Radiotherapy - Adjuvant Versus Early Salvage (RAVES)

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.

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Prostate Cancer
• Intervention / Treatment: Radiation: Adjuvant Radiotherapy; Radiation: Early Salvage Radiotherapy

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 Type: Interventional
• Enrollment (Actual): 333
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Campbelltown, New South Wales, Australia, 2170
      • Campbelltown Hopsital
    • Camperdown, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital
    • Coffs Harbour, New South Wales, Australia, 2450
      • Coffs Harbour Health Campus, NCCI
    • Darlinghurst, New South Wales, Australia, 2010
      • Radiation Oncology Associates
    • Darlinghurst, New South Wales, Australia
      • St Vincent's Clinic
    • Kingswood, New South Wales, Australia, 2747
      • Nepean Hospital
    • Kogarah, New South Wales, Australia, 2217
      • St George Hospital
    • Liverpool, New South Wales, Australia, 1871
      • Liverpool Hospital
    • Newcastle, New South Wales, Australia, 2310
      • Calvary Mater Newcastle
    • Orange, New South Wales, Australia
      • Central West Cancer Services (Orange Health)
    • Port Macquarie, New South Wales, Australia, 2444
      • Port Macquarie Base Hospital, NCCI
    • St Leonards, New South Wales, Australia, 2065
      • Royal North Shore Hospital
    • Wagga Wagga, New South Wales, Australia, 2650
      • Riverina Cancer Care Centre
    • Wahroonga, New South Wales, Australia, 2076
      • Sydney Adventist Hospital
    • Westmead, New South Wales, Australia, 2145
      • Westmead Hospital
  • Queensland
    • Gold Coast, Queensland, Australia, 4217
      • Radiation Oncology Gold Coast
    • Herston, Queensland, Australia, 4029
      • Royal Brisbane and Women's Hospital
    • Nambour, Queensland, Australia, 4560
      • Oceania Oncology
    • South Brisbane, Queensland, Australia, 4101
      • Radiation Oncology - Mater Centre
    • Toowoomba, Queensland, Australia, 4350
      • Toowoomba Cancer Research Centre
    • Townsville, Queensland, Australia, 4814
      • Townsville Hospital
    • Tugun, Queensland, Australia, 4224
      • Premion
    • Woolloongabba, Queensland, Australia, 4102
      • Princess Alexandra Hospital
  • Victoria
    • East Melbourne, Victoria, Australia, 3002
      • Peter Maccallum Cancer Centre
    • Heidelberg West, Victoria, Australia, 3081
      • Austin Hospital
    • Melbourne, Victoria, Australia, 3004
      • The Alfred/WBRC
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • Fiona Stanley Hospital
    • Nedlands, Western Australia, Australia, 6009
      • Sir Charles Gairdner Hospital
    • Perth, Western Australia, Australia, 6000
      • Royal Perth Hospital
    • Perth, Western Australia, Australia, 6014
      • Perth Radiation Oncology
• New Zealand
  • Auckland, New Zealand
    • Auckland Hospital
  • Christchurch, New Zealand
    • Christchurch Hospital
  • Dunedin, New Zealand, 9016
    • Dunedin Hospital
  • Palmerston North, New Zealand, 4414
    • Palmerston North Hospital
  • Auckland
    • Epsom, Auckland, New Zealand, 1023
      • Auckland Radiation Oncology
  • Wellington
    • Newtown, Wellington, New Zealand, 6021
      • Wellington Hospital

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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 Names: 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 Names: SRT, Surveillance, Radiation

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Time Frame
Quality of Life	Final Analysis will be after 160 events, estimated to be five years after the end of accrual
Toxicity	Final analysis will be after 160 events, estimated to be 5 years after end of accrual.
Anxiety/Depression	Final analysis will be after 160 events, estimated to be 5 years after end of accrual.
Biochemical failure-free survival	Final analysis will be after 160 events, estimated to be 5 years after end of accrual.
Overall survival	Final analysis will be after 160 events, estimated to be 5 years after end of accrual.
Disease-specific survival	Final analysis will be after 160 events, estimated to be 5 years after end of accrual.
Time to distant failure	Final analysis will be after 160 events, estimated to be 5 years after end of accrual.
Time to local failure	Final analysis will be after 160 events, estimated to be 5 years after end of accrual.
Time to the initiation of androgen ablation	Final analysis will be after 160 events, estimated to be 5 years after end of accrual.
Quality adjusted life years	Final analysis will be after 160 events, estimated to be 5 years after end of accrual.
Cost-utility	Final analysis will be after 160 events, estimated to be 5 years after end of accrual.

Collaborators and Investigators

• Sponsor: Trans Tasman Radiation Oncology Group
• Collaborators: Australian and New Zealand Urogenital and Prostate Cancer Trials Group; Urological Society of Australia and New Zealand (USANZ)
• Investigators: Study Chair: Maria Pearse, MBChB, Trans Tasman Radiation Oncology Group; Study Chair: Andrew Kneebone, Trans Tasman Radiation Oncology Group

Publications and helpful links

General Publications

• 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.

Helpful Links

• Trans Tasman Radiation Oncology Group

Study record dates

Study Major Dates

• Study Start (Actual): March 3, 2009
• Primary Completion (Anticipated): December 1, 2022
• Study Completion (Anticipated): December 1, 2026

Study Registration Dates

• First Submitted: March 10, 2009
• First Submitted That Met QC Criteria: March 11, 2009
• First Posted (Estimate): March 12, 2009

Study Record Updates

• Last Update Posted (Actual): November 18, 2022
• Last Update Submitted That Met QC Criteria: November 16, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Prostate Cancer; Radiotherapy; Oncology; Radical Prostatectomy; Prior Radical Prostatectomy (RP); Histological Confirmation of adenocarcinoma of the prostate; Positive margins and/or extraprostatic extension (EPE)
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms
• Other Study ID Numbers: TROG 08.03