PSMA-PET Guided Hypofractionated Salvage Prostate Bed Radiotherapy (PERYTON)

PSMA-PET Guided Hypofractionated Salvage Prostate Bed Radiotherapy of Biochemical Failure After Radical Prostatectomy for Prostate Cancer

After radical prostatectomy approximately 15-40% of men develop a biochemical recurrence (BR) within 5 years.

The standard treatment of post-prostatectomy BR is salvage external beam radiation therapy (sEBRT). sEBRT can provide long-term disease control; with 5 year biochemical progression-free survival (bPFS) up to 60% and with most treatment failures in the first 2 years after sEBRT.

The main goal of this project is to investigate whether the oncologic outcome in patients with post-prostatectomy recurrent PCa can be improved, by increasing the biological effective radiation dose using a hypofractionated schedule of 20 x 3 = 60 Gy.

The study is designed as a prospective open phase III randomized multicenter trial. All patients with biochemical recurrence with a PSA < 1.0 ng/ml after radical prostatectomy for prostate cancer without evidence of lymph nodes or distance metastases will be included. PSA progression after prostatectomy defined as two consecutive rises with the final PSA > 0.1 ng/mL or three consecutive rises will be included.

All eligible patients will be randomized to one of the following two treatment arms:

Arm 1 = Conventional sEBRT to apply a total dose of 70 Gy in 35 daily fractions of 2 Gy during 7 weeks.

Arm 2 = Hypofractionated sEBRT to apply a total dose of 60 Gy in 20 fractions of 3 Gy during 4 weeks.

The primary endpoint will be the 5-year progression-free survival (PFS) after treatment.

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer; Cancer Recurrence
• Intervention / Treatment: Radiation: Conventional sEBRT; Radiation: Hypofractionated sEBRT

• Study Type: Interventional
• Enrollment (Estimated): 538
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: F. Staal, MD; Phone Number: 0031655257985; Email: f.h.e.staal@umcg.nl
• Study Contact Backup: Name: P. Veldhuijzen van Zanten; Phone Number: 0031503614659; Email: peryton@rt.umcg.nl

Study Locations

• Netherlands
  • Groningen, Netherlands, 9713GZ
    • Recruiting
    • UMCG
    • Contact: F.H.E. Staal, MD.; Email: PERYTON@rt.umcg.nl
  • Vlissingen, Netherlands
    • Recruiting
    • Zuidwest Radiotherapeutisch Instituut (ZRTI)
    • Contact: Inge Jacobs; Email: i.jacobs@zrti.nl
  • Friesland
    • Leeuwarden, Friesland, Netherlands
      • Recruiting
      • Radiotherapy Institute Friesland
      • Contact: M. de Jong, MD
  • Gelderland
    • Arnhem, Gelderland, Netherlands
      • Recruiting
      • Radiotherapiegroep
      • Contact: D. Haverkort, MD
    • Nijmegen, Gelderland, Netherlands
      • Recruiting
      • Radboud University Medical Center
      • Contact: R.J. Smeenk, MD, PhD
  • Limburg
    • Maastricht, Limburg, Netherlands
      • Recruiting
      • Maastro Clinic
      • Contact: B. Vanneste, MD
  • Noord Brabant
    • Eindhoven, Noord Brabant, Netherlands
      • Recruiting
      • Catharina-Hospital
      • Contact: T.C.G. Budiharto, MD, PhD
  • Noord-Brabant
    • Tilburg, Noord-Brabant, Netherlands
      • Recruiting
      • Verbeeten Institute
      • Contact: M.A.E. van de Sande, MD
  • Noord-Holland
    • Amsterdam, Noord-Holland, Netherlands
      • Not yet recruiting
      • Amsterdam UMC (Location VUmc)
      • Contact: J. van Moorselaar, Professor
  • Overijssel
    • Deventer, Overijssel, Netherlands
      • Recruiting
      • Radiotherapiegroep
      • Contact: D. Haverkort, MD
  • Zuid-Holland
    • Den Haag, Zuid-Holland, Netherlands
      • Not yet recruiting
      • Haga Hospital
      • Contact: B. Hollman, MD
    • Leiden, Zuid-Holland, Netherlands
      • Not yet recruiting
      • Leiden University Medical Center
      • Contact: S. Rademakers, MD, PhD
    • Rotterdam, Zuid-Holland, Netherlands
      • Not yet recruiting
      • Erasmus Medical Center
      • Contact: L. Incocci, Professor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with prostate adenocarcinoma treated with radical prostatectomy;
• Tumour stage pT2-4, R0-1, pN0, or cN0, cNx according to the UICC TNM 2009, only with Gleason score available;
• No lymph node or distant metastases. A recent PSMA-PET scan (< 60 days) without evidence of lymph node or distant metastases;
• PSA progression after prostatectomy defined as two consecutive rises with the final PSA > 0.1 ng/mL or 3 consecutive rises. The first value must be measured at least 6 weeks after radical prostatectomy;
• PSA at inclusion < 1.0 ng/mL;
• WHO performance status 0-2 at inclusion;
• Age at inclusion between 18 and 80 years;
• Written (signed and dated) informed consent prior to registration.

Exclusion Criteria:

• Prior pelvic irradiation, (chemo)hormonal therapy or orchiectomy;
• Previous or concurrent active invasive cancers other than superficial non-melanoma skin cancers;
• Patients with positive nodes or with distant metastases based on the surgical specimen of lymphadenectomy or the following minimum diagnostic workup: PSMA-PET/CT scan, 60 days prior to registration;
• Double-sided metallic hip prosthesis;
• Inability or unwillingness to understand the information on trial-related topics, to give informed consent or to fill out QoL questionnaires.

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: Conventional; Conventional sEBRT	Radiation: Conventional sEBRT; A total dose of70 Gy in 35 daily fractions of 2 Gy during 7 weeks; Other Names: Conventional salvage external beam radiation therapy
Experimental: Hypofractionation; Hypofractionated sEBRT	Radiation: Hypofractionated sEBRT; A total dose of 60 Gy in 20 daily fractions of 3 Gy during 4 weeks; Other Names: Hypofractionated salvage external beam radiation therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
5-year progression-free survival	Defined as biochemical progression, clinical progression, loco-regional or distant progression or start with hormonal therapy, whichever occurs first	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute grade ≥ 2 gastrointestinal toxicity	As assessed using physician-reported score: Common Terminology Criteria for adverse events version 5.0 (CTCAE-5) toxicity score with a scale of 1 - 4.	Up to 3 months after completion of the RT
Acute grade ≥ 2 genitourinary toxicities	As assessed using physician-reported score using questionnaires (CTCAE 5.0 toxicity score).	Up to 3 months after completion of the RT
Late grade ≥ 2 gastrointestinal toxicity	As assessed using physician-reported score (CTCAE 5.0 toxicity score).	Up to 5 years after completion of the RT
Late grade ≥ 2 genitourinary toxicity	Using physician-reported score (CTCAE 5.0 toxicity score).	Up to 5 years after completion of the RT
Quality of life after radiation	As assessed using patient-reported questionnaires: measurend with European platform of cancer research-QLQ C30	Up to 5 years after completion of the RT
Metastasis-free survival	Time from randomisation to the date of metastases reported by CT scan, MRI scan or PSMA-PET/CT during the follow up (date scan).	5 years
Prostate cancer-specific mortality	Prostate cancer-specific mortality.	5 years
Overall survival	Overall survival	5 years
Acute grade ≥ 2 gastrointestinal toxicity	Using patient-reported questionnaires (Radiation Therapy Oncology Group (RTOG) / European platform of cancer research (EORTC) toxicity questionnaires with grade 1 to 4).	Up to 3 months after completion of the RT
Acute grade ≥ 2 genitourinary toxicities	Using patient-reported questionnaires (Radiation Therapy Oncology Group (RTOG) / European platform of cancer research (EORTC) toxicity questionnaires with grade 1 to 4).	Up to 3 months after completion of the RT
Late grade ≥ 2 genitourinary toxicity	Using patient-reported questionnaires (Radiation Therapy Oncology Group (RTOG) / European platform of cancer research (EORTC) toxicity questionnaires with grade 1 to 4).	Up to 5 years after completion of the RT
Quality of life after radiation	As assessed using patient reported quatinnaires: European platform of cancer research-Quality of Life Questionnaire - Prostate Cancer Module (PR 25).	Up to 5 years after completion of the RT

Collaborators and Investigators

• Sponsor: University Medical Center Groningen
• Collaborators: Dutch Cancer Society
• Investigators: Principal Investigator: S. Aluwini, Dr., UMCG

Publications and helpful links

General Publications

• Staal FHE, Janssen J, Brouwer CL, Langendijk JA, Ng Wei Siang K, Schuit E, de Jong IJ, Verzijlbergen JF, Smeenk RJ, Aluwini S. Phase III randomised controlled trial on PSMA PET/CT guided hypofractionated salvage prostate bed radiotherapy of biochemical failure after radical prostatectomy for prostate cancer (PERYTON-trial): study protocol. BMC Cancer. 2022 Apr 15;22(1):416. doi: 10.1186/s12885-022-09493-5.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2020
• Primary Completion (Estimated): September 1, 2029
• Study Completion (Estimated): September 1, 2030

Study Registration Dates

• First Submitted: August 13, 2020
• First Submitted That Met QC Criteria: November 17, 2020
• First Posted (Actual): November 24, 2020

Study Record Updates

• Last Update Posted (Actual): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 26, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Radiotherapy; Prostatectomy; Hypofractionation; PSMA-PET/CT; Salvage
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Disease Attributes; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms; Recurrence
• Other Study ID Numbers: RT2020-01

Drug and device information, study documents

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