Prostate Advances in Comparative Evidence (PACE)

January 18, 2024 updated by: Royal Marsden NHS Foundation Trust

International Randomised Study of Prostatectomy vs Stereotactic Body Radiotherapy (SBRT) and Conventionally Fractionated Radiotherapy vs SBRT for Organ-Confined Prostate Cancer

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

2205

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Hamilton, Ontario, Canada
        • Juravinski Cancer Centre
      • London, Ontario, Canada
        • London Health Sciences Centre
      • Niagara, Ontario, Canada
        • Walker Family Cancer Centre
      • Oshawa, Ontario, Canada
        • Lakeridge Health
      • Ottawa, Ontario, Canada
        • The Ottawa Hospital Cancer Centre
      • Sudbury, Ontario, Canada
        • Northeast Cancer Centre
      • Toronto, Ontario, Canada
        • Odette Cancer Centre
    • Quebec
      • Montreal, Quebec, Canada
        • Hopital Maisonneuve Rosemont
      • Montréal, Quebec, Canada
        • Hopital Charles-LeMoyne
  • Ireland
      • Dublin, Ireland
        • Beaumont Hospital
      • Dublin, Ireland
        • St James's Hospital
      • Dublin, Ireland
        • Beacon Hospital
      • Dublin, Ireland
        • St. Luke's Hospital
  • New Zealand
      • Auckland, New Zealand
        • Auckland City Hospital
  • United Kingdom
      • Bath, United Kingdom
        • Royal United Hospital
      • Belfast, United Kingdom
        • Belfast City Hospital
      • Birmingham, United Kingdom
        • Queen Elizabeth Hospital
      • Boston, United Kingdom
        • Pilgrim Hospital
      • Brighton, United Kingdom
        • Royal Sussex County Hospital
      • Bristol, United Kingdom
        • Bristol Haematology and Oncology Centre
      • Bury, United Kingdom
        • West Suffolk Hospital
      • Cambridge, United Kingdom
        • Addenbrooke's Hospital
      • Cambridge, United Kingdom
        • Queen Elizabeth Hospital
      • Canterbury, United Kingdom
        • Kent and Canterbury Hospital
      • Cardiff, United Kingdom
        • Velindre Hospital
      • Cheltenham, United Kingdom
        • Cheltenham General Hospital
      • Derby, United Kingdom
        • Royal Derby Hospital
      • Edinburgh, United Kingdom
        • Western General
      • Exeter, United Kingdom
        • Royal Devon and Exeter Hospital
      • Glasgow, United Kingdom
        • The Beatson
      • Guildford, United Kingdom
        • Royal Surrey County Hospital
      • Ipswich, United Kingdom
        • Ipswich Hospital
      • Leicester, United Kingdom
        • Leicester Royal Infirmary
      • Lincoln, United Kingdom
        • Lincoln County Hospital
      • London, United Kingdom
        • Charing Cross Hospital
      • London, United Kingdom
        • North Middlesex University Hospital
      • London, United Kingdom, NW3 2QC
        • Royal Free Hospital
      • London, United Kingdom
        • University College Hospital
      • London, United Kingdom
        • St Bartholomew'S Hospital
      • London, United Kingdom
        • Guy's Hospital
      • London, United Kingdom
        • Royal Marsden NHS Foundation Trust
      • London, United Kingdom, W12 0NN
        • Imperial College, London
      • Maidstone, United Kingdom
        • Maidstone Hospital
      • Manchester, United Kingdom
        • Christie Hospital
      • Middlesborough, United Kingdom
        • James Cook University Hospital
      • Newcastle upon Tyne, United Kingdom
        • Freeman Hospital
      • Northampton, United Kingdom
        • Northampton General Hospital
      • Norwich, United Kingdom
        • Norfolk & Norwich Hospital
      • Nottingham, United Kingdom
        • Nottingham City Hospital
      • Peterborough, United Kingdom
        • Peterborough City Hospital
      • Plymouth, United Kingdom
        • Derriford Hospital
      • Rhyl, United Kingdom
        • Glan Clwyd Hospital
      • Romford, United Kingdom
        • Queens Hospital
      • Sheffield, United Kingdom
        • Weston Park Hospital
      • Stoke-on-Trent, United Kingdom
        • Royal Stoke University Hospital
      • Sunderland, United Kingdom
        • Sunderland Royal Hospital
      • Sutton In Ashfield, United Kingdom
        • Kings Mill Hospital
      • Torquay, United Kingdom
        • Torbay District General Hospital
      • Truro, United Kingdom
        • Royal Cornwall Hospital
      • Westcliff-on-Sea, United Kingdom
        • Southend University Hospital
      • Wirral, United Kingdom
        • Clatterbridge Cancer Centre
      • Worcester, United Kingdom
        • Worcestershire Royal Hospital
    • Cambridgeshire
      • Huntingdon, Cambridgeshire, United Kingdom, PE29 6NT
        • Hinchingbrooke Hospital
    • Essex
      • Colchester, Essex, United Kingdom, CO4 5JL
        • Colchester General Hospital
    • Oxfordshire
      • Oxford, Oxfordshire, United Kingdom
        • Churchill Hospital
    • Surrey
      • London, Surrey, United Kingdom, HA6 2RN
        • Mount Vernon Cancer Centre
    • Wales
      • Cardiff, Wales, United Kingdom, CF14 2TL
        • Velindre Cancer Centre
    • West Midlands
      • Coventry, West Midlands, United Kingdom, CV2 2DX
        • University Hospital Coventry & Warwickshire NHS Trust

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: PACE-A: Prostatectomy vs prostate SBRT
Low and intermediate risk patients, for whom surgery is considered, will be randomised to prostatectomy vs prostate SBRT delivered with 36.25 Gy in 5 fractions.
Radiation: Prostate SBRT
Prostate SBRT delivered to a dose of 36.25 Gy in 5 fractions.
Procedure: Prostatectomy
Radical prostatectomy: performed open, laparoscopically or using a robotically assisted laparoscopic approach.
Active Comparator: PACE-B: Conventionally Fractionated RT vs Prostate SBRT
Low and intermediate risk patients, for whom surgery is not considered or who refuse surgery, will be randomised to either conventionally fractionated radiotherapy delivered to a dose of 78 Gy in 39 fractions or 62 Gy in 20 fractions vs SBRT delivered with 36.25 Gy in 5 fractions.
Radiation: Prostate SBRT
Prostate SBRT delivered to a dose of 36.25 Gy in 5 fractions.
Radiation: Conventionally Fractionated Prostate Radiotherapy

Conventional fractionation delivered to a dose of:

(PACE-B) 78 Gy in 39 fractions or 62 Gy in 20 fractions; (PACE-C) 60 Gy in 20 fractions
Active Comparator: PACE-C: Conventionally Fractionated RT vs Prostate SBRT
Intermediate and high risk patients, indicated for 6 months ADT, will be randomised to either conventionally fractionated radiotherapy delivered to a dose of 60 Gy in 20 fractions vs SBRT delivered with 36.25 Gy in 5 fractions.
Radiation: Prostate SBRT
Prostate SBRT delivered to a dose of 36.25 Gy in 5 fractions.
Radiation: Conventionally Fractionated Prostate Radiotherapy

Conventional fractionation delivered to a dose of:

(PACE-B) 78 Gy in 39 fractions or 62 Gy in 20 fractions; (PACE-C) 60 Gy in 20 fractions

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
PACE-B and PACE-C: Freedom from biochemical or clinical failure
Time Frame: 5 years from randomisation (primary timepoint)

Biochemical progression is defined as: Phoenix definition

Clinical progression is defined as: commencement (PACE-B) or re-commencement (PACE-C) of androgen deprivation therapy, local recurrence, nodal recurrence and distant metastases
5 years from randomisation (primary timepoint)
PACE-A: Co-primary patient reported outcomes of urinary incontinence and bowel bother
Time Frame: 2 years from treatment (primary timepoint)

Urinary incontinence assessed by the number of absorbent pads required per day to control leakage measured by The Expanded Prostate Cancer Index (EPIC) questionnaire.

Bowel bother assessed by summary score from the EPIC questionnaire.
2 years from treatment (primary timepoint)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
All arms: Clinician reported acute toxicity
Time Frame: 10 years
CTCAE and RTOG (SBRT and conventional RT patients) or Clavien scale (surgical patients).
10 years
All arms: Clinician reported late toxicity
Time Frame: 10 years
CTCAE and RTOG (SBRT and conventional RT patients only).
10 years
All arms: Patient reported acute and late bowel, bladder and erectile dysfunction symptoms.
Time Frame: 10 years
Assessed using International Index of Erectile Function-5 (IIEF-5), International Prostate Symptom Score (IPSS), Vaizey score, and Expanded Prostate Index Composite-26 (EPIC-26) instruments.
10 years
All arms: Disease-specific and overall survival
Time Frame: 10 years
Disease-specific and overall survival
10 years
All arms: Progression-free survival
Time Frame: 10 years
Radiographic, clinical or biochemical evidence of local or distant failure
10 years
PACE-A and PACE-B: Commencement of androgen deprivation therapy; PACE-C: Re-commencement of androgen deprivation therapy
Time Frame: 10 years
LHRH analogues, anti-androgens, orchidectomy
10 years
PACE-A: Freedom from biochemical or clinical failure
Time Frame: 5 years from randomisation (primary timepoint)

Biochemical progression is defined as: Phoenix definition (SBRT arm) or >0.2ng/ml (surgical arm)

Clinical progression is defined as: commencement of androgen deprivation therapy, local recurrence, nodal recurrence and distant metastases
5 years from randomisation (primary timepoint)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Royal Marsden NHS Foundation Trust

Collaborators

The Institute of Cancer Research, Sutton, Surrey, UK

Investigators

  • Study Director: Nicholas van As, MD, Royal Marsden NHS Foundation Trust, London, United Kingdom
  • Principal Investigator: Peter Ostler, MD, Mount Vernon Cancer Centre, United Kingdom
  • Principal Investigator: Alison Tree, MD, Royal Marsden NHS Foundation Trust, London, United Kingdom

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 7, 2012

Primary Completion (Estimated)

December 1, 2025

Study Completion (Estimated)

December 1, 2027

Study Registration Dates

First Submitted

April 22, 2012

First Submitted That Met QC Criteria

April 22, 2012

First Posted (Estimated)

April 24, 2012

Study Record Updates

Last Update Posted (Estimated)

January 19, 2024

Last Update Submitted That Met QC Criteria

January 18, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CCR3766

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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