Clinical trial NCT04642027: PSMA-PET Guided Hypofractionated Salvage Prostate Bed Radiotherapy
Official title: PSMA-PET Guided Hypofractionated Salvage Prostate Bed Radiotherapy of Biochemical Failure After Radical Prostatectomy for Prostate Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Prostate Cancer
Cancer Recurrence
Keywords: PSMA-PET/CT
Salvage
Hypofractionation
Radiotherapy
Prostatectomy
Lead sponsor: University Medical Center Groningen
Sponsor class: OTHER
Collaborators: name: Dutch Cancer Society
First posted: 2020-11-24
Enrollment: 538
Sex: MALE
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 2 randomised arms
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: 5-year progression-free survival
timeFrame: 5 years
Secondary outcomes:
measure: Acute grade ≥ 2 gastrointestinal toxicity
timeFrame: Up to 3 months after completion of the RT
measure: Acute grade ≥ 2 genitourinary toxicities
timeFrame: Up to 3 months after completion of the RT
measure: Late grade ≥ 2 gastrointestinal toxicity
timeFrame: Up to 5 years after completion of the RT
measure: Late grade ≥ 2 genitourinary toxicity
timeFrame: Up to 5 years after completion of the RT
measure: Quality of life after radiation
timeFrame: Up to 5 years after completion of the RT
measure: Metastasis-free survival
timeFrame: 5 years
measure: Prostate cancer-specific mortality
timeFrame: 5 years
measure: Overall survival
timeFrame: 5 years
measure: Acute grade ≥ 2 gastrointestinal toxicity
timeFrame: Up to 3 months after completion of the RT
measure: Acute grade ≥ 2 genitourinary toxicities
timeFrame: Up to 3 months after completion of the RT
measure: Late grade ≥ 2 genitourinary toxicity
timeFrame: Up to 5 years after completion of the RT
measure: Quality of life after radiation
timeFrame: Up to 5 years after completion of the RT
Other outcomes:
Locations:
city: Leeuwarden
country: Netherlands
facility: Radiotherapy Institute Friesland
state: Friesland
city: Arnhem
country: Netherlands
facility: Radiotherapiegroep
state: Gelderland
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center
state: Gelderland
city: Maastricht
country: Netherlands
facility: Maastro Clinic
state: Limburg
city: Eindhoven
country: Netherlands
facility: Catharina-Hospital
state: Noord Brabant
city: Tilburg
country: Netherlands
facility: Verbeeten Institute
state: Noord-Brabant
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC (Location VUmc)
state: Noord-Holland
city: Deventer
country: Netherlands
facility: Radiotherapiegroep
state: Overijssel
city: Den Haag
country: Netherlands
facility: Haga Hospital
state: Zuid-Holland
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
state: Zuid-Holland
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
state: Zuid-Holland
city: Groningen
country: Netherlands
facility: UMCG
city: Vlissingen
country: Netherlands
facility: Zuidwest Radiotherapeutisch Instituut (ZRTI)
Study officials:
affiliation: UMCG
name: S. Aluwini, Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.