Clinical trial NCT01584258: Prostate Advances in Comparative Evidence
Official title: International Randomised Study of Prostatectomy vs Stereotactic Body Radiotherapy (SBRT) and Conventionally Fractionated Radiotherapy vs SBRT for Organ-Confined Prostate Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Prostate Cancer
Keywords: Prostate cancer
Prostate adenocarcinoma
Organ-confined prostate cancer
Low-risk prostate cancer
Intermediate-risk prostate cancer
Lead sponsor: Royal Marsden NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: The Institute of Cancer Research, Sutton, Surrey, UK
First posted: 2012-04-24
Enrollment: 2205
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multicentre, international phase 3 randomised controlled study comprising three parallel randomisations with a common experimental arm.
Primary purpose: TREATMENT

Brief summary: This study is an international multicentre randomised study of low, intermediate, and high risk prostate cancer and is composed of three parallel randomisation schemes based on applicability of surgery as a treatment for the patient and risk group. Low and intermediate risk patients, for whom surgery is a consideration, are randomised to either prostatectomy or prostate SBRT. Low and intermediate risk patients, for whom surgery is not a consideration, are randomised to either conventionally fractionated radiotherapy or prostate SBRT. Intermediate and high risk patients, for whom ADT treatment is indiacted and surgery is not a consideration, are randomised to either conventionally fractionated radiotherapy or prostate SBRT. Efficacy, toxicity and quality of life outcomes will be compared across the pairs in each randomisation.


Eligibility criteria: Inclusion critieria (all arms):

* Histological confirmation of prostate adenocarcinoma within the last 18 months (unless on active surveillance and not clinically indicated)
* Men aged ≥18 years at randomisation
* WHO performance status 0 - 2
* Patients considered candidates for surgery are eligible for PACE-A; patients not considered candidates for surgery and patients who decline surgery or prefer to avoid surgery are eligible for PACE-B and PACE-C.
* Ability of the research subject to understand and the willingness to sign a written informed consent document.

Specific risk stratification inclusion criteria for PACE-A and PACE-B:

* Minimum of 10 biopsy cores.
* Gleason score ≤ 3+4
* Clinical and/or MRI stage T1c -T2c, N0-X, M0-X
* PSA ≤ 20 ng/ml (completed within 60 days of randomisation)
* Patients belonging to one of the following risk groups:
* Low risk - patients with tumours meeting all of the following criteria:

  * Gleason ≤ 6
  * Clinical stage T1-T2a
  * PSA \< 10 ng/ml (within 60 days prior to randomisation)
* Intermediate risk - patients with tumours meeting any one of the following criteria:

  * Gleason 3+4
  * Clinical stage T2b or T2c
  * PSA 10-20 ng/ml (within 60 days prior to randomisation)

Specific risk stratification inclusion criteria for PACE-C:

* Patient planned for a minimum of 6 months ADT (maximum of 12 months). Patients receiving extended androgen deprivation therapy (18 months maximum) to permit safe delay of radiotherapy as a result of the COVID19 pandemic (only) are eligible.
* Gleason score ≤ 4+4
* MRI stage T1c -T3a, N0-X, M0-X
* PSA ≤ 30 ng/ml (within 60 days prior to starting ADT)
* Patients belonging to one of the following risk groups:
* Intermediate risk - includes the presence of any of the following, assuming no high risk features apply:

  * Gleason 7 (3+4 or 4+3)
  * T2 (N0, M0-X)
  * PSA 10-20 ng/ml
* High risk - patients with tumours that meet a maximum of 2 of the following criteria:

  * Gleason 4+4 (max ≤ 50% cores)
  * T3a (N0, M0)
  * PSA \>20 ng/ml

Exclusion criteria (all arms):

* Previous malignancy within the last 2 years (except basal cell carcinoma or squamous cell carcinoma of the skin), or if previous malignancy is expected to significantly compromise 5 year survival.
* Prior pelvic radiotherapy.
* Prior androgen deprivation therapy (including androgen agonists and antagonists) for PACE-A and PACE-B participants.
* Any prior active treatment for prostate cancer (with the exception of ADT for PACE-C participants). Patients previously on active surveillance are eligible if they continue to meet all other eligibility criteria.
* Life expectancy \<5 years.
* Bilateral hip prostheses or any other implants/hardware that would introduce substantial CT artefacts.
* Medical conditions likely to make radiotherapy inadvisable eg inflammatory bowel disease, significant urinary symptoms.
* For patients having fiducials inserted: Anticoagulation with warfarin/ bleeding tendency making fiducial placement or surgery unsafe in the opinion of the clinician.
* Participation in another concurrent treatment protocol for prostate cancer.

Specific exclusion criteria for PACE-C:

* \>14 weeks of androgen deprivation therapy prior to randomisation
* Medical conditions likely to make ADT inadvisable (e.g. significant and ongoing cardiac issues).

Primary outcomes:
measure: PACE-B and PACE-C: Freedom from biochemical or clinical failure
timeFrame: 5 years from randomisation (primary timepoint)
measure: PACE-A: Co-primary patient reported outcomes of urinary incontinence and bowel bother
timeFrame: 2 years from treatment (primary timepoint)
Secondary outcomes:
measure: All arms: Clinician reported acute toxicity
timeFrame: 10 years
measure: All arms: Clinician reported late toxicity
timeFrame: 10 years
measure: All arms: Patient reported acute and late bowel, bladder and erectile dysfunction symptoms.
timeFrame: 10 years
measure: All arms: Disease-specific and overall survival
timeFrame: 10 years
measure: All arms: Progression-free survival
timeFrame: 10 years
measure: PACE-A and PACE-B: Commencement of androgen deprivation therapy; PACE-C: Re-commencement of androgen deprivation therapy
timeFrame: 10 years
measure: PACE-A: Freedom from biochemical or clinical failure
timeFrame: 5 years from randomisation (primary timepoint)
Other outcomes:
Locations:
city: Hamilton
country: Canada
facility: Juravinski Cancer Centre
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Niagara
country: Canada
facility: Walker Family Cancer Centre
state: Ontario
city: Oshawa
country: Canada
facility: Lakeridge Health
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital Cancer Centre
state: Ontario
city: Sudbury
country: Canada
facility: Northeast Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Odette Cancer Centre
state: Ontario
city: Montreal
country: Canada
facility: Hôpital Maisonneuve Rosemont
state: Quebec
city: Montréal
country: Canada
facility: Hôpital Charles-LeMoyne
state: Quebec
city: Dublin
country: Ireland
facility: Beacon Hospital
city: Dublin
country: Ireland
facility: Beaumont Hospital
city: Dublin
country: Ireland
facility: St James's Hospital
city: Dublin
country: Ireland
facility: St. Luke's Hospital
city: Auckland
country: New Zealand
facility: Auckland City Hospital
city: Huntingdon
country: United Kingdom
facility: Hinchingbrooke Hospital
state: Cambridgeshire
city: Colchester
country: United Kingdom
facility: Colchester General Hospital
state: Essex
city: Oxford
country: United Kingdom
facility: Churchill Hospital
state: Oxfordshire
city: London
country: United Kingdom
facility: Mount Vernon Cancer Centre
state: Surrey
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Centre
state: Wales
city: Coventry
country: United Kingdom
facility: University Hospital Coventry & Warwickshire NHS Trust
state: West Midlands
city: Bath
country: United Kingdom
facility: Royal United Hospital
city: Belfast
country: United Kingdom
facility: Belfast City Hospital
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital
city: Boston
country: United Kingdom
facility: Pilgrim Hospital
city: Brighton
country: United Kingdom
facility: Royal Sussex County Hospital
city: Bristol
country: United Kingdom
facility: Bristol Haematology and Oncology Centre
city: Bury
country: United Kingdom
facility: West Suffolk Hospital
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
city: Cambridge
country: United Kingdom
facility: Queen Elizabeth Hospital
city: Canterbury
country: United Kingdom
facility: Kent and Canterbury Hospital
city: Cardiff
country: United Kingdom
facility: Velindre Hospital
city: Cheltenham
country: United Kingdom
facility: Cheltenham General Hospital
city: Derby
country: United Kingdom
facility: Royal Derby Hospital
city: Edinburgh
country: United Kingdom
facility: Western General
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter Hospital
city: Glasgow
country: United Kingdom
facility: The Beatson
city: Guildford
country: United Kingdom
facility: Royal Surrey County Hospital
city: Ipswich
country: United Kingdom
facility: Ipswich Hospital
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
city: Lincoln
country: United Kingdom
facility: Lincoln County Hospital
city: London
country: United Kingdom
facility: Royal Free Hospital
city: London
country: United Kingdom
facility: Imperial College, London
city: London
country: United Kingdom
facility: Charing Cross Hospital
city: London
country: United Kingdom
facility: Guy's Hospital
city: London
country: United Kingdom
facility: North Middlesex University Hospital
city: London
country: United Kingdom
facility: Royal Marsden NHS Foundation Trust
city: London
country: United Kingdom
facility: St Bartholomew's Hospital
city: London
country: United Kingdom
facility: University College Hospital
city: Maidstone
country: United Kingdom
facility: Maidstone Hospital
city: Manchester
country: United Kingdom
facility: Christie Hospital
city: Middlesborough
country: United Kingdom
facility: James Cook University Hospital
city: Newcastle upon Tyne
country: United Kingdom
facility: Freeman Hospital
city: Northampton
country: United Kingdom
facility: Northampton General Hospital
city: Norwich
country: United Kingdom
facility: Norfolk & Norwich Hospital
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital
city: Peterborough
country: United Kingdom
facility: Peterborough City Hospital
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
city: Rhyl
country: United Kingdom
facility: Glan Clwyd Hospital
city: Romford
country: United Kingdom
facility: Queens Hospital
city: Sheffield
country: United Kingdom
facility: Weston Park Hospital
city: Stoke-on-Trent
country: United Kingdom
facility: Royal Stoke University Hospital
city: Sunderland
country: United Kingdom
facility: Sunderland Royal Hospital
city: Sutton In Ashfield
country: United Kingdom
facility: Kings Mill Hospital
city: Torquay
country: United Kingdom
facility: Torbay District General Hospital
city: Truro
country: United Kingdom
facility: Royal Cornwall Hospital
city: Westcliff-on-Sea
country: United Kingdom
facility: Southend University Hospital
city: Wirral
country: United Kingdom
facility: Clatterbridge Cancer Centre
city: Worcester
country: United Kingdom
facility: Worcestershire Royal Hospital
Study officials:
affiliation: Royal Marsden NHS Foundation Trust, London, United Kingdom
name: Nicholas van As, MD
role: STUDY_DIRECTOR
affiliation: Mount Vernon Cancer Centre, United Kingdom
name: Peter Ostler, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Royal Marsden NHS Foundation Trust, London, United Kingdom
name: Alison Tree, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tree AC, Ostler P, van der Voet H, Chu W, Loblaw A, Ford D, Tolan S, Jain S, Martin A, Staffurth J, Armstrong J, Camilleri P, Kancherla K, Frew J, Chan A, Dayes IS, Duffton A, Brand DH, Henderson D, Morrison K, Brown S, Pugh J, Burnett S, Mahmud M, Hinder V, Naismith O, Hall E, van As N; PACE Trial Investigators. Intensity-modulated radiotherapy versus stereotactic body radiotherapy for prostate cancer (PACE-B): 2-year toxicity results from an open-label, randomised, phase 3, non-inferiority trial. Lancet Oncol. 2022 Oct;23(10):1308-1320. doi: 10.1016/S1470-2045(22)00517-4. Epub 2022 Sep 13.
citation: Brand DH, Tree AC, Ostler P, van der Voet H, Loblaw A, Chu W, Ford D, Tolan S, Jain S, Martin A, Staffurth J, Camilleri P, Kancherla K, Frew J, Chan A, Dayes IS, Henderson D, Brown S, Cruickshank C, Burnett S, Duffton A, Griffin C, Hinder V, Morrison K, Naismith O, Hall E, van As N; PACE Trial Investigators. Intensity-modulated fractionated radiotherapy versus stereotactic body radiotherapy for prostate cancer (PACE-B): acute toxicity findings from an international, randomised, open-label, phase 3, non-inferiority trial. Lancet Oncol. 2019 Nov;20(11):1531-1543. doi: 10.1016/S1470-2045(19)30569-8. Epub 2019 Sep 17.