Shorter apalutamide or enzalutamide treatment for low-volume, hormone-sensitive metastatic prostate cancer

Apa/Enza Short Study: Shortened 12 Months Duration of Androgen Receptor Signaling Agent in Combination With Androgen Deprivation Therapy in Patients With Low Volume Castration-sensitive Prostate Cancer: a Randomized Nationwide Study

This study will see if stopping apalutamide or enzalutamide after 12 months (and restarting only if PSA rises) works as well as continuing the drug for men with low-volume, hormone-sensitive metastatic prostate cancer.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 400 (estimated)
• Ages: 18 Years and up
• Sex: Male
• Sponsor: Erasmus Medical Center (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy
• Locations: 26 sites (Alkmaar and 25 other locations)
• Trial ID: NCT07260435 on ClinicalTrials.gov

What this trial studies

Men with low-volume, de novo metastatic, hormone-sensitive prostate cancer who have completed 12 months of androgen receptor pathway inhibitor (apalutamide or enzalutamide) plus ADT are randomized to either continue ARPI with ADT or stop ARPI after 12 months while remaining on ADT, with the option to restart ARPI if a confirmed PSA rise occurs. Randomization occurs after the first 12 months of therapy and PSA confirmation of progression requires a repeat sample at least four weeks after the initial rise. The trial is designed as a Phase 3 non-inferiority comparison to determine whether a fixed 12-month ARPI strategy provides similar disease control while reducing cumulative toxicity and costs. Imaging for low-volume status may include bone scan/CT or PSMA-PET and eligibility requires ECOG 0–2 and initiation of ADT within six weeks before inclusion.

Who should consider this trial

Good fit: Men with low-volume, de novo metastatic, hormone-sensitive prostate adenocarcinoma who have completed 12 months of apalutamide or enzalutamide with ADT and are fit for ARPI therapy are ideal candidates.

Not a fit: Patients with high-volume or visceral metastatic disease, those who progressed during initial ARPI therapy, or those unable to adhere to close PSA monitoring are unlikely to benefit from the shorter-course approach.

Why it matters

Potential benefit: If successful, patients could have similar cancer control with shorter ARPI exposure, leading to fewer side effects and lower treatment costs.

How similar studies have performed: Intermittent androgen-deprivation approaches have shown mixed results historically, and applying a fixed 12-month ARPI stop with restart on PSA rise is a relatively novel strategy that is not yet proven.

Eligibility criteria

Inclusion Criteria:

* Male and ≥18 years of age
* Capable of understanding and complying with protocol requirements and able to understand and sign the informed consent form
* Histological diagnosis of prostate adenocarcinoma
* Low volume de novo metastatic disease (M1a or M1b) defined as anything other than fitting the criteria for high-volume metastatic disease, e.g., four or more bone lesions with one or more lesions in any body structure beyond the spine or pelvis, or visceral disease (non-nodal). This has been assessed by either bone scan and computed tomography (CT), or PSMA-PET scan. Low-volume disease has subsequently been confirmed by the local (multidisciplinary) team after consideration of the available imaging results as per the standard imaging protocol for the site.
* ADT initiated within 6 weeks prior to inclusion
* Eastern Cooperative Oncology Group (ECOG) performance scale status of 0, 1 or 2
* Fit for treatment with apalutamide or enzalutamide according to treating physician

Exclusion Criteria:

* Pathological finding consistent with small cell, ductal or neuroendocrine carcinoma of the prostate
* Other prior malignancy less than or equal to 5 years prior to randomization except for squamous or basal cell skin carcinoma or non-invasive superficial bladder cancer
* History of seizures or medications known to lower seizure threshold
* Any other prior treatment for prostate cancer other than ADT (e.g., other next generation anti-androgens or other CYP17 inhibitors, chemotherapy, immunotherapy, or radiopharmaceutical agents)
* ADT started more than 6 weeks before inclusion

Where this trial is running

Alkmaar and 25 other locations

• Noordwest Ziekenhuisgroep — Alkmaar, Netherlands (Recruiting)
• Meander MC Amersfoort — Amersfoort, Netherlands (Not_yet_recruiting)
• Amsterdam Universitair Medisch Centrum — Amsterdam, Netherlands (Not_yet_recruiting)
• Antoni van Leeuwenhoek — Amsterdam, Netherlands (Not_yet_recruiting)
• Wilhelmina Ziekenhuis Assen — Assen, Netherlands (Recruiting)
• Rode Kruis Ziekenhuis — Beverwijk, Netherlands (Recruiting)
• Deventer Ziekenhuis — Deventer, Netherlands (Recruiting)
• Catharina Ziekenhuis — Eindhoven, Netherlands (Recruiting)
• Treant Zorggroep — Emmen, Netherlands (Recruiting)
• Medisch Spectrum Twente — Enschede, Netherlands (Recruiting)
• Admiraal de Ruyter ziekenhuis — Goes, Netherlands (Recruiting)
• Universitair Medisch Centrum Groningen — Groningen, Netherlands (Recruiting)
• Spaarne Gasthuis — Haarlem, Netherlands (Recruiting)
• Ziekenhuisgroep Twente — Hengelo, Netherlands (Recruiting)
• Tergooi MC — Hilversum, Netherlands (Not_yet_recruiting)
• Frisius MC Leeuwarden — Leeuwarden, Netherlands (Recruiting)
• Maastricht UMC — Maastricht, Netherlands (Recruiting)
• Canisius Wilhelmina Ziekenhuis — Nijmegen, Netherlands (Recruiting)
• Laurentius Ziekenhuis — Roermond, Netherlands (Recruiting)
• Bravis Ziekenhuis — Roosendaal, Netherlands (Recruiting)
• Erasmus mc — Rotterdam, Netherlands (Recruiting)
• Fransicus Gasthuis & Vlietland — Rotterdam, Netherlands (Recruiting)
• Maasstad Ziekenhuis — Rotterdam, Netherlands (Recruiting)
• HagaZiekenhuis — The Hague, Netherlands (Recruiting)
• St. Antonius Ziekenhuis — Utrecht, Netherlands (Not_yet_recruiting)
• VieCuri Medisch Centrum — Venlo, Netherlands (Recruiting)

Study contacts

• Study coordinator: Dr. N. Beije

Conditions Prostate Cancer