Intermittent Androgen Deprivation Therapy in the Era of AR Pathway Inhibitors

NCT05974774 | Recruiting Phase 3

• 1 other identifier: EORTC 2238
• Study Type: interventional
• Target: 1,600
• Locations: 3 countries
• Sites: 9

Brief Summary

This study addresses the global topic of treatment optimization, i.e. achieving similar benefit while reducing the duration of treatment, hence hoping to decrease the burden of side-effects, improve quality-of life and reduce resource utilization. The primary goal of de-escalation is to investigate whether using an intermittent regime results in a similar OS to continuous treatment.

Conditions

Prostate Cancer

Keywords

Metastatic hormone-naïve prostate cancer

Outcome Measures

Primary Outcomes (2)

• overall survival

  the overall survival (OS) using an iMAB regimen is non-inferior to continuous treatment.

  10 years from randomisation

• proportion of patients who do not restart their hormonal therapy within 1 year of interrupting their MAB therapy (given as part of the induction phase)

  proportion of patients who do not restart within 1 year of interrupting their MAB therapy (given as part of the induction phase) is not less than 70%

  1 year from stopping the MAB therapy

Secondary Outcomes (7)

• occurrence of adverse events

  10 years from randomisation

• Time spent on MAB treatment

  10 years from randomisation

• Time to next systemic prostate cancer therapy

  10 years from randomisation

• The magnitude of change in HRQoL

  60 months from randomisation

• The magnitude of change in HRQoL

  60 months from randomisation

Study Arms (2)

Arm A - continuous treatment

ACTIVE COMPARATOR

Arm A (cMAB): ADT (LHRH agonist or antagonist) + ARPI (abiraterone or enzalutamide or apalutamide or darolutamide) continuously until start of a new anti-cancer therapy.

Drug: cMAB

Arm B - intermittent treatment

EXPERIMENTAL

Arm B (iMAB): no further treatment, including ADT and ARPI; decision to restart ADT (LHRH agonist or antagonist) and the initial ARPI (abiraterone, enzalutamide, apalutamide or darolutamide) is left at Investigator discretion.

Drug: iMAB

Interventions

iMAB DRUG

no treatment until significant PSA increase as per treating physician at which point patient restarts ADT (LHRH agonist or antagonist) + ARPI (abiraterone or enzalutamide or apalutamide or darolutamide). Once PSA \< 0.2 ng/mL, treatment stops again.

Also known as: intermittent maximum androgen blockade

Arm B - intermittent treatment

cMAB DRUG

LHRH agonist or antagonist + ARPI (abiraterone or enzalutamide or apalutamide or darolutamide)

Also known as: continuous maximum androgen blockade

Arm A - continuous treatment

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead
• Cancer Trials Ireland: collaborator
• UNICANCER: collaborator
• Spanish Oncology Genito-Urinary Group: collaborator

Study Sites (9)

University Hospitals Copenhagen - Rigshospitalet

Copenhagen, Denmark

RECRUITING

Centre Francois Baclesse

Caen, 14076, France

RECRUITING

Institut Daniel Hollard

Grenoble, France

RECRUITING

Clinique La Croix Du Sud

Quint-Fonsegrives, France

RECRUITING

CHU de Toulouse - Institut Claudius Regaud - IUCT oncopole

Toulouse, France

RECRUITING

Gustave Roussy

Villejuif, 94805, France

RECRUITING

Hospital De La Santa Creu I Sant Pau

Barcelona, 08041, Spain

RECRUITING

Hospital Universitario San Carlos

Madrid, Spain

RECRUITING

Hospital Universitario Puerta De Hierro

Majadahonda, Spain

RECRUITING

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

7-iodo-8-hydroxy-3-methyl-1-(4-azidophenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Officials

• Bertrand Tombal, Prof

  Cliniques Universitaires de Saint Luc

  STUDY CHAIR

• Silke Gillessen, Prof

  Oncology Institute of Southern Switzerland - Ospedale San Giovanni

  STUDY CHAIR

Central Study Contacts

EORTC

CONTACT

+3227741611; eortc@eortc.org

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 26, 2023
• First Posted: August 3, 2023
• Study Start: May 23, 2025
• Primary Completion (Estimated): May 23, 2035
• Study Completion (Estimated): June 1, 2039
• Last Updated: September 19, 2025

Record last verified: 2025-09

Locations

FR (5); ES (3); DK (1)