Intermittent hormone suppression with AR pathway inhibitors for metastatic prostate cancer

Intermittent Androgen Deprivation Therapy in the Era of AR Pathway Inhibitors; a Phase 3 Pragmatic Randomized Trial.

Phase 3 Interventional European Organisation for Research and Treatment of Cancer - EORTC · NCT05974774

This trial will test whether planned treatment breaks from continuous androgen‑deprivation plus AR pathway inhibitors work as well as staying on continuous therapy for men with metastatic hormone‑naïve prostate cancer who have very low PSA after 6–12 months of treatment.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment1600 (estimated)
Ages18 Years to 100 Years
SexMale
SponsorEuropean Organisation for Research and Treatment of Cancer - EORTC Research network
Drugs / interventionsradiation
Locations9 sites (Copenhagen and 8 other locations)
Trial IDNCT05974774 on ClinicalTrials.gov

What this trial studies

This is a randomized phase 3 trial comparing intermittent multiple androgen blockade (iMAB) versus continuous multiple androgen blockade (cMAB) in men with metastatic hormone‑naïve prostate cancer who achieve a PSA ≤0.2 ng/mL after 6–12 months of ADT combined with an AR pathway inhibitor. Patients who previously received docetaxel or radiotherapy may be eligible and participants are randomized to either planned treatment holidays or continued therapy until progression. The primary goal is to determine whether intermittent therapy provides a similar overall survival while reducing treatment duration, side effects, and resource use. Secondary objectives include effects on quality of life, toxicity profiles, and time to progression.

Who should consider this trial

Good fit: Ideal candidates are men with metastatic hormone‑naïve prostate cancer who have been on ADT plus an AR pathway inhibitor for 6–12 months and have a PSA ≤0.2 ng/mL, including those who received prior docetaxel or radiotherapy.

Not a fit: Patients unlikely to benefit include those with planned local radiation plus 2–3 years of hormone therapy for M1a disease, men who have had bilateral orchiectomy, those with interfering concurrent malignancies, or patients who have not met the PSA or treatment‑duration criteria.

Why it matters

Potential benefit: If successful, intermittent therapy could maintain survival while reducing side effects, improving quality of life, and lowering treatment burden and costs.

How similar studies have performed: Intermittent ADT showed comparable survival to continuous ADT in some older trials before widespread use of AR pathway inhibitors, but combining intermittent schedules with modern ARPIs is relatively novel and unproven in phase 3.

Eligibility criteria

Show full inclusion / exclusion criteria
Inclusion Criteria:

* Patient treated with ADT and an ARPI for mHNPC for 6-12 months and presenting with a PSA ≤ 0.2 ng/mL Note: Patient may have received docetaxel and radiotherapy of the prostate and metastases Note: Patients with synchronous or metachronous metastases, high volume/risk or low volume/risk who fulfil the criteria can be included.
* Before patient 's enrolment, written informed consent must be given according to ICH/GCP, and national/local regulations

Exclusion Criteria:

* Patients with M1a on modern imaging technique (PET-Choline or -PSMA or Whole Body MRI) for whom radiation therapy and 2-3 years of hormone therapy is planned
* Patients who underwent or will undergo a bilateral orchiectomy
* Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment for this trial
* Patients who have received a systemic anti-prostate cancer treatment not approved by EMA together with MAB or a radical prostatectomy for M1 disease
* Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be assessed and discussed with the patient before the enrolment in the trial

Where this trial is running

Copenhagen and 8 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Prostate CancerMetastatic hormone-naïve prostate cancer
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.