Prostate CancerPhase 3NCT05974774
Intermittent Androgen Deprivation Therapy in the Era of AR Pathway Inhibitors
A Phase 3 study testing iMAB and cMAB in people with Prostate Cancer, run by European Organisation for Research and Treatment of Cancer - EORTC at 9 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 100 years, men only
- Conditions the study is for
- Prostate Cancer
- What is being tested?
- iMAB and cMAB
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,600 participants
- Where
- 9 sitesin 3 countries
- Study dates
- 23 May 2025to 1 Jun 2039
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
9 sites in 3 countries. Contact the study team or a site near you to ask about taking part.
9 sites in 3 countries
France5 sites, 5 recruiting
- Recruiting
Centre Francois Baclesse
Caen, 14076
Florence Joly, Dr
- Recruiting
Institut Daniel Hollard
Grenoble
Valentine Ruste, Dr
- Recruiting
Clinique La Croix Du Sud
Quint-Fonsegrives
Guillaume Ploussard, Dr
- Recruiting
CHU de Toulouse - Institut Claudius Regaud - IUCT oncopole
Toulouse
Loic Mourey, Dr
- Recruiting
Gustave Roussy
Villejuif, 94805
Anna Patrikidou, Dr
Spain3 sites, 3 recruiting
- Recruiting
Hospital De La Santa Creu I Sant Pau
Barcelona, 08041
Pablo Maroto, Dr
- Recruiting
Hospital Universitario San Carlos
Madrid
Javier Puente, Dr
- Recruiting
Hospital Universitario Puerta De Hierro
Majadahonda
Aranzazu Gonzalez del Alba, Dr
Denmark1 site, 1 recruiting
- Recruiting
University Hospitals Copenhagen - Rigshospitalet
Copenhagen
Martin Andreas Roeder Martin Andreas, Dr
About this study
Official title: Intermittent Androgen Deprivation Therapy in the Era of AR Pathway Inhibitors; a Phase 3 Pragmatic Randomized Trial.
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.
Read the detailed description
Prostate cancer is known to be dependent on testicular and adrenal androgens and the earliest identified treatments were the suppression of the body's production of testosterone. Then came the development of drugs able to block the androgen receptors that multiplied on the cancer cell membranes. The combination of these drugs presently approved by the EMA for first line treatment of mHNPC are understood to be given maximum androgen blockage and to be used until progression. All have been shown to positively impact overall survival. For patients, however, the consequences of continuous intensified MAB, and thereby testosterone suppression, have impacted their quality of life, especially in the form of fatigue, emotional distress, decrease of libido and loss of sexual function. This is in addition to toxicities linked to the mechanisms of these drugs which include cardiovascular diseases, cognitive effects and loss of bone mineral density.
Treatment optimization is rarely addressed by clinical trials run for registration purposes. Toxicity is subsumed under efficacy and keeping the cancer at bay or controlled at any cost. Overall patient experience is not taken into account when determining what is an acceptable trade-off. Intermittent treatment or drug holiday are options to manage drug toxicities but longer off-treatment periods remain rare due to the fear of losing efficacy.
Prostate cancer is an ideal setting to study the benefits of intermittent treatment as PSA levels have been shown to be a good indicator of cancer status. By holding androgen blockade after good PSA response, patients get the opportunity of seeing an improvement in their quality of life as testosterone levels slowly recover. The longer a patient stays off treatment, the more improvements to his overall wellbeing can be felt. Monitoring PSA levels provides an early signal to cancer regrowth and allows for the restart of MAB when it becomes necessary.
While improving the patient's quality of life, there is as yet no indication as to the possible impact of this approach on overall survival. Alternating off/on treatment could delay both the start of the next line of treatment and the development of castration resistance but the absence of constant androgen suppression could also have the opposite effect and precipitate new alternatives to cancer cells testosterone dependence.
This trial will randomize patients to either continue with their treatment as prescribed or to stop treatment until PSA levels indicate the necessity of restarting suppression. The latter group can stop treatment again when PSA levels reaches 0.2 ng/mL or lower. There is a need to investigate whether the benefit to patient's lives of holding long-term treatment will outweigh the risks of shortening overall survival. This trial is being done to allow both patients and their treating teams to have the data needed to make an informed decision on the best treatment approach.
- Conditions
- Prostate Cancer
- Being tested
- iMAB, cMAB
- Keywords
- Metastatic hormone-naïve prostate cancer
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
iMABDrug
Also called intermittent maximum androgen blockade
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.
cMABDrug
Also called continuous maximum androgen blockade
LHRH agonist or antagonist + ARPI (abiraterone or enzalutamide or apalutamide or darolutamide)
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: iMAB |
What is being measured
The primary outcome is the main question the study is designed to answer.
overall survival
the overall survival (OS) using an iMAB regimen is non-inferior to continuous treatment.
Measured: 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%
Measured: 1 year from stopping the MAB therapy
Secondary outcomes (7)
occurrence of adverse events
Safety according to the CTCAE (NCI Common Terminology Criteria for Adverse Events) Version 5.0 for toxicity and Serious Adverse Event reporting.
Measured: 10 years from randomisation
Time spent on MAB treatment
the overall time in months that the patient was on MAB treatment
Measured: 10 years from randomisation
Time to next systemic prostate cancer therapy
the overall time in months until the patient began the next systemic prostate cancer therapy
Measured: 10 years from randomisation
The magnitude of change in HRQoL
The magnitude of change in HRQoL in terms of physical functioning from EORTC QLQ-C30
Measured: 60 months from randomisation
The magnitude of change in HRQoL
The magnitude of change in HRQoL in terms of sexual activity, physical fatigue and pain characteristics from the IL249 item list; To cover all important HRQoL domains and to have more granularity on some of the selected domains, additional HRQoL concepts are searched in the EORTC item library. This resulted in the inclusion of an additional scale that measures the pain characteristics.
The selected scale and corresponding items address the pain characteristics (the nature of the pain: constant versus intermittent and whether the pain can be relieved by pain medications)
Measured: 60 months from randomisation
health utility derived from the QLQ-C30 questionnaires data
Health utility derived from patient reported QLQ-C30 data and patient demographics;Health utilities summarize a patient's overall health status, and this parameter can be applied in cost-effectiveness analyses. Published mapping algorithms can be used to calculate health utility based on the collected QLQ-C30 data, either directly or indirectly. The indirect algorithms first maps QLQ-C30 scores to European Quality-of-Life-5 Dimensions (EQ-5D) scores and then to health utility scores. The collected HRQoL data using QLQ-C30 will be mapped first to EQ-5D scores using an established mapping approach from the literature, and then further translated to health utility values for each study subject and at each assessment of HRQoL, taking into account published national value sets for this conversion.
Measured: 10 years from randomisation
Prostate cancer specific survival
Prostate cancer specific survival will be computed from the date of randomization to the date of death due to prostate cancer. Participants who died from other causes will be considered as having a competing event at this time. Participants who are still alive at the analysis cut-off date are censored at the last date known to be on protocol treatment (before the cut-off date).
Measured: 10 years from randomisation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Aug 2023
- Study start23 May 2025
- Primary completion23 May 2035 (estimated)
- Study completion1 Jun 2039 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- More trials run by European Organisation for Research and Treatment of Cancer - EORTCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1,600 participants (estimated)
Sponsor and investigators
- Sponsor type
- Research network
- Collaborators
- Cancer Trials Ireland, UNICANCER, Spanish Oncology Genito-Urinary Group
- Responsible party
- Sponsor
- Investigators
- Bertrand Tombal, Prof, Study chair, Cliniques Universitaires de Saint LucSilke Gillessen, Prof, Study chair, Oncology Institute of Southern Switzerland - Ospedale San Giovanni
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05974774
- Sponsor's protocol ID
- EORTC 2238
- Status last verified
- Sep 2025
- First submitted
- 26 Jun 2023
- Last updated
- 19 Sep 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intermittent Androgen Deprivation Therapy in the Era of AR Pathway Inhibitors; a Phase 3 Pragmatic Randomized Trial.
- ClinicalTrials.gov ID
- NCT05974774
- Acronym / sponsor ID
- EORTC 2238
- Conditions
- Prostate Cancer
- Keywords
- Metastatic hormone-naïve prostate cancer
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 1,600 participants (estimated)
- Lead sponsor
- European Organisation for Research and Treatment of Cancer - EORTCResearch network
- Collaborators
- Cancer Trials Ireland, UNICANCER, Spanish Oncology Genito-Urinary Group
- Study start
- 23 May 2025 (actual)
- Primary completion
- 23 May 2035 (estimated)
- Study completion
- 1 Jun 2039 (estimated)
- First posted
- 3 Aug 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Prostate cancer is known to be dependent on testicular and adrenal androgens and the earliest identified treatments were the suppression of the body's production of testosterone. Then came the development of drugs able to block the androgen receptors that multiplied on the cancer cell membranes. The combination of these drugs presently approved by the EMA for first line treatment of mHNPC are understood to be given maximum androgen blockage and to be used until progression. All have been shown to positively impact overall survival. For patients, however, the consequences of continuous intensified MAB, and thereby testosterone suppression, have impacted their quality of life, especially in the form of fatigue, emotional distress, decrease of libido and loss of sexual function. This is in addition to toxicities linked to the mechanisms of these drugs which include cardiovascular diseases, cognitive effects and loss of bone mineral density.
Treatment optimization is rarely addressed by clinical trials run for registration purposes. Toxicity is subsumed under efficacy and keeping the cancer at bay or controlled at any cost. Overall patient experience is not taken into account when determining what is an acceptable trade-off. Intermittent treatment or drug holiday are options to manage drug toxicities but longer off-treatment periods remain rare due to the fear of losing efficacy.
Prostate cancer is an ideal setting to study the benefits of intermittent treatment as PSA levels have been shown to be a good indicator of cancer status. By holding androgen blockade after good PSA response, patients get the opportunity of seeing an improvement in their quality of life as testosterone levels slowly recover. The longer a patient stays off treatment, the more improvements to his overall wellbeing can be felt. Monitoring PSA levels provides an early signal to cancer regrowth and allows for the restart of MAB when it becomes necessary.
While improving the patient's quality of life, there is as yet no indication as to the possible impact of this approach on overall survival. Alternating off/on treatment could delay both the start of the next line of treatment and the development of castration resistance but the absence of constant androgen suppression could also have the opposite effect and precipitate new alternatives to cancer cells testosterone dependence.
This trial will randomize patients to either continue with their treatment as prescribed or to stop treatment until PSA levels indicate the necessity of restarting suppression. The latter group can stop treatment again when PSA levels reaches 0.2 ng/mL or lower. There is a need to investigate whether the benefit to patient's lives of holding long-term treatment will outweigh the risks of shortening overall survival. This trial is being done to allow both patients and their treating teams to have the data needed to make an informed decision on the best treatment approach.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A - continuous treatment | Active comparator | Drug: cMABArm A (cMAB): ADT (LHRH agonist or antagonist) + ARPI (abiraterone or enzalutamide or apalutamide or darolutamide) continuously until start of a new anti-cancer therapy. |
| Arm B - intermittent treatment | Experimental | Drug: iMABArm 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. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| iMABAlso: intermittent maximum androgen blockadeno 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. | Drug | Arm B - intermittent treatment |
| cMABAlso: continuous maximum androgen blockadeLHRH agonist or antagonist + ARPI (abiraterone or enzalutamide or apalutamide or darolutamide) | Drug | Arm A - continuous treatment |
Primary outcome
overall survival
Time frame: 10 years from randomisation
the overall survival (OS) using an iMAB regimen is non-inferior to continuous treatment.
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)
Time frame: 1 year from stopping the MAB therapy
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%
7 secondary outcomes
occurrence of adverse events
Time frame: 10 years from randomisation
Time spent on MAB treatment
Time frame: 10 years from randomisation
Time to next systemic prostate cancer therapy
Time frame: 10 years from randomisation
The magnitude of change in HRQoL
Time frame: 60 months from randomisation
The magnitude of change in HRQoL
Time frame: 60 months from randomisation
health utility derived from the QLQ-C30 questionnaires data
Time frame: 10 years from randomisation
Prostate cancer specific survival
Time frame: 10 years from randomisation
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Bertrand Tombal, Prof study chair
Cliniques Universitaires de Saint Luc
Silke Gillessen, Prof study chair
Oncology Institute of Southern Switzerland - Ospedale San Giovanni
9 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing iMAB and cMAB in people with Prostate Cancer, run by European Organisation for Research and Treatment of Cancer - EORTC at 9 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 19 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in France, Spain, Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact EORTC (+3227741611, eortc@eortc.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
overall survival (time frame: 10 years from randomisation). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2025.