Clinical trial NCT05613023: A Trial of 5 Fraction Prostate SBRT Versus 5 Fraction Prostate and Pelvic Nodal SBRT
Official title: PACE-NODES. A Phase III Randomised Trial of 5 Fraction Prostate SBRT Versus 5 Fraction Prostate and Pelvic Nodal SBRT
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Prostate Cancer
Lead sponsor: Institute of Cancer Research, United Kingdom
Sponsor class: OTHER
Collaborators: name: Prostate Cancer UK
First posted: 2022-11-14
Enrollment: 1128
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will compare the safety and efficacy of curative radiotherapy to the prostate and lymph glands given in 5 visits to that of prostate alone radiotherapy given in 5 visits, in men with high risk localised prostate cancer.

Detailed description: This study will look at the safety of curative radiotherapy to the prostate and lymph glands given in 5 visits, in men with high risk localised prostate cancer.

The purpose of the research is to test an advanced type of external beam radiotherapy called stereotactic body radiotherapy (also known as SBRT) in 1128 participants with high risk localised prostate cancer (that is, prostate cancer that has not spread beyond the prostate gland but is at high risk of growing quickly or spreading). Importantly, this treatment delivers a potentially curative dose of radiotherapy in only 5 treatments over two weeks. Half the participants in the trial will receive radiotherapy to the prostate, the other half will have radiotherapy to the prostate as well as the surrounding lymph nodes. The investigators will follow patients in the trial for at least three and half years to see which treatment is best. The investigators will be looking at whether it is safe to give this treatment by reviewing any side-effects that occur and also assessing whether giving SBRT to the lymph nodes as well as the prostate reduces the chance of prostate cancer returning.

The treatment will take place at NHS radiotherapy centres that are experienced in giving SBRT and radiotherapy to the pelvic nodes, and have been quality assured to deliver these treatments

Eligibility criteria: Inclusion Criteria:

1. Aged ≥ 18 years at randomisation
2. Histopathological confirmation of prostate adenocarcinoma with Gleason/ISUP grade group scoring within twelve months of randomisation (unless otherwise discussed with the CI or co-Clinical Leads)
3. Patients planned for 12-36 months androgen deprivation therapy
4. High risk localised prostate cancer as defined by

   * Gleason 8-10 (grade groups 4 and 5) and/or
   * Stage T3a/b or T4 and/or
   * PSA \> 20ng/ml (or \>10 ng/ml for patients on 5-alpha reductase inhibitors)
5. Multi-parametric MRI of the pelvis- to include at least one functional MRI sequence in addition to T2W imaging within twelve months of randomisation
6. Radiological staging to exclude metastatic disease, prior to starting ADT, with one of the following: PSMA PET-CT, fluciclovine/choline PET-CT, whole-body MRI, bone scan, CT of chest, abdomen and pelvis (imaging method as per local practice/standard of care).
7. WHO performance status 0-2
8. Ability of research subject to give written informed consent

Exclusion Criteria:

1. N1 or M1 disease
2. PSA \>50ng/ml (or \>25ng/ml for patients on 5-alpha reductase inhibitors), unless PET-CT imaging has been performed to confirm N0M0 disease
3. Previous active treatment for prostate cancer
4. Patients where SBRT is contraindicated: prior pelvic radiotherapy, inflammatory bowel disease, significant lower urinary tract symptoms N.B. where patient has repeated imaging showing bowel in close apposition to target volumes that would make pelvic radiotherapy highly unlikely to be deliverable should be excluded.
5. Contraindications to fiducial marker insertion, where used- including clotting disorders, or patients at high risk when stopping anticoagulation or antiplatelet medications
6. Bilateral hip prostheses or any other implants/hardware that would introduce substantial CT artefacts and would make pelvic node planning more difficult.
7. Patients who have had chemotherapy within 6 weeks of the start of radiotherapy.
8. Life expectancy \< 5 years

Primary outcomes:
measure: Time to biochemical or clinical failure
timeFrame: minimum of 3.5 years follow up post-randomisation
Secondary outcomes:
measure: Clinical reported acute toxicity
timeFrame: 12 weeks post-randomisation
measure: Clinical reported late toxicity
timeFrame: up to 5 years post-randomisation
measure: Metastatic relapse-free survival
timeFrame: up to 5 years post-randomisation
measure: Prostate cancer-specific survival
timeFrame: up to 5 years post-randomisation
measure: Overall survival
timeFrame: up to 5 years post-randomisation
measure: Patient Reported Outcome Measures
timeFrame: up to 5 years post-randomisation
measure: Adherence to radiotherapy protocol
timeFrame: after completion of treatment
Other outcomes:
Locations:
city: Cork
country: Ireland
facility: Bon Secours Radiotherapy Cork in partnership with UPMC Hillman Cancer Centre
city: Dublin
country: Ireland
facility: St Lukes Radiation Oncology Network
city: Limerick
country: Ireland
facility: Mid Western Radiation Oncology Centre
city: Auckland
country: New Zealand
facility: Auckland Hospital
city: Middlesbrough
country: United Kingdom
facility: James Cook University Hospital
state: South Tees
city: Worcester
country: United Kingdom
facility: Worcestershire Acute Hospitals Nhs Trust
state: Worcestershire
city: Belfast
country: United Kingdom
facility: Belfast City Hospital
city: Bristol
country: United Kingdom
facility: Bristol Haematology and Oncology Centre
city: Bury Saint Edmunds
country: United Kingdom
facility: West Suffolk NHS Foundation Trust
city: Cambridge
country: United Kingdom
facility: Addenbrookes Hospital
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Centre
city: Cheltenham
country: United Kingdom
facility: Gloucestershire Hospitals NHS Foundation Trust
city: Coventry
country: United Kingdom
facility: University Hospitals Coventry & Warwickshire NHS Trust
city: Derby
country: United Kingdom
facility: University Hospitals of Derby & Burton NHS Foundation Trust
city: Edmonton
country: United Kingdom
facility: North Middlesex University Hospital NHS Trust
city: Exeter
country: United Kingdom
facility: Royal Devon & Exeter
city: Guildford
country: United Kingdom
facility: Royal Surrey County Hospital NHS Foundation Trust
city: Hillingdon
country: United Kingdom
facility: Mount Vernon Cancer Centre
city: Ipswich
country: United Kingdom
facility: East Suffolk & North Essex NHS Foundation Trust
city: King's Lynn
country: United Kingdom
facility: Queen Elizabeth Hospital
city: Leeds
country: United Kingdom
facility: Leeds Teaching Hospitals NHS Trust
city: Leicester
country: United Kingdom
facility: University Hospitals of Leicester NHS Trust
city: Lincoln
country: United Kingdom
facility: United Linconshire Hospitals NHS Trust
city: London
country: United Kingdom
facility: Guy's and St Thomas' Hospital NHS Foundation Trust
city: London
country: United Kingdom
facility: Royal Free Hospital
city: London
country: United Kingdom
facility: St Bartholomew's Hospital
city: Maidstone
country: United Kingdom
facility: Maidstone and Tunbridge Wells NHS Trust
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
city: Newcastle upon Tyne
country: United Kingdom
facility: Freeman Hospital
city: Northampton
country: United Kingdom
facility: Northampton General Hospital NHS Trust
city: Norwich
country: United Kingdom
facility: Norfolk & Norwich University Hospitals NHS Foundation Trust
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospital NHS Trust
city: Oxford
country: United Kingdom
facility: Churchill Hospital
city: Plymouth
country: United Kingdom
facility: University Hospitals Plymouth NHS Trust
city: Portsmouth
country: United Kingdom
facility: Portsmouth Hospitals University NHS Trust
city: Sheffield
country: United Kingdom
facility: Sheffield Teaching Hospitals NHS Foundation Trust
city: Southend
country: United Kingdom
facility: Mid and South Essex NHS Foundation Trust
city: Stoke-on-Trent
country: United Kingdom
facility: University Hospital North Midlands NHS Trust
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital
city: Torquay
country: United Kingdom
facility: Torbay and South Devon NHS Foundation Trust
city: Truro
country: United Kingdom
facility: Royal Cornwall Hospital
city: Wirral
country: United Kingdom
facility: Clatterbridge Cancer Centre
Study officials:
References: