Prostate Advances in Comparative Evidence (PACE)

• ClinicalTrials.gov Identifier: NCT01584258
• Recruitment Status: Recruiting
• First Posted: April 24, 2012
• Last Update Posted: April 27, 2015
• Sponsor: Royal Marsden NHS Foundation Trust
• Collaborator: The Institute of Cancer Research, Sutton, Surrey, UK
• Information provided by (Responsible Party): Royal Marsden NHS Foundation Trust

Tracking Information

• First Submitted Date: April 22, 2012
• First Posted Date: April 24, 2012
• Last Update Posted Date: April 27, 2015
• Study Start Date: April 2012
• Estimated Primary Completion Date: September 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 7, 2015)

Biochemical progression-free survival [ Time Frame: 5 years (primary timepoint) ]

Biochemical progression is defined as follows: For conventional radiation and SBRT arms- Phoenix definition; For surgical arm- PSA > 0.2 ng/mL.

Original Primary Outcome Measures (submitted: April 22, 2012)

Biochemical disease-free survival [ Time Frame: 5 years (primary timepoint) ]

Biochemical progression is defined as follows: For conventional radiation and radiosurgery arms: Serum PSA of at least 2 ng/mL greater than the post-radiotherapy nadir (lowest PSA to date)(Phoenix definition); for surgical arm: PSA > 0.2 ng/mL. For either arm, a recommencement of androgen deprivation also counts as biochemical failure.

Current Secondary Outcome Measures (submitted: April 7, 2015)

• Toxicity assessment for surgical and SBRT arm [ Time Frame: 10 years ]
  CTCAEv4.03 and RTOG for acute and late toxicity. Clavien scale used to assess acute post surgical complications for surgical patients only.
• Toxicity assessment for conventionally fractionated and SBRT arm [ Time Frame: 10 years ]
  CTCAEv4.03 and RTOG acute and late toxicity scoring. During the treatment period of conventional radiation therapy and SBRT, treatment associated toxicities are assessed using RTOG scoring only.
• Patient reported outcomes and quality of life assessment for all treatment arms [ Time Frame: 10 years ]
  International Index of Erectile Function-5 (IIEF-5), International Prostate Symptom Score (IPSS), Vaizey score (UK and US patients only) Expanded Prostate Index Composite-26 (EPIC-26) and PR-25 (PR-25 is optional)
• Disease-specific and overall survival [ Time Frame: 10 years ]
  Disease-specific and overall survival
• Progression-free survival [ Time Frame: 10 years ]
  Radiographic, clinical or biochemical evidence of local or distant failure
• Commencement of androgen deprivation therapy [ Time Frame: 10 years ]
  LHRH analogues, anti-androgens, orchidectomy

Original Secondary Outcome Measures (submitted: April 22, 2012)

• Cause-specific and overall survival [ Time Frame: 10 years ]
  Cause-specific survival will include deaths from prostate cancer only. Overall survival will include deaths from any cause.
• Progression-free survival [ Time Frame: 10 years ]
  Radiographic or clinical evidence of local, regional or distant failure.
• Toxicities associated with surgery, radiotherapy and radiosurgery [ Time Frame: 10 years ]
  Assessed by CTCAE version 4
• Quality of Life [ Time Frame: 10 years ]
  Using EORTC Quality of Life Questionnaire PR-25

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Prostate Advances in Comparative Evidence
• Official Title: International Randomised Study of Laparoscopic Prostatectomy vs Stereotactic Body Radiotherapy (SBRT) and Conventionally Fractionated Radiotherapy vs SBRT for Early Stage Organ-Confined Prostate Cancer
• Brief Summary: This study is an international multicentre randomised study of organ confined low and intermediate risk prostate cancer and is composed of two parallel randomisation schemes based on applicability of surgery as a treatment for the patient. Patients for whom surgery is a consideration are randomised to either laparoscopic prostatectomy or prostate SBRT. Patients for whom surgery is not a consideration are randomised to either conventionally fractionated radiation therapy or prostate SBRT. Efficacy, toxicity and quality of life outcomes will be compared across the pairs in each randomisation.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Prostate Cancer

Intervention

• Procedure: Laproscopic Prostatectomy
• Radiation: Conventionally Fractionated Prostate Radiotherapy
  Conventional fractionation delivered to a dose of 78 Gy in 2 Gy fractions.
• Radiation: Prostate SBRT
  Prostate SBRT delivered to a dose of 36.25 Gy in 5 fractions.

Study Arms

• Active Comparator: Laparoscopic Prostatectomy vs prostate SBRT
  Patients for whom surgery is considered will be randomised to laparoscopic prostatectomy or prostate SBRT delivered with 36.25 Gy in 5 fractions.
  Interventions:

  • Procedure: Laproscopic Prostatectomy
  • Radiation: Prostate SBRT
• Active Comparator: Conventionally Fractionated RT vs Prostate SBRT
  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 2 Gy fractions or SBRT delivered with 36.25 Gy in 5 fractions.
  Interventions:

  • Radiation: Conventionally Fractionated Prostate Radiotherapy
  • Radiation: Prostate SBRT

• Publications *: 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.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 20, 2015): 1716
• Original Estimated Enrollment (submitted: April 22, 2012): 1036
• Estimated Study Completion Date: September 2026
• Estimated Primary Completion Date: September 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria: All of the following criteria are mandatory for inclusion:

• Histological confirmation of prostate adenocarcinoma with a minimum of 10 biopsy cores taken within 18 months of randomisation.
• Gleason score ≤ 3+4
• Men aged ≥18
• Clinical and MRI stage T1c -T2c, N0-X, M0-X (TNM 6th Edition [72], See Appendix 1)
• PSA ≤ 20 ng/ml
• Pre-enrollment PSA must be completed within 60 days of randomisation

• Patients belonging in one of the following risk groups according to the National Comprehensive Cancer Network (www.nccn.org):

  • Low risk: Clinical stage T1-T2a and Gleason ≤ 6 and PSA < 10 ng/ml, or
  • Intermediate risk includes any one of the following:
  • Clinical stage T2b orT2c
  • PSA 10-20 ng/ml or
  • Gleason 3+4
• WHO performance status 0 - 2
• Prostate volume ≤ 90 cc measured within 6 months of randomisation (height*width*length *π/6)
• Ability of the research subject to understand and the willingness to sign a written informed consent document

Exclusion criteria: One of the following criteria is sufficient for exclusion:

• Clinical stage T3 or greater
• Gleason score ≥ 4 + 3
• High risk disease defined by National Comprehensive Cancer Network (www.nccn.org)
• 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 LHRH agonists and antagonists and anti-androgens)
• Any prior active treatment for prostate cancer. 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 artifacts
• Medical conditions likely to make radiotherapy inadvisable eg inflammatory bowel disease, significant urinary symptoms
• Anticoagulation with warfarin/ bleeding tendency making fiducial placement or surgery unsafe in the opinion of the clinician (see section 11, Treatment).
• Participation in another concurrent treatment protocol for prostate cancer

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Hassan Nawrozzadeh; +44 208 722 4467; Pace-icrctsu@icr.ac.uk

Contact: Clare Cruickshank; +44 208 722 4467; Pace-icrctsu@icr.ac.uk

• Listed Location Countries: United Kingdom

Administrative Information

• NCT Number: NCT01584258
• Other Study ID Numbers: ACCP003
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Royal Marsden NHS Foundation Trust
• Study Sponsor: Royal Marsden NHS Foundation Trust
• Collaborators: The Institute of Cancer Research, Sutton, Surrey, UK

Investigators

• Study Director: Nicholas van As, MD; Royal Marsden NHS Foundation Trust, London, United Kingdom
• Principal Investigator: Peter Ostler, MD; Mount Vernon Cancer Centre, United Kingdom

• PRS Account: Royal Marsden NHS Foundation Trust
• Verification Date: April 2015