Prostate Advances in Comparative Evidence

Prostate Cancer Clinical Trial

— PACE  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01584258
• Other study ID #: CCR3766
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: August 7, 2012
• Est. completion date: December 2027

Study information

• Verified date: January 2024
• Source: Royal Marsden NHS Foundation Trust
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 2205
• Est. completion date: December 2027
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

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

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

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Royal Marsden NHS Foundation Trust	The Institute of Cancer Research, Sutton, Surrey, UK

Countries where clinical trial is conducted

Canada,  Ireland,  New Zealand,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PACE-B and PACE-C: Freedom from biochemical or clinical failure	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)
Primary	PACE-A: Co-primary patient reported outcomes of urinary incontinence and bowel bother	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	All arms: Clinician reported acute toxicity	CTCAE and RTOG (SBRT and conventional RT patients) or Clavien scale (surgical patients).	10 years
Secondary	All arms: Clinician reported late toxicity	CTCAE and RTOG (SBRT and conventional RT patients only).	10 years
Secondary	All arms: Patient reported acute and late bowel, bladder and erectile dysfunction symptoms.	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
Secondary	All arms: Disease-specific and overall survival	Disease-specific and overall survival	10 years
Secondary	All arms: Progression-free survival	Radiographic, clinical or biochemical evidence of local or distant failure	10 years
Secondary	PACE-A and PACE-B: Commencement of androgen deprivation therapy; PACE-C: Re-commencement of androgen deprivation therapy	LHRH analogues, anti-androgens, orchidectomy	10 years
Secondary	PACE-A: Freedom from biochemical or clinical failure	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)

External Links

•   ICR Clinical Trials Unit - PACE website