The PACE Study

ISRCTN	ISRCTN17627211
DOI	https://doi.org/10.1186/ISRCTN17627211
ClinicalTrials.gov number	NCT01584258
Secondary identifying numbers	12628

Submission date: 25/02/2015
Registration date: 25/02/2015
Last edited: 28/02/2023

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English Summary

https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-comparing-surgery-conventional-radiotherapy-and-stereotactic-radiotherapy-for-localised-prostate-cancer-pace

Contact information

Ms Stephanie Burnett
Scientific

ICR Clinical Trials and Statistics Unit (ICR-CTSU)
Division of Clinical Studies
15 Cotswold Road
Sutton
SM2 5NG
United Kingdom

Phone	+44 (0)20 8722 4261
Email	pace-icrctsu@icr.ac.uk

Study information

Study design	Randomised; Interventional; Design type: Treatment
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use contact details to request a patient information sheet
Scientific title	International randomised study of laparoscopic prostatectomy vs stereotactic body radiotherapy (SBRT) and conventionally fractionated radiotherapy vs SBRT for early stage organ-confined prostate cancer
Study hypothesis	The aim of this study is to assess whether hypofractionated stereotactic body radiotherapy (SBRT) offers therapeutic benefit over prostatectomy or conventionally fractionated radiotherapy for people with early stage organ-confined prostate cancer. Profound hypofractionation with SBRT has the potential to achieve equivalent tumour control rates compared to surgery and conventional radiotherapy while reducing radiation to normal tissues (bladder, rectal and penile bulb) and minimising radiation-induced side effects.
Ethics approval(s)	Chelsea NRES, 25/01/12, ref: 11/LO/1915
Condition	Prostate cancer
Intervention	Current intervention as of 17/02/2020: 1. Radiotherapy: Conventionally fractionated radiotherapy: delivered to a dose of 60 Gy in 20 fractions (PACE-C) or 62 Gy in 20 fractions (PACE-B) 2. SBRT - hypofractionated stereotactic body radiotherapy: delivered to a dose of 36.25 Gy in 5 fractions 3. Surgery: prostatectomy surgery In PACE-A low- and intermediate-risk patients will be randomised between surgery (control) and SBRT. In PACE-B low- and intermediate-risk patients will be randomised between radiotherapy (control) and SBRT. In PACE-C intermediate- and high-risk patients will be randomised between radiotherapy (control) and SBRT. Previous intervention: 1. Radiotherapy: Conventionally fractionated radiotherapy: delivered to a dose of 78 Gy in 2 Gy fractions 2. SBRT - hypofractionated stereotactic body radiotherapy: delivered to a dose of 36.25 Gy in 5 fractions 3. Surgery: laparoscopic prostatectomy
Intervention type	Procedure/Surgery
Primary outcome measure	Current primary outcome measures as of 17/02/2020: For PACE-A (surgery vs SBRT cohort): 1. Urinary incontinence (number of absorbent pads required per day to control leakage) measured by the Expanded Prostate Cancer Index (EPIC) questionnaire at 2 years post-treatment 2. Bowel bother summary score from the EPIC questionnaire at 2 years post-treatment For PACE-B and PACE-C (conventionally fractionated radiotherapy vs SBRT cohorts): Freedom from biochemical (Phoenix definition) or clinical (commencement [PACE‐B] or re‐commencement [PACE‐C] of androgen deprivation therapy, local recurrence, nodal recurrence and distant metastases) failure at 5 years post-randomisation Previous primary outcome measures: Biochemical progression-free survival: Phoenix definition for conventional radiotherapy and SBRT arms, >0.2 ng/ml for surgical arm. The main time point of interest is 5 years post treatment.
Secondary outcome measures	Current secondary outcome measures as of 17/02/2020: For PACE-A: Freedom from biochemical (Phoenix definition for SBRT arm, >0.2 ng/ml for surgical arm) or clinical (commencement of androgen deprivation therapy, local recurrence, nodal recurrence and distant metastases) failure at 5 years post-treatment For all cohorts: 1. Toxicity assessment for surgical and SBRT arm: CTCAE and RTOG for acute and late toxicity. Clavien scale used to assess acute post-surgical complications for surgical patients only. 2. Toxicity assessment for conventionally fractionated and SBRT arm: CTCAE and RTOG acute and late toxicity scoring 3. Patient reported outcomes and quality of life assessment for all treatment arms: erectile function (IIEF-5), IPSS, Vaizey score, EPIC-26 and PR-25 4. Disease-specific and overall survival 5. Progression-free survival: radiographic, clinical or biochemical evidence of local or distant failure 6. Commencement (PACE-A and PACE-B)/recommencement (PACE-C) of androgen deprivation therapy ( LHRH analogues, anti-androgens, orchidectomy) Previous secondary outcome measures: 1. Toxicity assessment for surgical and SBRT arm: CTCAE and RTOG for acute and late toxicity. Clavien scale used to assess acute post-surgical complications for surgical patients only. 2. Toxicity assessment for conventionally fractionated and SBRT arm: CTCAE and RTOG acute and late toxicity scoring 3. Patient reported outcomes and quality of life assessment for all treatment arms: Erectile function (IIEF-5), IPSS, Vaizey score, EPIC-26 and PR-25. 4. Disease-specific and overall survival 5. Progression-free survival: radiographic, clinical or biochemical evidence of local or distant failure. 6. Commencement of androgen deprivation therapy ( LHRH analogues, anti-androgens, orchidectomy).
Overall study start date	01/08/2012
Overall study end date	01/09/2016

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Male
Target number of participants	Planned Sample Size: 1716; UK Sample Size: 200
Participant inclusion criteria	1. Histological confirmation of prostate adenocarcinoma with a minimum of 10 biopsy cores taken within last 18 months. 2. Gleason score = 3+4 3. Men aged at least18 4. Clinical and MRI stage T1c –T2c, N0-X, M0-X 5. PSA = 20 ng/ml 6. Pre-enrollment PSA must be completed within 60 days of registration 7. Patients belonging in one of the following risk groups according to the National Comprehensive Cancer Network (www.nccn.org): 7.1. Low risk: Clinical stage T1-T2a and Gleason = 6 and PSA < 10 ng/ml, or 7.2. Intermediate risk includes any one of the following: 7.2.1. Clinical stage T2b orT2c 7.2.2. PSA 10-20 ng/ml 7.2.3. Gleason 7 8. WHO performance status 0 - 2 9. Prostate volume = 90 cc measured within 6 months of randomisation 10. Ability of the research subject to understand and the willingness to sign a written informed consent document
Participant exclusion criteria	1. Clinical stage T3 or greater 2. Gleason score = 4 + 3 3. High risk disease defined by National Comprehensive Cancer Network (www.nccn.org) 4. < 10 prostate biopsies taken 5. Previous malignancy within last 5 years except basal cell carcinoma or squamous cell carcinoma of the skin 6. Prior pelvic radiotherapy 7. Prior androgen deprivation therapy (including androgen agonists and antagonists) 8. Any prior active treatment for prostate cancer. Patients previously on active surveillance are eligible if they continue to meet all other eligibility criteria. 9. Prior transurethral resection of the prostate (TURP) for benign prostatic hypertrophy 10. Life expectancy <5 years 11. Bilateral hip prostheses or any other implants/hardware that would introduce substantial CT artifacts 12. Medical conditions likely to make radiotherapy inadvisable eg inflammatory bowel disease, significant urinary symptoms 13. Anticoagulation with warfarin/bleeding tendency making fiducial placement or surgery unsafe in the opinion of the clinician. 14. Medical condition/ implant that prohibits MRI 15. Participation in another concurrent treatment protocol
Recruitment start date	01/08/2012
Recruitment end date	31/12/2022

Locations

Countries of recruitment

Canada
England
Ireland
Northern Ireland
Scotland
United Kingdom
Wales

Study participating centres

The Royal Marsden NHS Foundation Trust

Fulham Road
London
SW3 6JJ
United Kingdom

East and North Hertfordshire NHS Trust

Mount Vernon Cancer Centre
The Clock Tower
Rickmansworth Road
Northwood
Middlesex
HA6 2RN
United Kingdom

Royal Marsden Hospital, Sutton

Downs Rd
Sutton
SM2 5PT
United Kingdom

Kingston Hospital

Galsworthy Rd
Kingston upon Thames
KT2 7QB
United Kingdom

Churchill Hospital

Old Road
Headington
Oxford
OX3 7LE
United Kingdom

James Cook University Hospital

Marton Rd
Middlesbrough
TS4 3BW
United Kingdom

Freeman Hospital

Freeman Rd
High Heaton
Newcastle upon Tyne
NE7 7DN
United Kingdom

Belfast City Hospital

51 Lisburn Rd
Belfast
BT9 7AB
United Kingdom

Queen Elizabeth Hospital

Mindelsohn Way
Edgbaston
Birmingham
B15 2GW
United Kingdom

University Hospital Coventry and Warwickshire

Clifford Bridge Rd
Coventry
CV2 2DX
United Kingdom

Addenbrooke's Hospital

Hills Rd
Cambridge
CB2 0QQ
United Kingdom

Hinchingbrooke Hospital

Parkway
Hinchingbrooke
PE29 6NT
United Kingdom

Sunderland Royal Hospital

Kayll Rd
Sunderland
SR4 7TP
United Kingdom

Clatterbridge Cancer Centre

Clatterbridge Rd
Birkenhead
CH63 4JY
United Kingdom

West Suffolk Hospital

Hardwick Ln
Bury St Edmunds
IP33 2QZ
United Kingdom

Nottingham City Hospital

Hucknall Rd
Nottingham
NG5 1PB
United Kingdom

St Bartholomew's Hospital

W Smithfield
London
EC1A 7BE
United Kingdom

Leicester Royal Infirmary

Infirmary Square
Leicester
LE1 5WW
United Kingdom

Charing Cross Hospital

Fulham Palace Rd
Hammersmith
London
W6 8RF
United Kingdom

Royal Free Hospital

Pond St
Hampstead
London
NW3 2QG
United Kingdom

University College Hospital

235 Euston Rd
Bloomsbury
London
NW1 2BU
United Kingdom

Lincoln County Hospital

Greetwell Rd
Lincoln
LN2 5QY
United Kingdom

Pilgrim Hospital

Sibsey Rd
Boston
PE21 9QS
United Kingdom

Norfolk & Norwich University Hospital

Colney Ln
Norwich
NR4 7UY
United Kingdom

Velindre Cancer Centre

Velindre Rd
Cardiff
CF14 2TL
United Kingdom

Glan Clwyd Hospital

Rhuddlan Rd
Bodelwyddan
Rhyl
LL18 5UJ
United Kingdom

Weston Park Hospital

Whitham Rd
Broomhall
Sheffield
S10 2SJ
United Kingdom

Beatson West of Scotland Cancer Centre

1053 Great Western Rd
Glasgow
G12 0YN
United Kingdom

Southend University Hospital

Prittlewell Chase
Westcliff-on-Sea
Southend-on-Sea
SS0 0RY
United Kingdom

Colchester Hospital

Turner Rd
Mile End
Colchester
CO4 5JL
United Kingdom

Royal Cornwall Hospital

Treliske
Truro
TR1 3LQ
United Kingdom

Derriford Hospital

Derriford Rd
Plymouth
PL6 8DH
United Kingdom

Torbay Hospital

Newton Rd
Torquay
TQ2 7AA
United Kingdom

Bristol Haematology and Oncology Centre

22 Horfield Rd
Bristol
BS2 8ED
United Kingdom

Christie Hospital

Wilmslow Rd
Manchester
M20 4BX
United Kingdom

The Queen Elizabeth Hospital

Gayton Rd
King's Lynn
PE30 4ET
United Kingdom

Western General Hospital

Crewe Rd S
Edinburgh
EH4 2XU
United Kingdom

Maidstone Hospital

Hermitage Ln
Maidstone
ME16 9QQ
United Kingdom

Musgrove Park Hospital

Parkfield Dr
Taunton
TA1 5DA
United Kingdom

North Middlesex University Hospital

Sterling Way
London
N18 1QX
United Kingdom

Royal Surrey County Hospital

Egerton Rd
Guildford
GU2 7XX
United Kingdom

Beacon Hospital

Beacon Court
Bracken Road
Sandyford Industrial Estate
Dublin
D18 AK68
Ireland

St James's Hospital

James's Street
The Liberties
Dublin
D08 NHY1
Ireland

Beaumont Hospital

Beaumont Rd
Dublin
D09 V2N0
Ireland

St Luke's Hospital

Oakland Drive
Highfield Road
Dublin
D06 HH36
Ireland

Odette Cancer Centre

Bayview Avenue
Toronto
M4N 3M5
Canada

Juravinski Cancer Centre

699 Concession Street
Hamilton
L8V 5C2
Canada

Lakeridge Health

1 Hospital Court
Oshawa
L1G 2B9
Canada

Northeast Cancer Centre

41 Ramsey Lake Rd
Sudbury
P3E 5J1
Canada

Walker Family Cancer Centre

1200 Fourth Ave
St. Catharines
L2S 0A9
Canada

Hôpital Charles-LeMoyne

3120 Taschereau Blvd
Greenfield Park
Longueuil
J4V 2H1
Canada

London Health Sciences Centre

800 Commissioners Rd E
London
N6A 5W9
Canada

Ottawa Hospital

501 Smyth Rd
Ottawa
K1H 8L6
Canada

Hôpital Maisonneuve-Rosemont

5415 Assumption Blvd
Montreal
H1T 2M4
Canada

Sponsor information

Royal Marsden NHS Foundation Trust
Hospital/treatment centre

Royal Marsden Hospital
Fulham Road
London
SW3 6JJ
England
United Kingdom

"ROR"	https://ror.org/0008wzh48

Funders

Funder type

Industry

Accuray Incorporated (USA)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	The main trial results will be published in a peer-reviewed journal, on behalf of all collaborators. The manuscript will be prepared by a writing group, consisting of members of the Trial Management Group, and participating clinicians. All participating clinicians will be acknowledged in the publication. All presentations and publications relating to the trial must be authorised by the Trial Management Group. Authorship of any secondary publications, e.g, will reflect the intellectual and time input into these studies. No Investigator may present or attempt to publish data relating to the PACE trial without prior permission from the Trial Management Group.
IPD sharing plan	Not provided at time of registration

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Interim results article	acute toxicity findings	01/11/2019	20/06/2022	Yes	No
Plain English results			28/02/2023	No	Yes

Editorial Notes

28/02/2023: Results in plain English uploaded to the trial outputs table.
20/06/2022: Publication reference added.
01/02/2021: The condition has been changed from "Topic: Cancer, Surgery; Subtopic: Prostate Cancer, Surgery; Disease: Prostate" to "Prostate cancer" following a request from the NIHR.
12/06/2020: Updated contact details.
17/02/2020: The following changes have been made:
1. The intervention has been changed.
2. The primary outcome measures have been changed.
3. The secondary outcome measures have been changed.
4. The recruitment end date has been changed from 01/09/2016 to 31/12/2022.
5. Royal Marsden Hospital Sutton, Kingston Hospital, Churchill Hospital, James Cook University Hospital, Freeman Hospital, Belfast City Hospital, Queen Elizabeth Hospital, University Hospital Coventry and Warwickshire, Addenbrooke's Hospital, Hinchingbrooke Hospital, Sunderland Royal Hospital, Clatterbridge Cancer Centre, West Suffolk Hospital, Nottingham City Hospital, St Bartholomew's Hospital, Leicester Royal Infirmary, Charing Cross Hospital, Royal Free Hospital, University College Hospital, Lincoln County Hospital, Pilgrim Hospital, Norfolk & Norwich University Hospital, Velindre Cancer Centre, Glan Clwyd Hospital, Weston Park Hospital, Beatson West of Scotland Cancer Centre, Southend University Hospital, Colchester Hospital, Royal Cornwall Hospital, Derriford Hospital, Torbay Hospital, Bristol Haematology and Oncology Centre, Christie Hospital, The Queen Elizabeth Hospital, Western General Hospital, Maidstone Hospital, Musgrove Park Hospital, North Middlesex University Hospital, Royal Surrey County Hospital, Beacon Hospital, St James's Hospital, Beaumont Hospital, St Luke's Hospital, Odette Cancer Centre, Juravinski Cancer Centre, Lakeridge Health, Northeast Cancer Centre, Walker Family Cancer Centre, Hôpital Charles-LeMoyne, London Health Sciences Centre, Ottawa Hospital and Hôpital Maisonneuve-Rosemont have been added to the trial participating centres.
10/04/2019: Publication reference added.