Prostatic NeoplasmsPhase 3ESCALATE-RTNCT07782112
Best Salvage Treatment for High-risk Relapsing Prostate Cancer (PEACE-9 - ESCALATE-RT)
A Phase 3 study testing Radiotherapy for MDT ± WPRT, Androgen Deprivation Therapy (ADT) and Enzalutamide in people with Prostatic Neoplasms and Biochemical Recurrence, run by Ente Ospedaliero Cantonale, Bellinzona at 19 sites in 3 countries.
Trial summary
The goal of this clinical trial is to learn if adding metastasis-directed radiotherapy with or without pelvic salvage radiotherapy, to intermittent prostate cancer drugs (intensified hormone therapy) can delay the need to restart these drugs in men with oligometastactic prostate cancer recurrence. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostatic Neoplasms, Biochemical Recurrence, Oligometastatic Prostate Cancer
- What is being tested?
- Radiotherapy for MDT ± WPRT, Androgen Deprivation Therapy (ADT) and Enzalutamide
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 140 participants
- Where
- 19 sitesin 3 countries
- Study dates
- Nov 2026to Jul 2030
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically proven initial diagnosis of adenocarcinoma of the prostate
- Rising PSA after local therapy as defined by PSA ≥ 0.2 ng/mL after RP +/- adjuvant/salvage prostate bed RT and at least 2 ng/mL above nadir for primary RT, with a PSADT ≤ 9 months
- Serum Testosterone ≥ 150 ng/dl (6.9343 nM/L)
- On PSMA PET/CT restaging presence of: 1 to 5 distant metastases that are amenable to MDT ± N1 patients (no limit in the number of nodes)
- ECOG performance status 0 - 2
- Age > or =18 years
- Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
- Before patient registration/randomization, written informed consent must be given according to ICH/GCP, and national/local regulations
Who cannot join
- More than 5 distant PSMA positive metastases and/or brain or leptomeningeal metastases.
- Prostate recurrence (positive PSMA disease) after primary prostate irradiation
- Prostate bed recurrence (positive PSMA disease) after salvage/adjuvant irradiation
- Pelvic nodal recurrence (positive PSMA disease) after primary WPRT irradiation
- Contraindications to pelvic RT and/or MDT
- Prior evidence of distant metastatic disease
Show all 11Show fewer
- Contraindications to ADT
- Contraindication for treatment with enzalutamide
- Prior hormonal therapy (Neoadjuvant/adjuvant therapy to treat PCa ≤ 36 months in duration and ≥ 9 months before randomization is allowed)
- Previous treatment with cytotoxic agent for PCa
- Any active malignancies (i.e., progressing or requiring any treatment in the previous 36 months) other than prostate cancer (except non-muscle invasive bladder cancer; non-melanomatous skin cancer or a malignancy that is considered cured with minimal risk of recurrence
Trial locations and contacts
19 sites in 3 countries. Contact the study team or a site near you to ask about taking part.
Tatiana Terrot contact
19 sites in 3 countries
Belgium7 sites
AZorg Aalst
Aalst
Mark De Ridder, MD
Iridium Netwerk
Antwerp
Piet Ost, MD, PhD
AZ Sint-Jan
Bruges
Sarah Roels, MD
Institut Bordet - HUB Brussel
Brussels
Dirk Van Gestel, MD
Jessa ziekenhuis
Hasselt
Philippe Bulens, MD
AZ Groeninge
Kortrijk
Aurélie De Bruycker, MD
AZ Sint-Maarten Mechelen
Mechelen
Cédric Draulans, MD
Switzerland7 sites
KSA
Aarau
Stephanie Thoma, MD, stephanie.thoma@ksa.ch
IOSI-EOC
Bellinzona, 6500
Thomas Zilli, MD, + 41 918118675, thomas.zilli@eoc.ch
Inselspital
Bern
Mohamed Shelan, MD, Mohamed.Shelan@insel.ch
KSGR
Chur
Efstratios Karagiannis, MD, PhD, Efstratios.Karagiannis@ksgr.ch
Spital Thurgau
Münsterlingen
Michael Mayinger, MD, michael.mayinger@team-radiologie.ch
KSW
Winterthur
Daniel Zwahlen, MD, daniel.zwahlen@ksw.ch
USZ
Zurich
Matthias Guckenberger, MD, Matthias.Guckenberger@usz.ch
France5 sites
Institut Bergonié
Bordeaux
Vérane Achard, MD, PhD
Centre Oscar Lambret
Lille
David Pasquier, MD, PhD
CHU de Saint-Etienne
Saint-Etienne
Nicolas Vial, MD, nicolas.vial@chu-st-etienne.fr
nicolas.vial@chu-st-etienne.fr
Institut de Cancérologie de l'Ouest
Saint-Herblain
Stéphane Supiot, MD, PhD
Institut Gustave Roussy
Villejuif
Pierre Blanchard, MD, PhD
About this study
Official title: PEACE-9 - ESCALATE-RT: A Phase III Randomized Study in Patients With High-risk PSA Relapse After Local Therapy Treated With Enzalutamide Plus Androgen Deprivation Therapy and Comparing MDT ± Pelvic Radiotherapy Versus no Further Treatment
The goal of this clinical trial is to learn if adding metastasis-directed radiotherapy with or without pelvic salvage radiotherapy, to intermittent prostate cancer drugs (intensified hormone therapy) can delay the need to restart these drugs in men with oligometastactic prostate cancer recurrence.
In practice, this study is open to men whose PSA level (a blood marker of cancer activity) is rising as defined by biochemical recurrence, and who have 1 to 5 areas of cancer spread (1 to 5 metastases defining oligometastatic status) found on a specialized scan (PSMA PET/CT).
Read more
Since intensified hormone therapy, including androgen deprivation therapy combined with a next-generation hormone therapy, represents the standard treatment strategy for these patients, researchers want to find out if adding radiation therapy can help patients to spend more time off cancer drugs while keeping their cancer under control.
The main questions this trial aims to answer are:
- Does adding radiation therapy to each metastases with or without pelvic area, lengthen the time before participants need to restart drug treatment?
- Does adding radiation therapy increase the number of participants whose PSA drops to a very low level (0.2 ng/mL or lower)?
- Does adding radiation therapy affect participants' quality of life?
Researchers will randomly assign participants (chosen by chance) to receive either enzalutamide (next-generation hormone therapy) plus androgen-deprivation therapy (first-generation hormone therapy ) alone, or the same association of these drugs combined with radiation therapy aimed at each metastases with or without pelvic area.
This comparison will show whether adding radiation therapy helps participants reach a deeper PSA response and go longer without needing cancer drugs.
Participants will:
- Take enzalutamide and androgen-deprivation therapy for 9 months
- Have an equal chance of also receiving radiation therapy to each metastases with or without pelvic area
- Stop drug treatment after 9 months if their PSA drops below 0.2 ng/mL, a level showing the cancer is well controlled
- Restart drug treatment if their PSA rises again during the treatment-free period
- Have regular blood tests and clinic visits to check their PSA, testosterone, and overall health
- Complete short quality-of-life questionnaires during the study
- Take part in a study conducted at several hospitals in Switzerland, Belgium, and France.
- Being tested
- Radiotherapy for MDT ± WPRT, Androgen Deprivation Therapy (ADT), Enzalutamide
- Keywords
- High-risk PSA relapse, Oligometastatic recurrence, Salvage treatment, Metastasis-directed therapy, Pelvic radiotherapy, Androgen Deprivation Therapy, Enzalutamide
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Radiotherapy for MDT ± WPRTRadiation
Participants receive metastasis-directed therapy (MDT) alone or combined with prostate-bed radiotherapy (PB-RT) and/or whole pelvic radiotherapy (WPRT), as follows (radiotherapy is tailored to each participant's prior curative treatment for prostate cancer, to avoid re-irradiating previously treated volumes) :
- Prior radical prostatectomy (RP) alone: MDT plus PB-RT, with or without WPRT. WPRT is mandatory for pelvic nodal involvement (N1) and recommended for node-negative (N0) participants.
- Prior RP plus PB-RT: MDT, with or without WPRT. WPRT is mandatory for N1 and recommended for N0 participants.
- Prior RP plus PB-RT plus WPRT: MDT alone.
- Prior definitive prostate radiotherapy (no prostatectomy): MDT, with or without WPRT. WPRT is mandatory for N1 and recommended for N0 participants.
Androgen Deprivation Therapy (ADT)Drug
- All arms should receive ADT for a duration of at least 36 weeks.
- The prescription of ADT in both treatment arms will be in accordance with standard practice for the indication, the chosen molecules, and the selected doses.
- ADT should be suspended at the end of week 36, if PSA < 0.2 ng/mL at week 36. In the off-period, ADT will be restarted with a rise of PSA to ≥ 5 ng/mL after primary RT or to ≥ 2 ng/mL after RP ± postoperative RT. For patients in the off-period with rising PSA < 5 ng/mL after primary RT or < 2ng/mL after RP
- postoperative RT, the decision to restart treatment is led to each investigator.
- ADT should be continued until progression at the end of week 36, if PSA ≥ 0.2 ng/mL at week 36.
EnzalutamideDrug
- All arms should receive enzalutamide 160mg daily for a duration of at least 36 weeks.
- Enzalutamide should be suspended at the end of week 36, if PSA < 0.2 ng/mL at week 36. In the off-period, Enzalutamide will be restarted with a rise of PSA to ≥ 5 ng/mL after primary RT or to ≥ 2 ng/mL after RP ± postoperative RT. For patients in the off-period with rising PSA < 5 ng/mL after primary RT or < 2ng/mL after RP ± postoperative RT, the decision to restart treatment is led to each investigator.
- Enzalutamide should be continued until progression at the end of week 36, if PSA ≥ 0.2 ng/mL at week 36.
| Study group | Role | What they receive |
|---|---|---|
| ADT plus Enzalutamide | Active comparator | Enzalutamide 160 mg daily + androgen deprivation therapy for 9 months, suspended if PSA < 0.2 ng/mL, followed by PSA monitoring until progression Receives: Drug: Androgen Deprivation Therapy (ADT); Drug: Enzalutamide |
| ADT plus Enzalutamide plus Radiotherapy (MDT +/- WPRT) | Experimental | Enzalutamide 160 mg daily + androgen deprivation therapy for 9 months, suspended if PSA < 0.2 ng/mL, followed by PSA monitoring until progression + Radiotherapy for MDT ± WPRT Receives: Radiation: Radiotherapy for MDT ± WPRT; Drug: Androgen Deprivation Therapy (ADT); Drug: Enzalutamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to first re-initiation of treatment
- Time to first re-initiation of treatment calculated from randomization to the occurrence of one of the following events:
- PSA ≥ 0.2 ng/mL at week 36 (treatment is continued until progression),
- For patients in the off-period, a rise of PSA to ≥ 5 ng/mL after primary RT or to ≥ 2 ng/mL after RP ± postoperative RT (treatment is restarted as per EMBARK criteria)
- For patients in the off-period with rising PSA < 5 ng/mL after primary RT or <2ng/mL after RP ± postoperative RT, the investigator decision to start same or new treatment.
Death in the absence of progressive disease will be considered as a competing risk for this endpoint.
Measured: From the start of Androgen Deprivation Therapy plus Enzalutamide to 5 years after this date
Secondary outcomes (11)
Time to PSA progression
Time to PSA progression: defined by the time from the day of PSA nadir and the day when the PSA increase of ≥ 25% and an absolute increase of ≥ 2 ng/mL above the nadir.
Measured: From the start of Androgen Deprivation Therapy plus Enzalutamide to 5 years after this date
PFS (Progression-Free Survival)
PFS: defined as the time from randomization to the first progression or death (progression being defined by the appearance of a new recurrence (any N1 or M1) as suggested by PET-CT, or symptoms related to progressive prostate cancer, or death due to any cause).
Measured: From the start of Androgen Deprivation Therapy plus Enzalutamide to 5 years after this date
MFS (Metastasis-Free Survival)
MFS: defined as time between randomization and the appearance of a new metastatic recurrence (any M1) as suggested by PET-CT, or death due to any cause.
Measured: From the start of Androgen Deprivation Therapy plus Enzalutamide to 5 years after this date
OS (Overall Survival)
OS: defined as the time from randomization to death to any cause.
Measured: From the start of Androgen Deprivation Therapy plus Enzalutamide to 5 years after this date
PSA response
PSA response: defined by a PSA < 0.2 ng/ml at 9 months.
Measured: From the start of Androgen Deprivation Therapy plus Enzalutamide to 5 years after this date
Pattern of progression
Local/regional/distant recurrence will be analyzed:
- A local recurrence is defined as the appearance of evidence of a recurrence on imaging inside a PTV_M volume or the PTV_PB volume or the PTV_LNN.
- A regional nodal recurrence is defined as the appearance of evidence of a lymphadenopathy in the pelvis but outside the PTV_LNN volume, in a patient without the diagnosis of hematologic/lymphatic disorder associated with lymphadenopathy or if there is histopathological evidence.
- Distant recurrence is defined as the appearance of evidence of a lymphadenopathy outside the PTV_LNN and outside all the PTV_M (for lymph nodes previously treated as metastasis), or distant metastases (M1b, M1c) outside all the PTV_M.
Measured: From the start of Androgen Deprivation Therapy plus Enzalutamide to 5 years after this date
Time to castration-resistant disease
Time to castration-resistant disease is defined as the time from trial randomization until castration-resistant status, defined as a castrate serum testosterone level below 50 ng/dL (1.7 nmol/L) plus either biochemical progression or radiological progression. Biochemical progression is defined as three consecutive rises in PSA at least 1 week apart, resulting in two 50% increases over the nadir, with a PSA level above 2 ng/mL. Radiological progression is defined as the appearance of two or more new bone lesions on bone scan, or enlargement of a soft tissue lesion using RECIST (Response Evaluation Criteria in Solid Tumours). Symptomatic progression alone is not sufficient to diagnose castration-resistant prostate cancer (CRPC).
Measured: From the start of Androgen Deprivation Therapy plus Enzalutamide to 5 years after this date
Adverse events
Adverse events: acute (during the first 3 months after the end of MDT ± WPRT and late (3 months after the end of MDT ± WPRT).
Measured: From the start of Androgen Deprivation Therapy plus Enzalutamide to 5 years after this date
Quality of life (QoL) - EORTC QLQ-C30
EORTC Quality of Life Questionnaire Core 30 (QLQ-C30), version 3, a 30-item questionnaire. Items are rated on a 4-point scale (1 = "Not at all" to 4 = "Very much"), except the two global health status/QoL items, rated on a 7-point scale (1 = "Very poor" to 7 = "Excellent"). Raw scores are linearly transformed to a 0-100 scale. Higher scores indicate better functioning/quality of life on the functional and global health scales, and greater symptom burden on the symptom scales.
Measured: From the start of Androgen Deprivation Therapy plus Enzalutamide to 5 years after this date
Quality of Life - EORTC QLQ-PR25
EORTC Quality of Life Questionnaire Prostate Cancer Module (QLQ-PR25), a 25-item module supplementing the QLQ-C30. Items are rated on a 4-point scale (1 = "Not at all" to 4 = "Very much"). Raw scores are linearly transformed to a 0-100 scale. Higher scores indicate greater symptom burden, except for sexual activity/functioning scales, where higher scores indicate better functioning.
Measured: From the start of Androgen Deprivation Therapy plus Enzalutamide to 5 years after this date
Quality of Life - EORTC IL-249
A customised 22-item list from the EORTC IL-249, assessing general symptoms, weight-related issues, and sexual quality of life. Items are rated on a 4-point scale (1 = "Not at all" to 4 = "Very much"). Raw scores are linearly transformed to a 0-100 scale; higher scores indicate a greater burden of symptoms or issues.
Measured: From the start of Androgen Deprivation Therapy plus Enzalutamide to 5 years after this date
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Aug 2026
- Study startNov 2026 (estimated)
- Primary completionJul 2030 (estimated)
- Study completionJul 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Prostatic NeoplasmsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Superiority design
- Masking
- None (open label)
- Enrolment
- 140 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ente Ospedaliero Cantonale, Bellinzona
- Sponsor type
- University, hospital or other
- Collaborators
- Clinical Trial Unit Ente Ospedaliero Cantonale
- Responsible party
- Principal investigator, Thomas Zilli, Ente Ospedaliero Cantonale, Bellinzona
- Investigators
- Thomas Zilli, MD, Principal investigator, IOSI-EOCBertrand Tombal, MD, PhD, Study chair, Urology, Cliniques Universitaires Saint Luc, Bruxelles, BelgiumPiet Ost, MD, PhD, Study chair, Department of Human Structure and Repair, Ghent University, Ghent, Belgium; Department of Radiation Oncology, Iridium Network, Wilrijk, BelgiumSilke Gillessen, MD, Study chair, IOSI-EOCPiet Dirix, MD, PhD, Study chair, Department of Radiation Oncology, Iridium Network, Wilrijk, BelgiumSalvatore Cozzi, MD, Study chair, IOSI-EOCNicolas Vial, MD, Study chair, University Hospital of Saint-Etienne
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07782112
- Sponsor's protocol ID
- PEACE-9 - ESCALATE-RT
- Acronym
- ESCALATE-RT
- Status last verified
- Aug 2026
- First submitted
- 19 Aug 2026
- Last updated
- 24 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Nguyen PL, Kollmeier MA, Rathkopf DE, Hoffman KE, Zurita AJ, Spratt DE, Dess RT, Liauw SL, Szmulewitz RZ, Einstein DJ, Bubley GJ, Yu JB, An Y, Wong AC, Feng FY, McKay RR, Rose BS, Shin KY, Kibel AS, Taplin ME. FORMULA-509: A Multicenter Randomized Trial of Postprostatectomy Salvage Radiotherapy and 6 months of a GNRH Agonist with Either Bicalutamide or Abiraterone Acetate plus Prednisone and Apalutamide. Eur Urol. 2026 Feb 10:S0302-2838(25)04854-7. doi: 10.1016/j.eururo.2025.12.001. Online ahead of print.
PubMed 41672869Tang C, Sherry AD, Hwang H, Farris DP, Francolini G, Di Cataldo V, Livi L, Tran P, Corn PG, Aparicio A, Simontacchi G, Kiess AP, Wang JH, Fonteyne V, Bultijnck R, Phillips R, Deek MP, Olson R, Harrow S, Marvaso G, Lorubbio C, Jereczek-Fossa BA, Ludmir EB, Blanchard P, Warner A, Sun R, Palma DA, Ost P. Metastasis-directed therapy and standard of care versus standard of care for oligometastatic prostate cancer (WOLVERINE): a systematic review and individual patient data meta-analysis from the X-MET collaboration. Lancet Oncol. 2026 Feb;27(2):181-190. doi: 10.1016/S1470-2045(25)00658-8.
PubMed 41643695Tang C, Sherry AD, Haymaker C, Bathala T, Liu S, Fellman B, Cohen L, Aparicio A, Zurita AJ, Reuben A, Marmonti E, Chun SG, Reddy JP, Ghia A, McGuire S, Efstathiou E, Wang J, Wang J, Pilie P, Kovitz C, Du W, Simiele SJ, Kumar R, Borghero Y, Shi Z, Chapin B, Gomez D, Wistuba I, Corn PG. Addition of Metastasis-Directed Therapy to Intermittent Hormone Therapy for Oligometastatic Prostate Cancer: The EXTEND Phase 2 Randomized Clinical Trial. JAMA Oncol. 2023 Jun 1;9(6):825-834. doi: 10.1001/jamaoncol.2023.0161.
PubMed 37022702Holzgreve A, Armstrong WR, Clark KJ, Benz MR, Smith CP, Djaileb L, Gafita A, Thin P, Nickols NG, Kishan AU, Rettig MB, Reiter RE, Czernin J, Calais J. PSMA-PET/CT Findings in Patients With High-Risk Biochemically Recurrent Prostate Cancer With No Metastatic Disease by Conventional Imaging. JAMA Netw Open. 2025 Jan 2;8(1):e2452971. doi: 10.1001/jamanetworkopen.2024.52971.
PubMed 39752157Bukavina L, Luckenbaugh AN, Hofman MS, Hope T, Kamran SC, Murphy DG, Yamoah K, Ost P. Incorporating Prostate-specific Membrane Antigen Positron Emission Tomography in Management Decisions for Men with Newly Diagnosed or Biochemically Recurrent Prostate Cancer. Eur Urol. 2023 Jun;83(6):521-533. doi: 10.1016/j.eururo.2022.10.024. Epub 2022 Nov 18.
PubMed 36404204Shore ND, Luz MA, De Giorgi U, Gleave M, Gotto GT, Pieczonka CM, Haas GP, Kim CS, Ramirez-Backhaus M, Rannikko A, Kalac M, Sridharan S, Rosales M, Tang Y, Tutrone RF Jr, Venugopal B, Villers A, Woo HH, Wang F, Freedland SJ. Improved Survival with Enzalutamide in Biochemically Recurrent Prostate Cancer. N Engl J Med. 2026 Feb 5;394(6):563-575. doi: 10.1056/NEJMoa2510310. Epub 2025 Oct 19.
PubMed 41124201Crook JM, O'Callaghan CJ, Duncan G, Dearnaley DP, Higano CS, Horwitz EM, Frymire E, Malone S, Chin J, Nabid A, Warde P, Corbett T, Angyalfi S, Goldenberg SL, Gospodarowicz MK, Saad F, Logue JP, Hall E, Schellhammer PF, Ding K, Klotz L. Intermittent androgen suppression for rising PSA level after radiotherapy. N Engl J Med. 2012 Sep 6;367(10):895-903. doi: 10.1056/NEJMoa1201546.
PubMed 22931259
Study at a glance
From the registry record, last updated by the sponsor on 24 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PEACE-9 - ESCALATE-RT: A Phase III Randomized Study in Patients With High-risk PSA Relapse After Local Therapy Treated With Enzalutamide Plus Androgen Deprivation Therapy and Comparing MDT ± Pelvic Radiotherapy Versus no Further Treatment
- ClinicalTrials.gov ID
- NCT07782112
- Acronym / sponsor ID
- ESCALATE-RT / PEACE-9 - ESCALATE-RT
- Keywords
- High-risk PSA relapse, Oligometastatic recurrence, Salvage treatment, Metastasis-directed therapy, Pelvic radiotherapy, Androgen Deprivation Therapy, Enzalutamide
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 140 participants (estimated)
- Lead sponsor
- Ente Ospedaliero Cantonale, BellinzonaUniversity, hospital or other
- Collaborators
- Clinical Trial Unit Ente Ospedaliero Cantonale
- Study start
- Nov 2026 (estimated)
- Primary completion
- Jul 2030 (estimated)
- Study completion
- Jul 2030 (estimated)
- First posted
- 24 Aug 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical trial is to learn if adding metastasis-directed radiotherapy with or without pelvic salvage radiotherapy, to intermittent prostate cancer drugs (intensified hormone therapy) can delay the need to restart these drugs in men with oligometastactic prostate cancer recurrence.
In practice, this study is open to men whose PSA level (a blood marker of cancer activity) is rising as defined by biochemical recurrence, and who have 1 to 5 areas of cancer spread (1 to 5 metastases defining oligometastatic status) found on a specialized scan (PSMA PET/CT).
Since intensified hormone therapy, including androgen deprivation therapy combined with a next-generation hormone therapy, represents the standard treatment strategy for these patients, researchers want to find out if adding radiation therapy can help patients to spend more time off cancer drugs while keeping their cancer under control.
The main questions this trial aims to answer are:
- Does adding radiation therapy to each metastases with or without pelvic area, lengthen the time before participants need to restart drug treatment?
- Does adding radiation therapy increase the number of participants whose PSA drops to a very low level (0.2 ng/mL or lower)?
- Does adding radiation therapy affect participants' quality of life?
Researchers will randomly assign participants (chosen by chance) to receive either enzalutamide (next-generation hormone therapy) plus androgen-deprivation therapy (first-generation hormone therapy ) alone, or the same association of these drugs combined with radiation therapy aimed at each metastases with or without pelvic area.
This comparison will show whether adding radiation therapy helps participants reach a deeper PSA response and go longer without needing cancer drugs.
Participants will:
- Take enzalutamide and androgen-deprivation therapy for 9 months
- Have an equal chance of also receiving radiation therapy to each metastases with or without pelvic area
- Stop drug treatment after 9 months if their PSA drops below 0.2 ng/mL, a level showing the cancer is well controlled
- Restart drug treatment if their PSA rises again during the treatment-free period
- Have regular blood tests and clinic visits to check their PSA, testosterone, and overall health
- Complete short quality-of-life questionnaires during the study
- Take part in a study conducted at several hospitals in Switzerland, Belgium, and France.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Superiority design
| Arm | Type | Receives |
|---|---|---|
| ADT plus Enzalutamide | Active comparator | Drug: Androgen Deprivation Therapy (ADT), Drug: EnzalutamideEnzalutamide 160 mg daily + androgen deprivation therapy for 9 months, suspended if PSA < 0.2 ng/mL, followed by PSA monitoring until progression |
| ADT plus Enzalutamide plus Radiotherapy (MDT +/- WPRT) | Experimental | Radiation: Radiotherapy for MDT ± WPRT, Drug: Androgen Deprivation Therapy (ADT), Drug: EnzalutamideEnzalutamide 160 mg daily + androgen deprivation therapy for 9 months, suspended if PSA < 0.2 ng/mL, followed by PSA monitoring until progression + Radiotherapy for MDT ± WPRT |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Histologically proven initial diagnosis of adenocarcinoma of the prostate
- Rising PSA after local therapy as defined by PSA ≥ 0.2 ng/mL after RP +/- adjuvant/salvage prostate bed RT and at least 2 ng/mL above nadir for primary RT, with a PSADT ≤ 9 months
- Serum Testosterone ≥ 150 ng/dl (6.9343 nM/L)
- On PSMA PET/CT restaging presence of: 1 to 5 distant metastases that are amenable to MDT ± N1 patients (no limit in the number of nodes)
- ECOG performance status 0 - 2
Key exclusion criteria (11 listed)
- More than 5 distant PSMA positive metastases and/or brain or leptomeningeal metastases.
- Prostate recurrence (positive PSMA disease) after primary prostate irradiation
- Prostate bed recurrence (positive PSMA disease) after salvage/adjuvant irradiation
- Pelvic nodal recurrence (positive PSMA disease) after primary WPRT irradiation
- Contraindications to pelvic RT and/or MDT
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Radiotherapy for MDT ± WPRTParticipants receive metastasis-directed therapy (MDT) alone or combined with prostate-bed radiotherapy (PB-RT) and/or whole pelvic radiotherapy (WPRT), as follows (radiotherapy is tailored to each participant's prior curative treatment for prostate cancer, to avoid re-irradiating previously treated volumes) : * Prior radical prostatectomy (RP) alone: MDT plus PB-RT, with or without WPRT. WPRT is mandatory for pelvic nodal involvement (N1) and recommended for node-negative (N0) participants. * Prior RP plus PB-RT: MDT, with or without WPRT. WPRT is mandatory for N1 and recommended for N0 participants. * Prior RP plus PB-RT plus WPRT: MDT alone. * Prior definitive prostate radiotherapy (no prostatectomy): MDT, with or without WPRT. WPRT is mandatory for N1 and recommended for N0 participants. | Radiation | ADT plus Enzalutamide plus Radiotherapy (MDT +/- WPRT) |
| Androgen Deprivation Therapy (ADT)* All arms should receive ADT for a duration of at least 36 weeks. * The prescription of ADT in both treatment arms will be in accordance with standard practice for the indication, the chosen molecules, and the selected doses. * ADT should be suspended at the end of week 36, if PSA < 0.2 ng/mL at week 36. In the off-period, ADT will be restarted with a rise of PSA to ≥ 5 ng/mL after primary RT or to ≥ 2 ng/mL after RP ± postoperative RT. For patients in the off-period with rising PSA < 5 ng/mL after primary RT or < 2ng/mL after RP * postoperative RT, the decision to restart treatment is led to each investigator. * ADT should be continued until progression at the end of week 36, if PSA ≥ 0.2 ng/mL at week 36. | Drug | ADT plus Enzalutamide, ADT plus Enzalutamide plus Radiotherapy (MDT +/- WPRT) |
| Enzalutamide* All arms should receive enzalutamide 160mg daily for a duration of at least 36 weeks. * Enzalutamide should be suspended at the end of week 36, if PSA < 0.2 ng/mL at week 36. In the off-period, Enzalutamide will be restarted with a rise of PSA to ≥ 5 ng/mL after primary RT or to ≥ 2 ng/mL after RP ± postoperative RT. For patients in the off-period with rising PSA < 5 ng/mL after primary RT or < 2ng/mL after RP ± postoperative RT, the decision to restart treatment is led to each investigator. * Enzalutamide should be continued until progression at the end of week 36, if PSA ≥ 0.2 ng/mL at week 36. | Drug | ADT plus Enzalutamide, ADT plus Enzalutamide plus Radiotherapy (MDT +/- WPRT) |
Primary outcome
Time to first re-initiation of treatment
Time frame: From the start of Androgen Deprivation Therapy plus Enzalutamide to 5 years after this date
• Time to first re-initiation of treatment calculated from randomization to the occurrence of one of the following events: * PSA ≥ 0.2 ng/mL at week 36 (treatment is continued until progression), * For patients in the off-period, a rise of PSA to ≥ 5 ng/mL after primary RT or to ≥ 2 ng/mL after RP ± postoperative RT (treatment is restarted as per EMBARK criteria) * For patients in the off-period with rising PSA < 5 ng/mL after primary RT or <2ng/mL after RP ± postoperative RT, the investigator decision to start same or new treatment. Death in the absence of progressive disease will be considered as a competing risk for this endpoint.
11 secondary outcomes
Time to PSA progression
Time frame: From the start of Androgen Deprivation Therapy plus Enzalutamide to 5 years after this date
PFS (Progression-Free Survival)
Time frame: From the start of Androgen Deprivation Therapy plus Enzalutamide to 5 years after this date
MFS (Metastasis-Free Survival)
Time frame: From the start of Androgen Deprivation Therapy plus Enzalutamide to 5 years after this date
OS (Overall Survival)
Time frame: From the start of Androgen Deprivation Therapy plus Enzalutamide to 5 years after this date
PSA response
Time frame: From the start of Androgen Deprivation Therapy plus Enzalutamide to 5 years after this date
Pattern of progression
Time frame: From the start of Androgen Deprivation Therapy plus Enzalutamide to 5 years after this date
Time to castration-resistant disease
Time frame: From the start of Androgen Deprivation Therapy plus Enzalutamide to 5 years after this date
Adverse events
Time frame: From the start of Androgen Deprivation Therapy plus Enzalutamide to 5 years after this date
Quality of life (QoL) - EORTC QLQ-C30
Time frame: From the start of Androgen Deprivation Therapy plus Enzalutamide to 5 years after this date
Quality of Life - EORTC QLQ-PR25
Time frame: From the start of Androgen Deprivation Therapy plus Enzalutamide to 5 years after this date
Quality of Life - EORTC IL-249
Time frame: From the start of Androgen Deprivation Therapy plus Enzalutamide to 5 years after this date
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Aug 2026.
- Background: PubMed 41672869Nguyen PL, Kollmeier MA, Rathkopf DE, Hoffman KE, Zurita AJ, Spratt DE, Dess RT, Liauw SL, Szmulewitz RZ, Einstein DJ, Bubley GJ, Yu JB, An Y, Wong AC, Feng FY, McKay RR, Rose BS, Shin KY, Kibel AS, Taplin ME. FORMULA-509: A Multicenter Randomized Trial of Postprostatectomy Salvage Radiotherapy and 6 months of a GNRH Agonist with Either Bicalutamide or Abiraterone Acetate plus Prednisone and Apalutamide. Eur Urol. 2026 Feb 10:S0302-2838(25)04854-7. doi: 10.1016/j.eururo.2025.12.001. Online ahead of print.
- Background: PubMed 41643695Tang C, Sherry AD, Hwang H, Farris DP, Francolini G, Di Cataldo V, Livi L, Tran P, Corn PG, Aparicio A, Simontacchi G, Kiess AP, Wang JH, Fonteyne V, Bultijnck R, Phillips R, Deek MP, Olson R, Harrow S, Marvaso G, Lorubbio C, Jereczek-Fossa BA, Ludmir EB, Blanchard P, Warner A, Sun R, Palma DA, Ost P. Metastasis-directed therapy and standard of care versus standard of care for oligometastatic prostate cancer (WOLVERINE): a systematic review and individual patient data meta-analysis from the X-MET collaboration. Lancet Oncol. 2026 Feb;27(2):181-190. doi: 10.1016/S1470-2045(25)00658-8.
- Background: PubMed 37022702Tang C, Sherry AD, Haymaker C, Bathala T, Liu S, Fellman B, Cohen L, Aparicio A, Zurita AJ, Reuben A, Marmonti E, Chun SG, Reddy JP, Ghia A, McGuire S, Efstathiou E, Wang J, Wang J, Pilie P, Kovitz C, Du W, Simiele SJ, Kumar R, Borghero Y, Shi Z, Chapin B, Gomez D, Wistuba I, Corn PG. Addition of Metastasis-Directed Therapy to Intermittent Hormone Therapy for Oligometastatic Prostate Cancer: The EXTEND Phase 2 Randomized Clinical Trial. JAMA Oncol. 2023 Jun 1;9(6):825-834. doi: 10.1001/jamaoncol.2023.0161.
- Background: PubMed 39752157Holzgreve A, Armstrong WR, Clark KJ, Benz MR, Smith CP, Djaileb L, Gafita A, Thin P, Nickols NG, Kishan AU, Rettig MB, Reiter RE, Czernin J, Calais J. PSMA-PET/CT Findings in Patients With High-Risk Biochemically Recurrent Prostate Cancer With No Metastatic Disease by Conventional Imaging. JAMA Netw Open. 2025 Jan 2;8(1):e2452971. doi: 10.1001/jamanetworkopen.2024.52971.
- Background: PubMed 36404204Bukavina L, Luckenbaugh AN, Hofman MS, Hope T, Kamran SC, Murphy DG, Yamoah K, Ost P. Incorporating Prostate-specific Membrane Antigen Positron Emission Tomography in Management Decisions for Men with Newly Diagnosed or Biochemically Recurrent Prostate Cancer. Eur Urol. 2023 Jun;83(6):521-533. doi: 10.1016/j.eururo.2022.10.024. Epub 2022 Nov 18.
- Background: PubMed 41124201Shore ND, Luz MA, De Giorgi U, Gleave M, Gotto GT, Pieczonka CM, Haas GP, Kim CS, Ramirez-Backhaus M, Rannikko A, Kalac M, Sridharan S, Rosales M, Tang Y, Tutrone RF Jr, Venugopal B, Villers A, Woo HH, Wang F, Freedland SJ. Improved Survival with Enzalutamide in Biochemically Recurrent Prostate Cancer. N Engl J Med. 2026 Feb 5;394(6):563-575. doi: 10.1056/NEJMoa2510310. Epub 2025 Oct 19.
- Background: PubMed 22931259Crook JM, O'Callaghan CJ, Duncan G, Dearnaley DP, Higano CS, Horwitz EM, Frymire E, Malone S, Chin J, Nabid A, Warde P, Corbett T, Angyalfi S, Goldenberg SL, Gospodarowicz MK, Saad F, Logue JP, Hall E, Schellhammer PF, Ding K, Klotz L. Intermittent androgen suppression for rising PSA level after radiotherapy. N Engl J Med. 2012 Sep 6;367(10):895-903. doi: 10.1056/NEJMoa1201546.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Tatiana Terrot contact
Thomas Zilli, MD principal investigator
IOSI-EOC
Bertrand Tombal, MD, PhD study chair
Urology, Cliniques Universitaires Saint Luc, Bruxelles, Belgium
Piet Ost, MD, PhD study chair
Department of Human Structure and Repair, Ghent University, Ghent, Belgium; Department of Radiation Oncology, Iridium Network, Wilrijk, Belgium
19 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Radiotherapy for MDT ± WPRT, Androgen Deprivation Therapy (ADT) and Enzalutamide in people with Prostatic Neoplasms and Biochemical Recurrence, run by Ente Ospedaliero Cantonale, Bellinzona at 19 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 24 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 19 sites in Belgium, Switzerland, France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Thomas Zilli, MD (+ 41 918118675, thomas.zilli@eoc.ch), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to first re-initiation of treatment (time frame: From the start of Androgen Deprivation Therapy plus Enzalutamide to 5 years after this date). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07782112, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Aug 2026.