Radiotherapy - Adjuvant Versus Early Salvage (RAVES)

• ClinicalTrials.gov Identifier: NCT00860652
• Recruitment Status: Active, not recruiting
• First Posted: March 12, 2009
• Last Update Posted: November 18, 2022
• Sponsor: Trans Tasman Radiation Oncology Group
• Collaborators: Urological Society of Australia and New Zealand (USANZ); Australian and New Zealand Urogenital and Prostate Cancer Trials Group
• Information provided by (Responsible Party): Trans Tasman Radiation Oncology Group

Study Description

Brief Summary:

Radical prostatectomy (RP) is the most common curative approach offered to men with newly diagnosed prostate cancer. Unfortunately, up to half of these patients will have factors placing them at high risk of their cancer recurring. Having radiotherapy after RP is known to improve cure rates, but what is not known is whether it should be given straight after the operation or only when there is a rising PSA after surgery indicating active cancer. Immediate RT may not benefit all men, and can cause serious side effects such as bladder and bowel problems and impotence. International lack of consensus on the optimal timing of RT has resulted in varied clinical practice. This phase 3 trial will compare the two approaches.

Condition or disease	Intervention/treatment	Phase
Prostate Cancer	Radiation: Adjuvant Radiotherapy; Radiation: Early Salvage Radiotherapy	Not Applicable

Detailed Description:

This is a prospective, multi-centre, international, randomised controlled trial with a 1:1 allocation ratio. Patients with positive margins and/or pT3 disease will be randomised to adjuvant RT (Standard Arm) or active surveillance with salvage RT delivered at early relapse (Experimental Arm). 64 Gy in 32 fractions will be delivered to the prostate bed. QoL self-assessment questionnaires, Hospital Anxiety and Depression Score and toxicity will be assessed at baseline, the end of RT 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 prostate specific antigen (PSA) is done 3 monthly for the first 5 years for patients randomised to early salvage RT, then 6 monthly from years 5 to 10.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 333 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Radiotherapy - Adjuvant Versus Early Salvage. A Phase III Multi-centre Randomised Trial Comparing Adjuvant Radiotherapy (RT) With Early Salvage RT in Patients With Positive Margins or Extraprostatic Disease Following Radical Prostatectomy.
• Actual Study Start Date: March 3, 2009
• Estimated Primary Completion Date: December 2022
• Estimated Study Completion Date: December 2026

Arms and Interventions

Arm	Intervention/treatment
Experimental: Adjuvant Radiotherapy (RT); Adjuvant Radiotherapy (64Gy in 32 Fractions to the prostate bed)	Radiation: Adjuvant Radiotherapy; Adjuvant RT (ART) commenced within 4 months of Radical Prostatectomy. 64Gy in 32 fractions to the prostate bed.; Other Name: ART, Radiation
Experimental: Active Surveillance with Early SalvageRT; Active Surveillance with Early Salvage Radiotherapy	Radiation: Early Salvage Radiotherapy; Active surveillance with early Salvage RT (SRT). SRT - 64Gy in 32 fractions to the prostate bed. RT should commence no later than 4 months following the first PSA measurement ≥ 0.2ng/mL.; Other Name: SRT, Surveillance, Radiation

Outcome Measures

Primary Outcome Measures :

1. Biochemical failure: PSA ≥ 0.4 ng/ml and rising following RT [ Time Frame: After 160 events have been observed, expected to be 5 years after recruitment closes ]

Secondary Outcome Measures :

1. Quality of Life [ Time Frame: Final Analysis will be after 160 events, estimated to be five years after the end of accrual ]
2. Toxicity [ Time Frame: Final analysis will be after 160 events, estimated to be 5 years after end of accrual. ]
3. Anxiety/Depression [ Time Frame: Final analysis will be after 160 events, estimated to be 5 years after end of accrual. ]
4. Biochemical failure-free survival [ Time Frame: Final analysis will be after 160 events, estimated to be 5 years after end of accrual. ]
5. Overall survival [ Time Frame: Final analysis will be after 160 events, estimated to be 5 years after end of accrual. ]
6. Disease-specific survival [ Time Frame: Final analysis will be after 160 events, estimated to be 5 years after end of accrual. ]
7. Time to distant failure [ Time Frame: Final analysis will be after 160 events, estimated to be 5 years after end of accrual. ]
8. Time to local failure [ Time Frame: Final analysis will be after 160 events, estimated to be 5 years after end of accrual. ]
9. Time to the initiation of androgen ablation [ Time Frame: Final analysis will be after 160 events, estimated to be 5 years after end of accrual. ]
10. Quality adjusted life years [ Time Frame: Final analysis will be after 160 events, estimated to be 5 years after end of accrual. ]
11. Cost-utility [ Time Frame: Final analysis will be after 160 events, estimated to be 5 years after end of accrual. ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Prior Radical Prostatectomy (RP) for adenocarcinoma of the prostate.
• Histological confirmation of adenocarcinoma of the prostate with the Gleason score reported (Radical Prostatectomy specimen).
• Patients must have at least one of the following risk factors: 1) Positive margins, 2) Extraprostatic extension (EPE) with or without seminal vesicle involvement (pT3a or pT3b)
• Capable of starting RT within 4 months of RP (a requirement if randomised to adjuvant RT arm)
• Most recent PSA ≤ 0.10 ng/ml following RP and prior to randomisation
• Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1
• Patient able to adhere to the specified follow-up schedule and complete the Quality of Life and anxiety/depression self-assessments
• Written informed consent obtained prior to randomisation
• Completion of all pre-treatment evaluations
• 18 years and older

Exclusion Criteria:

• Previous pelvic RT
• Androgen deprivation (AD) prior to or following RP
• Evidence of nodal or distant metastases
• Co-morbidities that would interfere with the completion of treatment and/or 5 years of follow-up
• Concurrent cytotoxic medication
• Hip prosthesis

Contacts and Locations

Locations

Australia, New South Wales

Campbelltown Hopsital

Campbelltown, New South Wales, Australia, 2170

Royal Prince Alfred Hospital

Camperdown, New South Wales, Australia, 2050

Coffs Harbour Health Campus, NCCI

Coffs Harbour, New South Wales, Australia, 2450

Radiation Oncology Associates

Darlinghurst, New South Wales, Australia, 2010

St Vincent's Clinic

Darlinghurst, New South Wales, Australia

Nepean Hospital

Kingswood, New South Wales, Australia, 2747

St George Hospital

Kogarah, New South Wales, Australia, 2217

Liverpool Hospital

Liverpool, New South Wales, Australia, 1871

Calvary Mater Newcastle

Newcastle, New South Wales, Australia, 2310

Central West Cancer Services (Orange Health)

Orange, New South Wales, Australia

Port Macquarie Base Hospital, NCCI

Port Macquarie, New South Wales, Australia, 2444

Royal North Shore Hospital

St Leonards, New South Wales, Australia, 2065

Riverina Cancer Care Centre

Wagga Wagga, New South Wales, Australia, 2650

Sydney Adventist Hospital

Wahroonga, New South Wales, Australia, 2076

Westmead Hospital

Westmead, New South Wales, Australia, 2145

Australia, Queensland

Radiation Oncology Gold Coast

Gold Coast, Queensland, Australia, 4217

Royal Brisbane and Women's Hospital

Herston, Queensland, Australia, 4029

Oceania Oncology

Nambour, Queensland, Australia, 4560

Radiation Oncology - Mater Centre

South Brisbane, Queensland, Australia, 4101

Toowoomba Cancer Research Centre

Toowoomba, Queensland, Australia, 4350

Townsville Hospital

Townsville, Queensland, Australia, 4814

Premion

Tugun, Queensland, Australia, 4224

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia, 4102

Australia, Victoria

Peter MacCallum Cancer Centre

East Melbourne, Victoria, Australia, 3002

Austin Hospital

Heidelberg West, Victoria, Australia, 3081

The Alfred/WBRC

Melbourne, Victoria, Australia, 3004

Australia, Western Australia

Fiona Stanley Hospital

Murdoch, Western Australia, Australia, 6150

Sir Charles Gairdner Hospital

Nedlands, Western Australia, Australia, 6009

Royal Perth Hospital

Perth, Western Australia, Australia, 6000

Perth Radiation Oncology

Perth, Western Australia, Australia, 6014

New Zealand

Auckland Radiation Oncology

Epsom, Auckland, New Zealand, 1023

Wellington Hospital

Newtown, Wellington, New Zealand, 6021

Auckland Hospital

Auckland, New Zealand

Christchurch Hospital

Christchurch, New Zealand

Dunedin Hospital

Dunedin, New Zealand, 9016

Palmerston North Hospital

Palmerston North, New Zealand, 4414

Sponsors and Collaborators

Trans Tasman Radiation Oncology Group

Urological Society of Australia and New Zealand (USANZ)

Australian and New Zealand Urogenital and Prostate Cancer Trials Group

Investigators

• Study Chair: Maria Pearse, MBChB; Trans Tasman Radiation Oncology Group
• Study Chair: Andrew Kneebone; Trans Tasman Radiation Oncology Group

More Information

Additional Information:

Trans Tasman Radiation Oncology Group 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Kneebone A, Fraser-Browne C, Duchesne GM, Fisher R, Frydenberg M, Herschtal A, Williams SG, Brown C, Delprado W, Haworth A, Joseph DJ, Martin JM, Matthews JHL, Millar JL, Sidhom M, Spry N, Tang CI, Turner S, Wiltshire KL, Woo HH, Davis ID, Lim TS, Pearse M. Adjuvant radiotherapy versus early salvage radiotherapy following radical prostatectomy (TROG 08.03/ANZUP RAVES): a randomised, controlled, phase 3, non-inferiority trial. Lancet Oncol. 2020 Oct;21(10):1331-1340. doi: 10.1016/S1470-2045(20)30456-3.

• Responsible Party: Trans Tasman Radiation Oncology Group
• ClinicalTrials.gov Identifier: NCT00860652
• Other Study ID Numbers: TROG 08.03
• First Posted: March 12, 2009
• Last Update Posted: November 18, 2022
• Last Verified: November 2022

Keywords provided by Trans Tasman Radiation Oncology Group:

Oncology; Prostate Cancer; Radiotherapy; Radical Prostatectomy; Prior Radical Prostatectomy (RP); Histological Confirmation of adenocarcinoma of the prostate; Positive margins and/or extraprostatic extension (EPE)

Additional relevant MeSH terms:

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases