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NCT Number: NCT07782112

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

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.

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Key information

Conditions

Prostatic Neoplasms Biochemical Recurrence Genital Diseases Genital Diseases, Male Genital Neoplasms, Male Male Urogenital Diseases Neoplasms Neoplasms by Site Oligometastatic Prostate Cancer Prostatic Diseases Urogenital Diseases Urogenital Neoplasms

Age range

18 year and older

Sex eligibility

Male

Study type

Interventional

Phase

Phase 3

Primary location

AZorg Aalst, Aalst, Belgium

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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

Exclusion criteria

  • 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
  • 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

Treatment and study plan

Radiotherapy for MDT ± WPRT

Radiation

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.

Enzalutamide

Drug
  • 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.

Primary outcomes

  1. 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.

Secondary outcomes

  1. Time to PSA progression

    Time frame: From the start of Androgen Deprivation Therapy plus Enzalutamide to 5 years after this date

    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.

  2. PFS (Progression-Free Survival)

    Time frame: From the start of Androgen Deprivation Therapy plus Enzalutamide to 5 years after this date

    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).

  3. MFS (Metastasis-Free Survival)

    Time frame: From the start of Androgen Deprivation Therapy plus Enzalutamide to 5 years after this date

    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.

  4. OS (Overall Survival)

    Time frame: From the start of Androgen Deprivation Therapy plus Enzalutamide to 5 years after this date

    OS: defined as the time from randomization to death to any cause.

  5. PSA response

    Time frame: From the start of Androgen Deprivation Therapy plus Enzalutamide to 5 years after this date

    PSA response: defined by a PSA < 0.2 ng/ml at 9 months.

  6. Pattern of progression

    Time frame: From the start of Androgen Deprivation Therapy plus Enzalutamide to 5 years after this date

    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.

  7. Time to castration-resistant disease

    Time frame: From the start of Androgen Deprivation Therapy plus Enzalutamide to 5 years after this date

    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).

  8. Adverse events

    Time frame: From the start of Androgen Deprivation Therapy plus Enzalutamide to 5 years after this date

    Adverse events: acute (during the first 3 months after the end of MDT ± WPRT and late (3 months after the end of MDT ± WPRT).

  9. Quality of life (QoL) - EORTC QLQ-C30

    Time frame: From the start of Androgen Deprivation Therapy plus Enzalutamide to 5 years after this date

    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.

  10. Quality of Life - EORTC QLQ-PR25

    Time frame: From the start of Androgen Deprivation Therapy plus Enzalutamide to 5 years after this date

    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.

  11. Quality of Life - EORTC IL-249

    Time frame: From the start of Androgen Deprivation Therapy plus Enzalutamide to 5 years after this date

    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.

Study contacts

Contact information is provided by the study sponsor or research team.

Tatiana Terrot

CONTACT

[email protected]

Thomas Zilli, MD

CONTACT

[email protected]

+ 41 918118675

Sponsors and collaborators

Lead sponsor

Ente Ospedaliero Cantonale, Bellinzona

Other

Collaborators

  • Clinical Trial Unit Ente Ospedaliero Cantonale

Registry information

Official study 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

Acronym: ESCALATE-RT

Important dates

Study start
2026
Primary completion
2030
Study completion
2030
First posted
Aug 24, 2026
Registry last updated
Aug 24, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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