessed using the European Organisation for Research Treatment of Cancer (EORTC) quality of life questionnaire (QLQ-C30, version 3).
Timepoint [1] 415361 0
Baseline, 6 months post-randomisation, then annually for a minimum of 3 years post-randomisation or until study end.
Secondary outcome [2] 415362 0
To determine variation in treatment patterns
Use of Pelvic lymph node radiotherapy (PLNRT) in low-risk population will be recorded. In the event of cross-over, participants will be asked for motivations for this change in initial treatment approach. Cross-over participants are those in surveillance group who refuse surveillance and want salvage radiotherapy and vice-versa for salvage radiotherapy group.
Timepoint [2] 415362 0
6 months post-randomisation, then 6 monthly for a minimum of 3 years post-randomisation or until study end.
Secondary outcome [3] 415995 0
Prostate cancer-specific health-related quality of life assessed using the European Organisation for Research Treatment of Cancer (EORTC) quality of life questionnaire (QLQ-PR25)
Timepoint [3] 415995 0
Baseline, 6 months post-randomisation, then annually for a minimum of 3 years post-randomisation or until study end.
Secondary outcome [4] 415996 0
Fear of cancer recurrence (FCRI) assessed using FCRI Severity subscale (short form, FCRI-SF). FCRI-SF is an abbreviated version of the original 42-item instrument with strong correlation with the total FCRI score.
Timepoint [4] 415996 0
Baseline, 6 months post-randomisation, then annually for a minimum of 3 years post-randomisation or until study end.

Eligibility
Key inclusion criteria
1. Previous prostate cancer diagnosis treated with radical prostatectomy
2. Post-prostatectomy biochemical recurrence (Prostate-specific antigen (PSA) 0.2 - 0.5 nanograms per milliliter) with documented 2 consecutive PSA rises taken at least 14 days apart
3. Low risk features (Gleason score less than equal to 3 plus 4 / ISUP grade group less than equal to 2 and PSA doubling time greater than 12 months)
4. Willing to complete study requirements (treatments, questionnaires etc.)
5. ECOG performance status 0 or 1
6. Estimated life expectancy greater than 7yrs
7. Prior PSMA PET/CT for investigation of early biochemical recurrence
8. Prior pelvic radiation therapy that would impact delivery of the protocol radiotherapy
Minimum age
18 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
1. Contraindications to radiotherapy (e.g., active inflammatory bowel disease)
2. Prior or current androgen deprivation therapy (ADT) or other systemic therapy for prostate cancer
3. Bilateral orchidectomy
4. Positive regional nodal disease (N1 positive) at radical prostatectomy
5. Evidence of metastatic disease on any imaging modality
6. History of another malignancy within 5 years prior to randomisation except for those listed
7. Concurrent illness that might jeopardise the ability to undergo study procedures
8. Participation in other clinical trials of investigational agents for treatment of prostate cancer or other diseases

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e., computerised sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
134 men are required to undergo PSMA PET/CT to reach the 100 participants required. This calculation is based on a log-rank test of time to event with a 2-sided alpha of 5 percent and allows for 10 percent loss to follow-up over 3 years.
The primary analyses will consist of a Kaplan-Meier plot and a log-rank test comparing survival times between surveillance and radiation therapy arms. A secondary analysis will consider the primary analysis on a per-protocol basis (rather than intention-to-treat). Sensitivity analyses adjusting for important prognostic factors will be conducted using Cox regression. Secondary patient reported outcome measures will be analysed using hierarchical linear models with random site effects. The secondary treatment pattern outcome of use of Pelvic lymph node radiotherapy in low-risk population will be analysed using a log-binomial or logistic hierarchical model with a random effect at site level.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/02/2023
Actual
Date of last participant enrolment
Anticipated
3/02/2025
Actual
Date of last data collection
Anticipated
1/02/2028
Actual
Sample size
Target
100
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 23471 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [2] 23472 0
Royal Brisbane & Womens Hospital - Herston
Recruitment hospital [3] 23473 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [4] 23474 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment postcode(s) [1] 38879 0
3000 - Melbourne
Recruitment postcode(s) [2] 38880 0
4029 - Herston
Recruitment postcode(s) [3] 38881 0
2065 - St Leonards
Recruitment postcode(s) [4] 38882 0
2010 - Darlinghurst

Funding & Sponsors
Funding source category [1] 312548 0
Other Collaborative groups
Name [1] 312548 0
The Australian and New Zealand Urogenital and Prostate Cancer Trials Group Ltd
Country [1] 312548 0
Australia
Primary sponsor type
Other Collaborative groups
Name
The Australian and New Zealand Urogenital and Prostate Cancer Trials Group Ltd
Address
Lifehouse, Level 6, 119-143 Missenden Road, Camperdown, New South Wales 2050
Country
Australia
Secondary sponsor category [1] 314149 0
Commercial sector/Industry
Name [1] 314149 0
Mundipharma Pty Ltd.
Address [1] 314149 0
Level 24, 88 Phillip Street, Sydney New South Wales 2000
Country [1] 314149 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311875 0
St Vincent's Hospital Human Research Ethics Committee
Ethics committee address [1] 311875 0
St Vincent’s Hospital Translational Research Centre, 97-105 Boundary Street, Darlinghurst, New South Wales 2010
Ethics committee country [1] 311875 0
Australia
Date submitted for ethics approval [1] 311875 0
24/07/2022
Approval date [1] 311875 0
20/10/2022
Ethics approval number [1] 311875 0
2022/ETH01222

Summary
Brief summary
This study aims to compare radiation therapy delivered directly to the prostate with or without radiotherapy to close lymph glands, to active surveillance in terms of cancer control, in a carefully selected group of men with prostate cancer.

Who is it for?
You may be eligible for this study if you are an adult male aged 18 or older, who has previously been treated for prostate cancer, including removal of all or part of your prostate. In particular, people who still have active prostate cancer that has low risk features and negative Prostate specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) imaging will be eligible.

Study details
Participants who choose to enroll in this study will be randomly allocated by chance (similar to flipping a coin) to one of the two study groups. Participants who are allocated to the first group will not undergo radiotherapy and will be seen in clinic at regular intervals by their doctor for routine check-ups and blood tests. The PSA blood test will be done every 6 months to allow surveillance of their cancer. Participants who are allocated to the second group will undergo specific radiotherapy to their prostate area with or without radiotherapy of their pelvic lymph nodes as decided by the treating clinician. Before starting the radiotherapy, participants will have a CT scan of the area where the prostate gland used to be (the prostate bed) and potentially the lymph glands related to the prostate in the pelvis to plan the radiotherapy. The radiotherapy is given over about 6 and half weeks. Participants will need to come in for treatment 5 times a week and will have a total of 32-35 treatments. Each radiotherapy treatment will take approximately 15 minutes each day. Following the radiotherapy, review appointments and investigations will be carried out every 6 months including PSA blood testing.
All participants will be asked to complete a series of questionnaires to provide information on their health and wellbeing for up to 3 years after enrolment into the study. It is anticipated that completing these questionnaires will take about 20 minutes at each timepoint.
It is hoped this research will determine whether additional radiotherapy directly to the prostate area after removal of the prostate is effective in controlling cancer recurrence in these low-risk patients. If the radiotherapy treatment is found to be better at controlling cancer recurrence for prostate cancer patients compared to the standard care surveillance, it may be introduced as a standard of care for all prostate cancer patients.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 122682 0
A/Prof Matthew J. Roberts
Address 122682 0
Department of Urology, Royal Brisbane and Women's Hospital, Cnr Butterfield St and Bowen Bridge Rd, Herston, Queensland 4029
Country 122682 0
Australia
Phone 122682 0
+61422378975
Fax 122682 0
Email 122682 0
[email protected]
Contact person for public queries
Name 122683 0
Ms Margaret McJannett
Address 122683 0
ANZUP Cancer Trials Group Ltd, Level 6, 119-143 Missenden Rd, Camperdown, New South Wales 2050
Country 122683 0
Australia
Phone 122683 0
+61290543600
Fax 122683 0
Email 122683 0
[email protected]
Contact person for scientific queries
Name 122684 0
Ms Margaret McJannett
Address 122684 0
ANZUP Cancer Trials Group Ltd, Level 6, 119-143 Missenden Rd, Camperdown, New South Wales 2050
Country 122684 0
Australia
Phone 122684 0
+61290543600
Fax 122684 0
Email 122684 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
Medical data pertaining to an individual will not be made public. Only aggregate summary data will be published.


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
SourceTitleYear of PublicationDOI
EmbaseTreatment de-intensification for low-risk biochemical recurrence after radical prostatectomy: rational or risky?.2023https://dx.doi.org/10.1111/bju.16086
EmbaseThe Dedicated Imaging Post-Prostatectomy for Enhanced Radiotherapy outcomes (DIPPER) trial protocol: a multicentre, randomised trial of salvage radiotherapy versus surveillance for low-risk biochemical recurrence after radical prostatectomy.2023https://dx.doi.org/10.1111/bju.16158
N.B. These documents automatically identified may not have been verified by the study sponsor.