Clinical trial NCT00860652: Radiotherapy - Adjuvant Versus Early Salvage
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.
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Prostate Cancer
Keywords: Oncology
Prostate Cancer
Radiotherapy
Radical Prostatectomy
Prior Radical Prostatectomy (RP)
Histological Confirmation of adenocarcinoma of the prostate
Positive margins and/or extraprostatic extension (EPE)
Lead sponsor: Trans Tasman Radiation Oncology Group
Sponsor class: OTHER
Collaborators: name: Urological Society of Australia and New Zealand (USANZ)
name: Australian and New Zealand Urogenital and Prostate Cancer Trials Group
First posted: 2009-03-12
Enrollment: 333
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Biochemical failure: PSA ≥ 0.4 ng/ml and rising following RT
timeFrame: After 160 events have been observed, expected to be 5 years after recruitment closes
Secondary outcomes:
measure: Quality of Life
timeFrame: Final Analysis will be after 160 events, estimated to be five years after the end of accrual
measure: Toxicity
timeFrame: Final analysis will be after 160 events, estimated to be 5 years after end of accrual.
measure: Anxiety/Depression
timeFrame: Final analysis will be after 160 events, estimated to be 5 years after end of accrual.
measure: Biochemical failure-free survival
timeFrame: Final analysis will be after 160 events, estimated to be 5 years after end of accrual.
measure: Overall survival
timeFrame: Final analysis will be after 160 events, estimated to be 5 years after end of accrual.
measure: Disease-specific survival
timeFrame: Final analysis will be after 160 events, estimated to be 5 years after end of accrual.
measure: Time to distant failure
timeFrame: Final analysis will be after 160 events, estimated to be 5 years after end of accrual.
measure: Time to local failure
timeFrame: Final analysis will be after 160 events, estimated to be 5 years after end of accrual.
measure: Time to the initiation of androgen ablation
timeFrame: Final analysis will be after 160 events, estimated to be 5 years after end of accrual.
measure: Quality adjusted life years
timeFrame: Final analysis will be after 160 events, estimated to be 5 years after end of accrual.
measure: Cost-utility
timeFrame: Final analysis will be after 160 events, estimated to be 5 years after end of accrual.
Other outcomes:
Locations:
city: Campbelltown
country: Australia
facility: Campbelltown Hopsital
state: New South Wales
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Coffs Harbour
country: Australia
facility: Coffs Harbour Health Campus, NCCI
state: New South Wales
city: Darlinghurst
country: Australia
facility: Radiation Oncology Associates
state: New South Wales
city: Darlinghurst
country: Australia
facility: St Vincent's Clinic
state: New South Wales
city: Kingswood
country: Australia
facility: Nepean Hospital
state: New South Wales
city: Kogarah
country: Australia
facility: St George Hospital
state: New South Wales
city: Liverpool
country: Australia
facility: Liverpool Hospital
state: New South Wales
city: Newcastle
country: Australia
facility: Calvary Mater Newcastle
state: New South Wales
city: Orange
country: Australia
facility: Central West Cancer Services (Orange Health)
state: New South Wales
city: Port Macquarie
country: Australia
facility: Port Macquarie Base Hospital, NCCI
state: New South Wales
city: St Leonards
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Wagga Wagga
country: Australia
facility: Riverina Cancer Care Centre
state: New South Wales
city: Wahroonga
country: Australia
facility: Sydney Adventist Hospital
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Gold Coast
country: Australia
facility: Radiation Oncology Gold Coast
state: Queensland
city: Herston
country: Australia
facility: Royal Brisbane and Women's Hospital
state: Queensland
city: Nambour
country: Australia
facility: Oceania Oncology
state: Queensland
city: South Brisbane
country: Australia
facility: Radiation Oncology - Mater Centre
state: Queensland
city: Toowoomba
country: Australia
facility: Toowoomba Cancer Research Centre
state: Queensland
city: Townsville
country: Australia
facility: Townsville Hospital
state: Queensland
city: Tugun
country: Australia
facility: Premion
state: Queensland
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: East Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Heidelberg West
country: Australia
facility: Austin Hospital
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred/WBRC
state: Victoria
city: Murdoch
country: Australia
facility: Fiona Stanley Hospital
state: Western Australia
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: Perth
country: Australia
facility: Royal Perth Hospital
state: Western Australia
city: Perth
country: Australia
facility: Perth Radiation Oncology
state: Western Australia
city: Epsom
country: New Zealand
facility: Auckland Radiation Oncology
state: Auckland
city: Newtown
country: New Zealand
facility: Wellington Hospital
state: Wellington
city: Auckland
country: New Zealand
facility: Auckland Hospital
city: Christchurch
country: New Zealand
facility: Christchurch Hospital
city: Dunedin
country: New Zealand
facility: Dunedin Hospital
city: Palmerston North
country: New Zealand
facility: Palmerston North Hospital
Study officials:
affiliation: Trans Tasman Radiation Oncology Group
name: Maria Pearse, MBChB
role: STUDY_CHAIR
affiliation: Trans Tasman Radiation Oncology Group
name: Andrew Kneebone
role: STUDY_CHAIR
References:
citation: 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.