Trial registered on ANZCTR


Trial ID
ACTRN12611000781943
Ethics application status
Approved
Date submitted
11/05/2009
Date registered
26/07/2011
Type of registration
Retrospectively registered

Titles & IDs
Public title
Radiotherapy following radical prostatectomy - Adjuvant Versus Early Salvage
Scientific title
Trans Tasman Radiation Oncology Group (TROG) 08.03 - A Phase III Multi-Centre Randomised Trial Comparing biochemical failure following Adjuvant Radiotherapy (RT) versus Early Salvage RT in Patients With Positive Margins or Extraprostatic Disease Following Radical Prostatectomy.
Secondary ID [1] 861 0
ClinicalTrials.gov ID NCT00860652
Universal Trial Number (UTN)
Trial acronym
RAVES

Health condition
Health condition(s) or problem(s) studied:
Prostate Cancer 4751 0
Condition category
Condition code
Cancer 237088 237088 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Arm 1: Standard Arm - Adjuvant Radiotherapy. Radiation: Adjuvant radiation therapy (ART) commenced within 4 months of Radical Prostatectomy (RP). 64Gy in 32 fractions to the prostate bed, radiotherapy will be delivered 1 fraction/day over approx 6.5 weeks.
Intervention code [1] 4525 0
Treatment: Other
Comparator / control treatment
Arm 2: Experimental - Active Surveillance with early salvage radiotherapy. Radiation: Early Salvage Radiotherapy. Active surveillance with early salvage RT (SRT). 64Gy in 32 fractions to the prostate bed, radiotherapy will be delivered 1 fraction/day over approx 6.5 weeks. The trigger for SRT is PSA (Prostate Speicific Antigen) level >= 0.2ng/ml. RT should commence as soon as possible )no later than 4 months) following the first PSA measurement >= 0.2ng/ml.
Control group
Active

Outcomes
Primary outcome [1] 5921 0
Biochemical failure: PSA >=0.4ng/ml and rising following RT. PSA will be measured through blood tests.
Timepoint [1] 5921 0
After 160 events have been observed, expected to be 5 years after the end of accrual.
Arm 1, Adjuvant Radiotherapy - 6 weeks post RT, then 6 monthly until the end of trial
Arm 2, Surveillance - every three months from randomisation for the first 5 years, then 6 monthly thereafter until rising PSA
Secondary outcome [1] 241999 0
Quality of Life. European Organisation for Research and Treatment of Cancer (EORTC) core quality of Life questionnaire (QLQ-C30) and EORTC (prostate Cancer module) QLQ-PR25 questionnaires
Timepoint [1] 241999 0
Pre-randomisation, Day 1 Radiotherapy (RT), last day RT and 6 weeks following completion of RT, then annually for 5 years.
Secondary outcome [2] 242000 0
Toxicity. Measured using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Effects (CTCAE) v 3.0
Timepoint [2] 242000 0
Final analysis will be after 160 events, estimated to be 5 years after the end of accrual.
Secondary outcome [3] 242001 0
Anxiety/Depression. Measured using the Hospital Anxiety and Depression Scale (HADS).
Timepoint [3] 242001 0
Pre-randomisation, Day 1 Radiotherapy (RT), last day RT and 6 weeks following completion of RT, then annually for 5 years.
Secondary outcome [4] 242002 0
Biochemical Failure free survival. Measured from date of randomisation to date of biochemical failure or death from any cause. Measured via Blood PSA tests.
Timepoint [4] 242002 0
Final analysis will be after 160 events, estimated to be 5 years after the end of accrual.
Arm 1, Adjuvant Radiotherapy - 6 weeks post RT, then 6 monthly until the end of trial
Arm 2, Surveillance - every three months from randomisation for the first 5 years, then 6 monthly thereafter until rising PSA
Secondary outcome [5] 242003 0
Overall Survival. Measured from date of randomisation to date of death from any cause. Local sites are responsible for reporting patient survival status. A patient will not be reported to have died unless there is source data confirming the patient?s death. Examples of potential source data are the patient?s medical records, obituaries, public records, death certificate, or information provided by a GP, hospice staff, or patient family members. If a patient is lost to follow-up, death will not be assumed unless confirmatory source data is available. The trial forms have been designed to allow sites to report lost to follow-up and death as separate events.
Timepoint [5] 242003 0
Final analysis will be after 160 events, estimated to be 5 years after the end of accrual. Clinical assessment - Every 6 months from randomisation for the first 5 years, then annually until the end of the trial.
PSA - Arm 1, Adjuvant Radiotherapy - 6 weeks post RT, then 6 monthly until the end of trial
Arm 2, Surveillance - every three months from randomisation for the first 5 years, then 6 monthly thereafter until rising PSA
Secondary outcome [6] 242004 0
Diseaese specific survival. Measured from the date of randomisation to date of death due to prostate cancer. Data linkage to medical records
Timepoint [6] 242004 0
Final analysis will be after 160 events, estimated to be 5 years after the end of accrual.
Secondary outcome [7] 242005 0
Time to distant failure. Measured from date of randomisation to date of documented regional, nodal or distant failure. Nodal failure - diagnosed by Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) of pelvis/abdomen.
Bone Metastases - confirmed on x-ray, bone scan, CT/MRI.
Timepoint [7] 242005 0
Baseline, 6 monthly from randomisation for first 5 years, then annually until the end of trial.
Secondary outcome [8] 242006 0
Time to local failure. Measured from date of randomisation to date of documented palpable or biopsy-proven local failure.
Timepoint [8] 242006 0
Final analysis will be after 160 events, estimated to be 5 years after the end of accrual. Baseline, 6 monthly from randomisation for first 5 years, then annually until the end of trial.
Secondary outcome [9] 242007 0
Time to initiation of androgen ablation. Measured from date of randomisation to the date of initiaion of androgen deprivation.
Timepoint [9] 242007 0
Final analysis will be after 160 events, estimated to be 5 years after the end of accrual. Baseline, 6 monthly from randomisation for first 5 years, then annually until the end of trial.
Secondary outcome [10] 242008 0
Quality Adjusted Life Years. Assessing efficacy and Quality of Life.
Timepoint [10] 242008 0
Final analysis will be after 160 events, estimated to be 5 years after the end of accrual.

Eligibility
Key inclusion criteria
1. Prior radical prostatectomy (RP) for adenocarcinoma of the prostate. 2. Histological confirmation of adenocarcinoma of the prostate with Gleason score reported (RP specimen). 3. Patients must have at least one of the following risk factors: a) positive margins, b) extraprostatic extension (EPE) with or without seminal vesicle involvement (pT3a or pT3b). 4. Capable of starting RT within 4 months of RP (a requirement if randomised to adjuvant RT arm). 5. Most recent PSA <= 0.1ng/ml following RP and prior to randomisation. 6. European Cooperative Oncology Group (ECOG) performance status 0-1. 7. Patient able to adhere to the specified follow-up schedule and complete the Quality Of Life and anxiety/depression self assessments. 8. Written informed consent obtained prior to randomisation. 9. Completion of all pre-treatment evaluations. 10. 18 years or older.
Minimum age
18 Years
Maximum age
No limit
Gender
Males
Can healthy volunteers participate?
No
Key exclusion criteria
1. Previous pelvic RT. 2. Concurrent or previous malignancy 5 years prior to randomisation (except non-melanomatous skin cancer). 3. Androgen deprivation (AD) prior to or following RP. 4. Evidence of nodal or distant metastases. 5. Co-morbidities that would interfere with the completion of treatment or 5 years of follow-up. 6. Concurrent cytotoxic medication. 7. Hip prothesis

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Patients will be registered via the internet. The Trial Centre will provide each participating site with a user account to access the web-based system. To register a patient, complete electronic case report forms (CRFs) to document eligibility and stratification fators. Prior to patient registration, the investigator should ensure that
all of the following requirements are met:
- Informed consent has been obtained prior to performing any study specific procedures
- The patient meets all inclusion criteria and none of the exclusion criteria should apply.
- All pre-registration assessments and investigations have been performed.
- The eligibility checklist has been completed, signed and dated.

Once registered, patients will be randomised to one of two treatment arms via a web based randomisation using the minisation technique.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Stratification: Pre-operative PSA; Gleason score; Margin positivity; Seminal vesicle involvement; Radiotherapy Institution.
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Efficacy

Recruitment
Anticipated date of first participant enrolment
30/03/2009
Actual date of first participant enrolment
30/03/2009
Anticipated date last participant enrolled
31/12/2016
Actual date last participant enrolled
31/12/2015
Target sample size
470
Actual sample size
333
Recruitment status
Closed: follow-up continuing
Recruitment in Australia
Recruitment state(s)
NSW,VIC,QLD,WA,TAS
Recruitment hospital [1] 576 0
The Alfred - Prahran
Recruitment hospital [2] 577 0
Austin Health - Heidelberg Repatriation Hospital - Heidelberg West
Recruitment hospital [3] 578 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [4] 579 0
Campbelltown Hospital - Campbelltown
Recruitment hospital [5] 581 0
Liverpool Hospital - Liverpool
Recruitment hospital [6] 582 0
Nepean Hospital - Kingswood
Recruitment hospital [7] 583 0
Peter MacCallum Cancer Institute - East Melbourne
Recruitment hospital [8] 584 0
Port Macquarie Base Hospital - Port Macquarie
Recruitment hospital [9] 585 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [10] 586 0
Riverina Cancer Care Centre - Wagga Wagga
Recruitment hospital [11] 587 0
Royal Brisbane & Womens Hospital - Herston
Recruitment hospital [12] 589 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [13] 590 0
Royal Perth Hospital - Perth
Recruitment hospital [14] 591 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [15] 592 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [16] 593 0
St George Hospital - Kogarah
Recruitment hospital [17] 594 0
The Townsville Hospital - Douglas
Recruitment hospital [18] 595 0
Sydney Adventist Hospital - Wahroonga
Recruitment hospital [19] 2784 0
Bloomfield Hospital - Orange
Recruitment hospital [20] 3485 0
Westmead Hospital - Westmead
Recruitment hospital [21] 3487 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment hospital [22] 3488 0
Mater Private Hospital - South Brisbane
Recruitment hospital [23] 3489 0
St Andrew's Toowoomba Hospital - Toowoomba
Recruitment hospital [24] 3490 0
Nambour General Hospital - Nambour
Recruitment hospital [25] 3491 0
Gold Coast Hospital - Southport
Recruitment hospital [26] 4221 0
Genesis Cancer Care QLD - Southport
Recruitment hospital [27] 4222 0
St John of God Hospital, Subiaco - Subiaco
Recruitment hospital [28] 4223 0
Fiona Stanley Hospital - Murdoch
Recruitment postcode(s) [1] 6322 0
3181 - Prahran
Recruitment postcode(s) [2] 6323 0
3081 - Heidelberg West
Recruitment postcode(s) [3] 6324 0
2310 - Hunter Region
Recruitment postcode(s) [4] 6325 0
2170 - Liverpool
Recruitment postcode(s) [5] 6326 0
2450 - Coffs Harbour
Recruitment postcode(s) [6] 6327 0
2747 - Kingswood
Recruitment postcode(s) [7] 6328 0
6014 - Wembley
Recruitment postcode(s) [8] 6329 0
8006 - Abeckett Street
Recruitment postcode(s) [9] 6330 0
2444 - Port Macquarie
Recruitment postcode(s) [10] 6332 0
4102 - Woolloongabba
Recruitment postcode(s) [11] 6333 0
4101 - South Brisbane
Recruitment postcode(s) [12] 6334 0
2650 - Wagga Wagga
Recruitment postcode(s) [13] 6336 0
2065 - Royal North Shore Hospital
Recruitment postcode(s) [14] 6337 0
6000 - Perth
Recruitment postcode(s) [15] 6338 0
2050 - Camperdown
Recruitment postcode(s) [16] 6339 0
2217 - Kogarah
Recruitment postcode(s) [17] 6340 0
2010 - Darlinghurst
Recruitment postcode(s) [18] 6342 0
2076 - Wahroonga
Recruitment postcode(s) [19] 9253 0
2145 - Westmead
Recruitment postcode(s) [20] 9256 0
4101 - Highgate Hill
Recruitment postcode(s) [21] 9257 0
4350 - Toowoomba
Recruitment postcode(s) [22] 9258 0
4560 - Nambour
Recruitment postcode(s) [23] 9259 0
4215 - Southport
Recruitment postcode(s) [24] 10188 0
6150 - Murdoch
Recruitment postcode(s) [25] 10189 0
4006 - Herston
Recruitment postcode(s) [26] 10190 0
2560 - Campbelltown
Recruitment postcode(s) [27] 10191 0
2065 - St Leonards
Recruitment postcode(s) [28] 10192 0
6009 - Nedlands
Recruitment postcode(s) [29] 10193 0
4354 - Douglas
Recruitment postcode(s) [30] 10194 0
2800 - Orange
Recruitment postcode(s) [31] 10195 0
4217 - Gold Coast
Recruitment outside Australia
Country [1] 1758 0
New Zealand
State/province [1] 1758 0
Palmerston North
Country [2] 4862 0
New Zealand
State/province [2] 4862 0
Dunedin
Country [3] 4864 0
New Zealand
State/province [3] 4864 0
Wellington
Country [4] 4865 0
New Zealand
State/province [4] 4865 0
Auckland
Country [5] 4866 0
New Zealand
State/province [5] 4866 0
Christchurch
Country [6] 7108 0
New Zealand
State/province [6] 7108 0
Tauranga

Funding & Sponsors
Funding source category [1] 4932 0
Government body
Name [1] 4932 0
Australian National Health and Research Council
Address [1] 4932 0
Level 5 20 Allara St Canberra ACT 2601
Country [1] 4932 0
Australia
Funding source category [2] 4933 0
Other
Name [2] 4933 0
Royal Australian and New Zealand College of Radiologists
Address [2] 4933 0
Level 9 Druitt St Sydney NSW 2000 Australia
Country [2] 4933 0
Australia
Funding source category [3] 4934 0
Hospital
Name [3] 4934 0
Auckland City Hospital
Address [3] 4934 0
Auckland City Hospital
2 Park Road Grafton
Auckland 1023
Country [3] 4934 0
New Zealand
Funding source category [4] 4935 0
Government body
Name [4] 4935 0
Cancer Council Victoria
Address [4] 4935 0
1 Rathdowne St Carlton VIC, 3053 Australia
Country [4] 4935 0
Australia
Funding source category [5] 4936 0
Government body
Name [5] 4936 0
Cancer Council NSW
Address [5] 4936 0
153 Dowling St Woolloomooloo, NSW 2011 Australia
Country [5] 4936 0
Australia
Funding source category [6] 4937 0
Government body
Name [6] 4937 0
New Zealand Health and Research Council
Address [6] 4937 0
Level 3 110 Stanley St Auckland 1010 New Zealand
Country [6] 4937 0
New Zealand
Funding source category [7] 4939 0
Other
Name [7] 4939 0
Trans Tasman Radiation Oncology Group
Address [7] 4939 0
TROG Central Operations Office
Calvary Mater Newcastle
Locked Bag 7 HRMC
NSW 2310 Australia
Country [7] 4939 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Trans Tasman Radiation Oncology Group (TROG)
Address
TROG Central Operations Office Calvary Mater Newcastle Locked Bag 7 HRMC NSW 2310 Australia
Country
Australia
Secondary sponsor category [1] 4460 0
None
Name [1] 4460 0
Address [1] 4460 0
Country [1] 4460 0
Other collaborator category [1] 667 0
Other
Name [1] 667 0
Urological Society of Australia and New Zealand
Address [1] 667 0
Suite 512 East point
180 Ocean Street Edgecliff, NSW 2027 Australia
Country [1] 667 0
Australia
Other collaborator category [2] 277280 0
Other Collaborative groups
Name [2] 277280 0
Australian & New Zealand Urogenital and Prostate Cancer Trials Group
Address [2] 277280 0
Level 4, 92-94 Parramatta Road, Camperdown NSW 2050
Country [2] 277280 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 7015 0
Royal North Shore Hospital
Ethics committee address [1] 7015 0
Level 2 Building 51
Royal North Shore Hospital
St Leonards, NSW 2065
Ethics committee country [1] 7015 0
Australia
Date submitted for ethics approval [1] 7015 0
Approval date [1] 7015 0
30/10/2008
Ethics approval number [1] 7015 0
08/HAWK/131

Summary
Brief summary
This study aims to compare two different radiotherapy regimes following radical prostatectomy in men with prostate cancer. Who is it for? You may be eligible to join this study if you a male aged 18 years or above who has undergone a radical prostatectomy (RP) for prostate cancer, and are able to start radiotherapy within 4 months of RP. Study details Participants in this study will be randomly (by chance) allocated to one of two groups. Participants in one group will receive the current standard of care treatment, which consists of adjuvant radiation therapy (ART) commenced within 4 months of radical prostatectomy. Participants in the other group will instead undergo active surveillance, where salvage radiotherapy (SRT) will not commence until Prostate Specific Antigen (PSA) reaches a level greater than 0.2ng/ml. Both radiotherapy regimes will be delivered once per day over approximately 6.5 weeks. Quality of life self-assessment questionnaires, Hospital Anxiety and Depression Score and toxicity will be assessed at baseline, the end of radiotherapy and annually for 5 years. Patients will be seen by their doctor 6 monthly for the first 5 years, then annually for the next 5 years. A blood test measuring PSA is done 3 monthly for the first 5 years for patients randomised to early SRT, than 6 monthly from years 5-10.
Trial website
www.trog.com.au
Trial related presentations / publications
Trada Y, Kneebone A, Paneghel A, Pearse M, Sidhom M, Tang C,
Wiltshire K, Haworth A, Fraser-Browne C, Martin J. Optimising
Radiation therapy Quality Assurance in Clinical Trials: A TROG 08.03
RAVES sub-study. International Journal of Radiation Oncology Biology and Physics. 2015; 93:1045-1051
Public notes

Contacts
Principal investigator
Name 29589 0
A/Prof A/Prof Andrew Kneebone and Dr Maria Pearse (Co PIs)
Address 29589 0
Department of Radiation Oncology Royal North Shore Hospital Pacific Highway St Leonards NSW 2065 Australia

and

Oncology Department Auckland Regional Cancer and Blood Service Private Bag 92024 Auckland, New Zealand 1142
Country 29589 0
Australia
Phone 29589 0
+61 2 9926 5010 / +64095074949
Fax 29589 0
Email 29589 0
AKneebone@nsccahs.health.nsw.gov.au & mariap@adhb.govt.nz
Contact person for public queries
Name 12836 0
Ms Carol Fraser-Browne
Address 12836 0
Clinical Trial Centre Manager
Oncology Department
Auckland Regional Cancer and Blood Service
Private Bag 92024
Auckland, New Zealand 1142
Country 12836 0
New Zealand
Phone 12836 0
+64 9 307 4949 ext 23044
Fax 12836 0
+64 9 359 9981
Email 12836 0
CarolFB@adhb.govt.nz
Contact person for scientific queries
Name 3764 0
A/Prof Andrew Kneebone
Address 3764 0
Department of Radiation Oncology
Royal North Shore Hospital
Pacific Highway St Leonards NSW 2065 Australia
Country 3764 0
Australia
Phone 3764 0
+61 2 9926 5010
Fax 3764 0
+61 2 9906 4150
Email 3764 0
AKneebone@nsccahs.health.nsw.gov.au