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

Phase 3Not Yet RecruitingNCT07782112

Ente Ospedaliero Cantonale, Bellinzona140 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Interventions

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.

Eligibility

Sex: MALEMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (19)

AZorg Aalst

Aalst, Belgium

Iridium Netwerk

Antwerp, Belgium

AZ Sint-Jan

Bruges, Belgium

Institut Bordet - HUB Brussel

Brussels, Belgium

Jessa ziekenhuis

Hasselt, Belgium

AZ Groeninge

Kortrijk, Belgium

AZ Sint-Maarten Mechelen

Mechelen, Belgium

Institut Bergonié

Bordeaux, France

Centre Oscar Lambret

Lille, France

CHU de Saint-Etienne

Saint-Etienne, France

...and 9 more locations

Outcomes

Primary Outcomes

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.