Condition category
Cancer
Date applied
25/02/2015
Date assigned
25/02/2015
Last edited
12/06/2020
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
Recruiting
Publication status
Results overdue

Contact information

Type

Scientific

Primary contact

Ms Stephanie Burnett

ORCID ID

Contact details

ICR Clinical Trials and Statistics Unit (ICR-CTSU)
Division of Clinical Studies
15 Cotswold Road
Sutton
SM2 5NG
United Kingdom
+44 (0)20 8722 4261
pace-icrctsu@icr.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

NCT01584258

Protocol/serial number

12628

Study information

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

Acronym

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

Chelsea NRES, 25/01/12, ref: 11/LO/1915

Study design

Randomised; Interventional; Design type: Treatment

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use contact details to request a patient information sheet

Condition

Topic: Cancer, Surgery; Subtopic: Prostate Cancer, Surgery; Disease: Prostate

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

Phase

Drug names

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 trial start date

01/08/2012

Overall trial end date

01/09/2016

Reason abandoned (if study stopped)

Eligibility

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 type

Patient

Age group

Adult

Gender

Male

Target number of participants

Planned Sample Size: 1716; UK Sample Size: 200

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

Ireland, United Kingdom

Trial participating centre

The Royal Marsden NHS Foundation Trust
Fulham Road
London
SW3 6JJ
United Kingdom

Trial participating centre

East and North Hertfordshire NHS Trust
Mount Vernon Cancer Centre, The Clock Tower, Rickmansworth Road, Northwood
Middlesex
HA6 2RN
United Kingdom

Trial participating centre

Royal Marsden Hospital, Sutton
Downs Rd
Sutton
SM2 5PT
United Kingdom

Trial participating centre

Kingston Hospital
Galsworthy Rd
Kingston upon Thames
KT2 7QB
United Kingdom

Trial participating centre

Churchill Hospital
Old Road Headington
Oxford
OX3 7LE
United Kingdom

Trial participating centre

James Cook University Hospital
Marton Rd
Middlesbrough
TS4 3BW
United Kingdom

Trial participating centre

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

Trial participating centre

Belfast City Hospital
51 Lisburn Rd
Belfast
BT9 7AB
United Kingdom

Trial participating centre

Queen Elizabeth Hospital
Mindelsohn Way Edgbaston
Birmingham
B15 2GW
United Kingdom

Trial participating centre

University Hospital Coventry and Warwickshire
Clifford Bridge Rd
Coventry
CV2 2DX
United Kingdom

Trial participating centre

Addenbrooke's Hospital
Hills Rd
Cambridge
CB2 0QQ
United Kingdom

Trial participating centre

Hinchingbrooke Hospital
Parkway
Hinchingbrooke
PE29 6NT
United Kingdom

Trial participating centre

Sunderland Royal Hospital
Kayll Rd
Sunderland
SR4 7TP
United Kingdom

Trial participating centre

Clatterbridge Cancer Centre
Clatterbridge Rd
Birkenhead
CH63 4JY
United Kingdom

Trial participating centre

West Suffolk Hospital
Hardwick Ln
Bury St Edmunds
IP33 2QZ
United Kingdom

Trial participating centre

Nottingham City Hospital
Hucknall Rd
Nottingham
NG5 1PB
United Kingdom

Trial participating centre

St Bartholomew's Hospital
W Smithfield
London
EC1A 7BE
United Kingdom

Trial participating centre

Leicester Royal Infirmary
Infirmary Square
Leicester
LE1 5WW
United Kingdom

Trial participating centre

Charing Cross Hospital
Fulham Palace Rd Hammersmith
London
W6 8RF
United Kingdom

Trial participating centre

Royal Free Hospital
Pond St Hampstead
London
NW3 2QG
United Kingdom

Trial participating centre

University College Hospital
235 Euston Rd Bloomsbury
London
NW1 2BU
United Kingdom

Trial participating centre

Lincoln County Hospital
Greetwell Rd
Lincoln
LN2 5QY
United Kingdom

Trial participating centre

Pilgrim Hospital
Sibsey Rd
Boston
PE21 9QS
United Kingdom

Trial participating centre

Norfolk & Norwich University Hospital
Colney Ln
Norwich
NR4 7UY
United Kingdom

Trial participating centre

Velindre Cancer Centre
Velindre Rd
Cardiff
CF14 2TL
United Kingdom

Trial participating centre

Glan Clwyd Hospital
Rhuddlan Rd Bodelwyddan
Rhyl
LL18 5UJ
United Kingdom

Trial participating centre

Weston Park Hospital
Whitham Rd Broomhall
Sheffield
S10 2SJ
United Kingdom

Trial participating centre

Beatson West of Scotland Cancer Centre
1053 Great Western Rd
Glasgow
G12 0YN
United Kingdom

Trial participating centre

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

Trial participating centre

Colchester Hospital
Turner Rd Mile End
Colchester
CO4 5JL
United Kingdom

Trial participating centre

Royal Cornwall Hospital
Treliske
Truro
TR1 3LQ
United Kingdom

Trial participating centre

Derriford Hospital
Derriford Rd
Plymouth
PL6 8DH
United Kingdom

Trial participating centre

Torbay Hospital
Newton Rd
Torquay
TQ2 7AA
United Kingdom

Trial participating centre

Bristol Haematology and Oncology Centre
22 Horfield Rd
Bristol
BS2 8ED
United Kingdom

Trial participating centre

Christie Hospital
Wilmslow Rd
Manchester
M20 4BX
United Kingdom

Trial participating centre

The Queen Elizabeth Hospital
Gayton Rd
King's Lynn
PE30 4ET
United Kingdom

Trial participating centre

Western General Hospital
Crewe Rd S
Edinburgh
EH4 2XU
United Kingdom

Trial participating centre

Maidstone Hospital
Hermitage Ln
Maidstone
ME16 9QQ
United Kingdom

Trial participating centre

Musgrove Park Hospital
Parkfield Dr
Taunton
TA1 5DA
United Kingdom

Trial participating centre

North Middlesex University Hospital
Sterling Way
London
N18 1QX
United Kingdom

Trial participating centre

Royal Surrey County Hospital
Egerton Rd
Guildford
GU2 7XX
United Kingdom

Trial participating centre

Beacon Hospital
Beacon Court Bracken Road Sandyford Industrial Estate
Dublin
D18 AK68
Ireland

Trial participating centre

St James's Hospital
James's Street The Liberties
Dublin
D08 NHY1
Ireland

Trial participating centre

Beaumont Hospital
Beaumont Rd
Dublin
D09 V2N0
Ireland

Trial participating centre

St Luke's Hospital
Oakland Drive Highfield Road
Dublin
D06 HH36
Ireland

Trial participating centre

Odette Cancer Centre
Bayview Avenue
Toronto
M4N 3M5
Canada

Trial participating centre

Juravinski Cancer Centre
699 Concession Street
Hamilton
L8V 5C2
Canada

Trial participating centre

Lakeridge Health
1 Hospital Court
Oshawa
L1G 2B9
Canada

Trial participating centre

Northeast Cancer Centre
41 Ramsey Lake Rd
Sudbury
P3E 5J1
Canada

Trial participating centre

Walker Family Cancer Centre
1200 Fourth Ave
St. Catharines
L2S 0A9
Canada

Trial participating centre

Hôpital Charles-LeMoyne
3120 Taschereau Blvd Greenfield Park
Longueuil
J4V 2H1
Canada

Trial participating centre

London Health Sciences Centre
800 Commissioners Rd E
London
N6A 5W9
Canada

Trial participating centre

Ottawa Hospital
501 Smyth Rd
Ottawa
K1H 8L6
Canada

Trial participating centre

Hôpital Maisonneuve-Rosemont
5415 Assumption Blvd
Montreal
H1T 2M4
Canada

Sponsor information

Organisation

Royal Marsden NHS Foundation Trust

Sponsor details

Royal Marsden Hospital
Fulham Road
London
SW3 6JJ
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Industry

Funder name

Accuray Incorporated (USA)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

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.

Intention to publish date

Participant level data

Not provided at time of registration

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

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.