Prostate Advances in Comparative Evidence

NCT ID: NCT01584258

Last Updated: 2024-01-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

2205 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-08-07

Study Completion Date

2027-12-31

Brief Summary

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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.

Detailed Description

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Conditions

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Prostate Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Multicentre, international phase 3 randomised controlled study comprising three parallel randomisations with a common experimental arm.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type ACTIVE_COMPARATOR

Prostatectomy

Intervention Type PROCEDURE

Radical prostatectomy: performed open, laparoscopically or using a robotically assisted laparoscopic approach.

Prostate SBRT

Intervention Type RADIATION

Prostate SBRT delivered to a dose of 36.25 Gy in 5 fractions.

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.

Group Type ACTIVE_COMPARATOR

Conventionally Fractionated Prostate Radiotherapy

Intervention Type RADIATION

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

Prostate SBRT

Intervention Type RADIATION

Prostate SBRT delivered to a dose of 36.25 Gy in 5 fractions.

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.

Group Type ACTIVE_COMPARATOR

Conventionally Fractionated Prostate Radiotherapy

Intervention Type RADIATION

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

Prostate SBRT

Intervention Type RADIATION

Prostate SBRT delivered to a dose of 36.25 Gy in 5 fractions.

Interventions

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Prostatectomy

Radical prostatectomy: performed open, laparoscopically or using a robotically assisted laparoscopic approach.

Intervention Type PROCEDURE

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

Intervention Type RADIATION

Prostate SBRT

Prostate SBRT delivered to a dose of 36.25 Gy in 5 fractions.

Intervention Type RADIATION

Eligibility Criteria

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Inclusion Criteria

* 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.


* 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)


* 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

* 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.


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

18 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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The Institute of Cancer Research, Sutton, Surrey, UK

UNKNOWN

Sponsor Role collaborator

Royal Marsden NHS Foundation Trust

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Nicholas van As, MD

Role: STUDY_DIRECTOR

Royal Marsden NHS Foundation Trust, London, United Kingdom

Peter Ostler, MD

Role: PRINCIPAL_INVESTIGATOR

Mount Vernon Cancer Centre, United Kingdom

Alison Tree, MD

Role: PRINCIPAL_INVESTIGATOR

Royal Marsden NHS Foundation Trust, London, United Kingdom

Locations

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Northeast Cancer Centre

Greater Sudbury, Ontario, Canada

Site Status

Juravinski Cancer Centre

Hamilton, Ontario, Canada

Site Status

London Health Sciences Centre

London, Ontario, Canada

Site Status

Walker Family Cancer Centre

Niagara, Ontario, Canada

Site Status

Lakeridge Health

Oshawa, Ontario, Canada

Site Status

The Ottawa Hospital Cancer Centre

Ottawa, Ontario, Canada

Site Status

Odette Cancer Centre

Toronto, Ontario, Canada

Site Status

Hôpital Charles-LeMoyne

Montreal, Quebec, Canada

Site Status

Hôpital Maisonneuve Rosemont

Montreal, Quebec, Canada

Site Status

Beacon Hospital

Dublin, , Ireland

Site Status

Beaumont Hospital

Dublin, , Ireland

Site Status

St James's Hospital

Dublin, , Ireland

Site Status

St. Luke's Hospital

Dublin, , Ireland

Site Status

Auckland City Hospital

Auckland, , New Zealand

Site Status

Hinchingbrooke Hospital

Huntingdon, Cambridgeshire, United Kingdom

Site Status

Colchester General Hospital

Colchester, Essex, United Kingdom

Site Status

Churchill Hospital

Oxford, Oxfordshire, United Kingdom

Site Status

Mount Vernon Cancer Centre

London, Surrey, United Kingdom

Site Status

Velindre Cancer Centre

Cardiff, Wales, United Kingdom

Site Status

University Hospital Coventry & Warwickshire NHS Trust

Coventry, West Midlands, United Kingdom

Site Status

Royal United Hospital

Bath, , United Kingdom

Site Status

Belfast City Hospital

Belfast, , United Kingdom

Site Status

Queen Elizabeth Hospital

Birmingham, , United Kingdom

Site Status

Pilgrim Hospital

Boston, , United Kingdom

Site Status

Royal Sussex County Hospital

Brighton, , United Kingdom

Site Status

Bristol Haematology and Oncology Centre

Bristol, , United Kingdom

Site Status

West Suffolk Hospital

Bury, , United Kingdom

Site Status

Addenbrooke's Hospital

Cambridge, , United Kingdom

Site Status

Queen Elizabeth Hospital

Cambridge, , United Kingdom

Site Status

Kent and Canterbury Hospital

Canterbury, , United Kingdom

Site Status

Velindre Hospital

Cardiff, , United Kingdom

Site Status

Cheltenham General Hospital

Cheltenham, , United Kingdom

Site Status

Royal Derby Hospital

Derby, , United Kingdom

Site Status

Western General

Edinburgh, , United Kingdom

Site Status

Royal Devon and Exeter Hospital

Exeter, , United Kingdom

Site Status

The Beatson

Glasgow, , United Kingdom

Site Status

Royal Surrey County Hospital

Guildford, , United Kingdom

Site Status

Ipswich Hospital

Ipswich, , United Kingdom

Site Status

Leicester Royal Infirmary

Leicester, , United Kingdom

Site Status

Lincoln County Hospital

Lincoln, , United Kingdom

Site Status

Royal Free Hospital

London, , United Kingdom

Site Status

Imperial College, London

London, , United Kingdom

Site Status

Charing Cross Hospital

London, , United Kingdom

Site Status

Guy's Hospital

London, , United Kingdom

Site Status

North Middlesex University Hospital

London, , United Kingdom

Site Status

Royal Marsden NHS Foundation Trust

London, , United Kingdom

Site Status

St Bartholomew's Hospital

London, , United Kingdom

Site Status

University College Hospital

London, , United Kingdom

Site Status

Maidstone Hospital

Maidstone, , United Kingdom

Site Status

Christie Hospital

Manchester, , United Kingdom

Site Status

Clatterbridge Cancer Centre

Metropolitan Borough of Wirral, , United Kingdom

Site Status

James Cook University Hospital

Middlesbrough, , United Kingdom

Site Status

Freeman Hospital

Newcastle upon Tyne, , United Kingdom

Site Status

Northampton General Hospital

Northampton, , United Kingdom

Site Status

Norfolk & Norwich Hospital

Norwich, , United Kingdom

Site Status

Nottingham City Hospital

Nottingham, , United Kingdom

Site Status

Peterborough City Hospital

Peterborough, , United Kingdom

Site Status

Derriford Hospital

Plymouth, , United Kingdom

Site Status

Glan Clwyd Hospital

Rhyl, , United Kingdom

Site Status

Queens Hospital

Romford, , United Kingdom

Site Status

Weston Park Hospital

Sheffield, , United Kingdom

Site Status

Royal Stoke University Hospital

Stoke-on-Trent, , United Kingdom

Site Status

Sunderland Royal Hospital

Sunderland, , United Kingdom

Site Status

Kings Mill Hospital

Sutton in Ashfield, , United Kingdom

Site Status

Torbay District General Hospital

Torquay, , United Kingdom

Site Status

Royal Cornwall Hospital

Truro, , United Kingdom

Site Status

Southend University Hospital

Westcliff-on-Sea, , United Kingdom

Site Status

Worcestershire Royal Hospital

Worcester, , United Kingdom

Site Status

Countries

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Canada Ireland New Zealand United Kingdom

References

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Tree AC, Hinder V, Chan A, Tolan S, Ostler P, van der Voet H, Kancherla K, Loblaw A, Naismith O, Jain S, Martin A, Price D, Brand D, Chu W, Duffton A, Kelly P, O'Neill B, Staffurth J, Sasso G, Pugh J, Manning G, Brown S, Burnett S, Griffin C, Hall E, van As N; PACE Investigators. Intensity-modulated moderately hypofractionated radiotherapy versus stereotactic body radiotherapy for prostate cancer (PACE-C): early toxicity results from a randomised, open-label, phase 3, non-inferiority trial. Lancet Oncol. 2025 Jul;26(7):936-947. doi: 10.1016/S1470-2045(25)00205-0. Epub 2025 Jun 12.

Reference Type DERIVED
PMID: 40517778 (View on PubMed)

Smith RP, Mohammed MA, Beriwal S, Benoit RM. Prostate Brachytherapy With Cs-131: Long-term Results Compared With Published Stereotactic Body Radiotherapy Data. Am J Clin Oncol. 2025 Jan 1;48(1):34-37. doi: 10.1097/COC.0000000000001145. Epub 2024 Oct 17.

Reference Type DERIVED
PMID: 39716881 (View on PubMed)

van As N, Griffin C, Tree A, Patel J, Ostler P, van der Voet H, Loblaw A, Chu W, Ford D, Tolan S, Jain S, Camilleri P, Kancherla K, Frew J, Chan A, Naismith O, Armstrong J, Staffurth J, Martin A, Dayes I, Wells P, Price D, Williamson E, Pugh J, Manning G, Brown S, Burnett S, Hall E. Phase 3 Trial of Stereotactic Body Radiotherapy in Localized Prostate Cancer. N Engl J Med. 2024 Oct 17;391(15):1413-1425. doi: 10.1056/NEJMoa2403365.

Reference Type DERIVED
PMID: 39413377 (View on PubMed)

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.

Reference Type DERIVED
PMID: 36113498 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31540791 (View on PubMed)

Other Identifiers

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CCR3766

Identifier Type: -

Identifier Source: org_study_id

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