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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01584258




Registration number
NCT01584258
Ethics application status
Date submitted
22/04/2012
Date registered
24/04/2012
Date last updated
19/01/2024

Titles & IDs
Public title
Prostate Advances in Comparative Evidence
Scientific title
International Randomised Study of Prostatectomy vs Stereotactic Body Radiotherapy (SBRT) and Conventionally Fractionated Radiotherapy vs SBRT for Organ-Confined Prostate Cancer
Secondary ID [1] 0 0
CCR3766
Universal Trial Number (UTN)
Trial acronym
PACE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prostate Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Surgery - Prostatectomy
Treatment: Other - Conventionally Fractionated Prostate Radiotherapy
Treatment: Other - Prostate SBRT

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.

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.

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.


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

Treatment: Other: 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

Treatment: Other: Prostate SBRT
Prostate SBRT delivered to a dose of 36.25 Gy in 5 fractions.
Intervention code [1] 0 0
Treatment: Surgery
Intervention code [2] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
PACE-B and PACE-C: Freedom from biochemical or clinical failure
Timepoint [1] 0 0
5 years from randomisation (primary timepoint)
Primary outcome [2] 0 0
PACE-A: Co-primary patient reported outcomes of urinary incontinence and bowel bother
Timepoint [2] 0 0
2 years from treatment (primary timepoint)
Secondary outcome [1] 0 0
All arms: Clinician reported acute toxicity
Timepoint [1] 0 0
10 years
Secondary outcome [2] 0 0
All arms: Clinician reported late toxicity
Timepoint [2] 0 0
10 years
Secondary outcome [3] 0 0
All arms: Patient reported acute and late bowel, bladder and erectile dysfunction symptoms.
Timepoint [3] 0 0
10 years
Secondary outcome [4] 0 0
All arms: Disease-specific and overall survival
Timepoint [4] 0 0
10 years
Secondary outcome [5] 0 0
All arms: Progression-free survival
Timepoint [5] 0 0
10 years
Secondary outcome [6] 0 0
PACE-A and PACE-B: Commencement of androgen deprivation therapy; PACE-C: Re-commencement of androgen deprivation therapy
Timepoint [6] 0 0
10 years
Secondary outcome [7] 0 0
PACE-A: Freedom from biochemical or clinical failure
Timepoint [7] 0 0
5 years from randomisation (primary timepoint)

Eligibility
Key inclusion 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
Minimum age
18 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
7/08/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2027
Actual
Sample size
Target
Accrual to date
Final
2205
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
Canada
State/province [1] 0 0
Ontario
Country [2] 0 0
Canada
State/province [2] 0 0
Quebec
Country [3] 0 0
Ireland
State/province [3] 0 0
Dublin
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New Zealand
State/province [4] 0 0
Auckland
Country [5] 0 0
United Kingdom
State/province [5] 0 0
Cambridgeshire
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United Kingdom
State/province [6] 0 0
Essex
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United Kingdom
State/province [7] 0 0
Oxfordshire
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United Kingdom
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Surrey
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United Kingdom
State/province [9] 0 0
Wales
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United Kingdom
State/province [10] 0 0
West Midlands
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United Kingdom
State/province [11] 0 0
Bath
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United Kingdom
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Belfast
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United Kingdom
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Birmingham
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United Kingdom
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Boston
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United Kingdom
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Brighton
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United Kingdom
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Bristol
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United Kingdom
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Bury
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United Kingdom
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Cambridge
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United Kingdom
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Canterbury
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United Kingdom
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Cardiff
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United Kingdom
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Cheltenham
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United Kingdom
State/province [22] 0 0
Derby
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United Kingdom
State/province [23] 0 0
Edinburgh
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United Kingdom
State/province [24] 0 0
Exeter
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United Kingdom
State/province [25] 0 0
Glasgow
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United Kingdom
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Guildford
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United Kingdom
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Ipswich
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United Kingdom
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Leicester
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United Kingdom
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Lincoln
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United Kingdom
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London
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United Kingdom
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Maidstone
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United Kingdom
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Manchester
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United Kingdom
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Middlesborough
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United Kingdom
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Newcastle upon Tyne
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United Kingdom
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Northampton
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United Kingdom
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Norwich
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United Kingdom
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Nottingham
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United Kingdom
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Peterborough
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United Kingdom
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Plymouth
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United Kingdom
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Rhyl
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Romford
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United Kingdom
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Sheffield
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United Kingdom
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Stoke-on-Trent
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United Kingdom
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Sunderland
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United Kingdom
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Sutton In Ashfield
Country [46] 0 0
United Kingdom
State/province [46] 0 0
Torquay
Country [47] 0 0
United Kingdom
State/province [47] 0 0
Truro
Country [48] 0 0
United Kingdom
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Westcliff-on-Sea
Country [49] 0 0
United Kingdom
State/province [49] 0 0
Wirral
Country [50] 0 0
United Kingdom
State/province [50] 0 0
Worcester

Funding & Sponsors
Primary sponsor type
Other
Name
Royal Marsden NHS Foundation Trust
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
The Institute of Cancer Research, Sutton, Surrey, UK
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT01584258
Trial related presentations / publications
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. Erratum In: Lancet Oncol. 2023 May;24(5):e192. doi: 10.1016/S1470-2045(23)00177-8.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Nicholas van As, MD
Address 0 0
Royal Marsden NHS Foundation Trust, London, United Kingdom
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01584258