Best Salvage Treatment for High-risk Relapsing Prostate Cancer (PEACE-9 - ESCALATE-RT)

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.

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.

Conditions

• Prostatic Neoplasms
• Biochemical Recurrence
• Oligometastatic Prostate Cancer

Interventions

RADIATION

Radiotherapy for MDT ± WPRT

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.

DRUG

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

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.

Sponsors & Collaborators

• Clinical Trial Unit Ente Ospedaliero Cantonale

  collaborator OTHER

• Ente Ospedaliero Cantonale, Bellinzona

  lead OTHER

Principal Investigators

• Thomas Zilli, MD · IOSI-EOC

• Bertrand Tombal, MD, PhD · Urology, Cliniques Universitaires Saint Luc, Bruxelles, Belgium

• Piet Ost, MD, PhD · Department of Human Structure and Repair, Ghent University, Ghent, Belgium; Department of Radiation Oncology, Iridium Network, Wilrijk, Belgium

• Silke Gillessen, MD · IOSI-EOC

• Piet Dirix, MD, PhD · Department of Radiation Oncology, Iridium Network, Wilrijk, Belgium

• Salvatore Cozzi, MD · IOSI-EOC

• Nicolas Vial, MD · University Hospital of Saint-Etienne

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

MALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-11-30

Primary Completion

2030-07-31

Completion

2030-07-31

Countries

• Belgium
• France
• Switzerland

Study Locations