A Trial of 5 Fraction Prostate SBRT Versus 5 Fraction Prostate and Pelvic Nodal SBRT (PACE-NODES)

PACE-NODES. A Phase III Randomised Trial of 5 Fraction Prostate SBRT Versus 5 Fraction Prostate and Pelvic Nodal SBRT

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.

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer
• Intervention / Treatment: Radiation: SBRT

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 536 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

• Study Type: Interventional
• Enrollment (Anticipated): 536
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: PACE-NODES Trial Manager; Phone Number: 02087224000; Email: pace-nodes-icrctsu@icr.ac.uk
• Study Contact Backup: Name: PACE-NODES CTPM; Phone Number: 02087224000; Email: pace-nodes-icrctsu@icr.ac.uk

Study Locations

• United Kingdom
  • South Tees
    • Middlesbrough, South Tees, United Kingdom
      • Recruiting
      • James Cook University Hospital
      • Contact: Darren Leaning

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: P-SBRT; Participants allocated P-SBRT will receive 36.25Gy in 5 fractions to the prostate and seminal vesicles on alternate days (40Gy to prostate CTV).	Radiation: SBRT; Stereotactic Body Radiotherapy; Other Names: SABR
Experimental: PPN-SBRT; Participants allocated PPN-SBRT will receive 36.25Gy in 5 fractions to the prostate and seminal vesicles on alternate days (40Gy to prostate clinical target volume (CTV)) and 25Gy in 5 fractions to pelvic nodes on alternate days.	Radiation: SBRT; Stereotactic Body Radiotherapy; Other Names: SABR

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to biochemical or clinical failure	Time to biochemical or clinical failure as defined by time from randomisation to the first progression event (either biochemical failure, local recurrence, lymph node/pelvic recurrence, distant metastases, recommencement of androgen deprivation therapy or death due to prostate cancer).	minimum of 3.5 years follow up post-randomisation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical reported acute toxicity	Clinical reported acute and late toxicity using CTCAE version 5.0 and RTOG criteria. Focus will be given to GU and GI Grade 2 or higher (G2+) toxicities	12 weeks post-randomisation
Clinical reported late toxicity	Clinical reported acute and late toxicity using CTCAE version 5.0 and RTOG criteria. Focus will be given to GU and GI Grade 2 or higher (G2+) toxicities	up to 5 years post-randomisation
Metastatic relapse-free survival	Time from randomisation to distant metastases or death from prostate cancer	up to 5 years post-randomisation
Prostate cancer-specific survival	Time from randomisation to death due to prostate cancer	up to 5 years post-randomisation
Overall survival	Time from randomisation to death from any cause	up to 5 years post-randomisation
Patient Reported Outcome Measures	Quality of life will be evaluated using combined data from the following questionnaires. IPSS questionnaire: a validated diagnostic tool used to assess urinary & bowel incontinence. IIEF-5: validated diagnostic tool for erectile dysfunction. EPIC questionnaire: to assess typical symptoms after radiotherapy in prostate cancer patients. EQ-5D: a commonly used generic questionnaire to measure health-related QoL used to asess mobility, self-care, usual activities, pain/discomfort, anxiety/depression & the subject's perceptions of their own current overall health. A QoL analysis plan will be developed in consultation with the TMG with key endpoints for each questionnaire. Standard algorithms will be used to derive scores and handle missing data. Changes from baseline at each time point will be compared within groups as well as between treatment groups (by means of ordinal logistic regressions or ANCOVA models). Analyses to account for the longitudinal nature of the data may be used.	up to 5 years post-randomisation
Adherence to radiotherapy protocol	Qualitative analysis of adherence to pre-specified radiotherapy dose constraints with radiotherapy quality assurance to demonstrate feasibility in a muliticentre setting.	after completion of treatment

Collaborators and Investigators

• Sponsor: Institute of Cancer Research, United Kingdom
• Collaborators: Prostate Cancer UK

Study record dates

Study Major Dates

• Study Start (Actual): September 9, 2022
• Primary Completion (Anticipated): June 1, 2028
• Study Completion (Anticipated): June 1, 2030

Study Registration Dates

• First Submitted: March 7, 2022
• First Submitted That Met QC Criteria: November 10, 2022
• First Posted (Actual): November 14, 2022

Study Record Updates

• Last Update Posted (Actual): November 14, 2022
• Last Update Submitted That Met QC Criteria: November 10, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms
• Other Study ID Numbers: CCR5545; Prostate Cancer UK (Other Grant/Funding Number: MA-CT20-005)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No