Metastatic Hormone-sensitive Prostate CancerPhase 3REINFORCENCT07333066
Phase III Randomized International Open Label Clinical Trial of Treatment Intensification With Docetaxel Plus Apalutamide in Patients With Metastatic Hormone-sensitive Prostate Cancer Who Did Not Achieve a Deep PSA Response After Initial Treatment With Apalutamide: REINFORCE Trial.
A Phase 3 study testing Apalutamide (Erleada™) 60 mg or 240 mg tablets and Docetaxel in people with Metastatic Hormone-sensitive Prostate Cancer, run by Alianza multidisciplinar para la investigación de los tumores genitourinarios -GUARD at 56 sites in 5 countries.
Trial summary
This is a phase III, randomized, open-label, multi-center study to assess the efficacy of treatment intensification with docetaxel plus apalutamide and ADT, assessed by event-free survival, in patients with mHSPC who do not achieve deep PSA response (≤0,2 ng/ml or PSA90 response in combination with a PSA ≤ 4 ng/ml)… Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Metastatic Hormone-sensitive Prostate Cancer
- What is being tested?
- Apalutamide (Erleada™) 60 mg or 240 mg tablets and Docetaxel
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 320 participants
- Where
- 56 sitesin 5 countries
- Study dates
- 5 Jun 2026to 31 Mar 2030
- 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 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent. Each patient must sign an informed consent form (ICF) indicating that he understands the purpose of and procedures, required for the study, and is willing to participate in the study.
- Patient must be a man ≥18 years of age.
- Histologically or cytologically confirmed adenocarcinoma of prostate.
- Metastatic hormone-sensitive prostate cancer.
- PSA >5 ng/ml at diagnosis of metastatic disease.
- Patients eligible to continue treatment with apalutamide and ADT and without contra-indication to receive docetaxel.
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- Patients with at least 24 weeks and no more than 30 weeks of apalutamide.
- Patients with a maximum of 12 weeks ADT before apalutamide initiation.
- Lack of achievement of deep PSA response after 24 weeks and no more than 30 weeks of apalutamide. Deep PSA response is defined as PSA ≤ 0.2 ng/ml or PSA response ≥ 90% in combination with a PSA ≤4 ng/ml. Therefore, a non-deep PSA response is defined as PSA > 0.2 ng/ml in combination with a PSA response < 90%, or a PSA response ≥90% in combination with a PSA > 4 ng/ml.
- Patients who have not progressed to apalutamide.
- Patients that are tolerating adequately apalutamide 240 mg daily and with no toxicity higher than G1 at inclusion.
- Be able to swallow whole apalutamide film-coated tablets.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
- Clinical laboratory values at screening:
- hemoglobin ≥10.0 g/dL,
- absolute neutrophil count ≥1.5 × 10*9/L,
- platelet count ≥100 × 109/L, The patient must not have received any growth factor within 4 weeks or a blood transfusion within 7 days of the hematology laboratory sample obtained at screening
- serum alanine aminotransferase and/or aspartate transaminase ≤1.5 × the upper limit of normal (ULN),
- total bilirubin ≤ ULN,
- creatinine ≤2.0 × ULN
- Sexually active men must agree to use an external condom as an effective barrier method and refrain from sperm donation, and their female partners of childbearing potential must practice a highly effective method of contraception during and for 3 months after treatment with apalutamide and for 6 months after treatment with docetaxel.
Who cannot join
- Presence of neuroendocrine histology.
- Apalutamide treatment started more than 30 weeks before inclusion.
- Progression disease by any means, including radiographic, clinical or serological at inclusion.
- Patient who achieves deep PSA response on apalutamide treatment before randomization.
- Previous androgen-pathway receptor inhibitors, including enzalutamide, darolutamide, abiraterone or other ARPI. Previous treatment with first generation antiandrogens (i.e. bicalutamide) is allowed.
- Chemotherapy or immunotherapy for prostate cancer before randomization.
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- Treatment with radiotherapy (external-beam radiation therapy, brachytherapy, or radiopharmaceuticals) within 2 weeks before randomization.
- Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation of the study drugs.
- Contraindication to both computed tomography and magnetic resonance imaging contrast agent.
- Prolonged QT interval defined as QTcF ≥ 480 ms at screening, based on the mean of triplicate 12-lead ECGs performed after at least 5 minutes of rest. Patients with congenital long QT syndrome will also be excluded.
- Any of the following within 6 months before randomization:
- stroke,
- myocardial infarction,
- severe or unstable angina pectoris,
- uncontrolled arrhythmia,
- coronary or peripheral artery bypass graft, or
- congestive heart failure (New York Heart Association class III or IV)
- Peripheral neuropathy ≥ grade 2.
- Uncontrolled hypertension, indicated by resting systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg despite medical management.
- Prior malignancy, except for adequately treated basal-cell or squamous-cell carcinoma of the skin or superficial bladder cancer that had not spread behind the connective-tissue layer (i.e., stage pTis, pTa, or pT1) or any cancer for which treatment had been completed ≥5 years before randomization and from which the patient was disease-free.
- A gastrointestinal disorder or procedure that was expected to interfere significantly with absorption of study drug.
- Active viral hepatitis, known human immunodeficiency virus infection with detectable viral load, or chronic liver disease requiring treatment.
- Previous (within 28 days before the start of study drug or 5 half-lives of the investigational treatment of the previous study, whichever was longer) or concomitant participation in another clinical study with investigational medicinal products.
- Any other serious or unstable illness or medical, social, or psychological condition that could jeopardize the safety of the patient and/or their compliance with study procedures or might interfere with their participation in the study or evaluation of the study results.
Trial locations and contacts
56 sites in 5 countries. Contact the study team or a site near you to ask about taking part.
56 sites in 5 countries
Spain21 sites, 21 recruiting
- Not yet recruiting
Hospital Universitari Vall d´Hebron
Barcelona, Bacelona
Dolores Fenor de la Maza, MD
Dolores Fenor de la Maza, MD
- Not yet recruiting
Hospital Clínic de Barcelona
Barcelona, Barcelona
Marta García de Herreros, MD
Marta García de Herreros, MD
- Not yet recruiting
Hospital del Mar
Barcelona, Barcelona
Alejo Rodríguez-Vida, MD
Alejo Rodríguez-Vida, MD
- Not yet recruiting
Hospital Santa Creu i Sant Pau
Barcelona, Barcelona
Mikel Portu, MD
Mikel Portu, MD
- Not yet recruiting
ICO Badalona
Barcelona, Barcelona
Albert Font, MD
Albert Font, MD
- Not yet recruiting
Hospital Universitario Virgen de las Nieves
Granada, Granada
Raquel Luque, MD
Raquel Luque, MD
- Not yet recruiting
Institut Català d'Oncologia (ICO) L´Hospitalet de Llobregat
L'Hospitalet de Llobregat, Barcelona
Jose María Piulats, MD
Jose María Piulats, MD
- Recruiting
Hospital Universitario 12 Octubre
Madrid, Madrid
Enrique Gonzalez-Billalabeitia, MD
Enrique Gonzalez-Billalabeitia, MD
- Not yet recruiting
Hospital Universitario Clínico San Carlos
Madrid, Madrid
Natalia Vidal, MD
Natalia Vidal, MD
- Not yet recruiting
Hospital Universitario La Paz
Madrid, Madrid
Alvaro Pinto, MD
Alvaro Pinto, MD
- Not yet recruiting
Hospital Universitario Ramón y Cajal
Madrid, Madrid
Teresa Alonso, MD
Teresa Alonso, MD
- Not yet recruiting
Hospital Universitario Virgen de la Victoria
Málaga, Málaga
Bernardo Herrera, MD
Bernardo Herrera, MD
- Not yet recruiting
Hospital General Universitario Morales Meseguer
Murcia, Murcia
Antonio Rosino, MD
Antonio Rosino, MD
- Not yet recruiting
Hospital Universitario Marques de Valdecilla
Santander, Cantabria
Juan Diego Cacho, MD
Juan Diego Cacho, MD
- Not yet recruiting
Hospital Clínico Universitario Santiago de Compostela
Santiago de Compostela, La Coruña
Urbano Anido, MD
Urbano Anido, MD
- Not yet recruiting
Hospital Universitario Virgen Macarena
Seville, Sevilla
Alberto Torres, MD
Alberto Torres, MD
- Not yet recruiting
Fundación Instituto Valenciano de Oncología
Valencia, Valencia
David Llorente, MD
David Llorente, MD
- Not yet recruiting
Hospital Clinico Universitario de Valencia
Valencia, Valencia
Isabel Chirivella, MD
Isabel Chirivella, MD
- Not yet recruiting
Hospital General Universitario de Valencia
Valencia, Valencia
Cristina Caballero, MD
Cristina Caballero, MD
- Not yet recruiting
Hospital Clínico Universitario de Valladolid
Valladolid, Valladolid
Ricardo Sánchez- Escribano, MD
Ricardo Sánchez- Escribano, MD
- Not yet recruiting
Hospital Universitario Miguel Servet
Zaragoza, Aragon
Carmen Santander, MD
Carmen Santander, MD
France20 sites, 20 recruiting
- Not yet recruiting
CH Bayonne
Bayonne
Louis Francois, MD
Louis Francois, MD
- Not yet recruiting
Institut Bergonié
Bordeaux
Guilhem Roubaud, MD
Guilhem Roubaud, MD
- Not yet recruiting
CHP Brest - Pasteur
Brest
Ali Hasbini, MD
Ali Hasbini, MD
- Not yet recruiting
Hôpital Henri-Mondor
Créteil
Alexandre Ingels, MD
Alexandre Ingels, MD
- Not yet recruiting
GHM Cancérologie - Institut Daniel Hollard
Grenoble
Valentine Ruste, MD
Valentine Ruste, MD
- Not yet recruiting
Hôpital Franco-Britannique
Levallois-Perret
Caroline Pettenati, MD
Caroline Pettenati, MD
- Not yet recruiting
GHBS - Hôpital du Scorff
Lorient
Marie L'Huissier, MD
Marie L'Huissier, MD
- Not yet recruiting
Centre De Cancérologie Du Grand Montpellier
Montpellier
Emmanuel Nicolas, MD
Emmanuel Nicolas, MD
- Not yet recruiting
Institut du Cancer de Montpellier - Val d'Aurelle (ICM)
Montpellier
Diego Tosi, MD
Diego Tosi, MD
- Not yet recruiting
CHU Nîmes
Nîmes
Nadine Houede, MD
Nadine Houede, MD
- Not yet recruiting
Hospices Civils de Lyon - HCL
Paris
Denis Maillet, MD
Denis Maillet, MD
- Not yet recruiting
Hôpital Européen Georges Pompidou
Paris
Charles Dariane, MD
Charles Dariane, MD
- Not yet recruiting
Hôpital Paris Saint-Joseph
Paris
Carole Helissey, MD
Carole Helissey, MD
- Not yet recruiting
Hôpital Pitié-Salpêtrière
Paris
Paul Gougis, MD
Paul Gougis, MD
- Not yet recruiting
CHU Poitiers
Poitiers
Sheik Emambux, MD
Sheik Emambux, MD
- Not yet recruiting
Institut Godinot
Reims
Jean-Christophe Eymard, MD
Jean-Christophe Eymard, MD
- Not yet recruiting
CHU de Rennes
Rennes
Romain Mathieu, MD
Romain Mathieu, MD
- Not yet recruiting
Polyclinique Saint Georges
Saint-Georges-de-Didonne
Nice Ophélie Cassuto, MD
Nice Ophélie Cassuto, MD
- Not yet recruiting
CHP Saint Gregoire
Saint-Grégoire
Aurelien Gobert, MD
Aurelien Gobert, MD
- Not yet recruiting
Hôpital Foch
Suresnes
Yann Vano, MD
Yann Vano, MD
Germany9 sites, 9 recruiting
- Not yet recruiting
Facharztzentrum für Urologie, Uro-Onkologie
Berlin
Andreas Haßler, MD
Andreas Haßler, MD
- Not yet recruiting
Praxis Berlin / FASANUS - Urologie - Andrologie - Uro-Onkologie
Berlin
Andreas Maxeiner, MD
Andreas Maxeiner, MD
- Not yet recruiting
Johanniter-Krankenhaus Bonn-Gronau
Bonn
Carsten Ohlmann, MD
Carsten Ohlmann, MD
- Not yet recruiting
SRH Wald-Klinikum Gera
Gera
Susan Foller, MD
Susan Foller, MD
- Not yet recruiting
University Hospital Göttingen
Göttingen
Arne Strauß, MD
Arne Strauß, MD
- Not yet recruiting
Urologische Facharztpraxis Saale
Halle
Sandra Seseke, MD
Sandra Seseke, MD
- Not yet recruiting
Urologicum Karlsruhe MVZ
Karlsruhe
Christoph Vierneisel, MD
Christoph Vierneisel, MD
- Not yet recruiting
Klinikum Recklinghausen
Recklinghausen
Marco Brock, MD
Marco Brock, MD
- Not yet recruiting
University Hospital Rostock
Rostock
Angelika Borkowetz, MD
Angelika Borkowetz, MD
Italy5 sites, 5 recruiting
- Not yet recruiting
ARNAS Garibaldi - Catania
Catania
Roberto Bordonaro, MD
Roberto Bordonaro, MD
- Not yet recruiting
Hospital Riuniti di Foggia - Foggia
Foggia
Vincenza Conteduca, MD
Vincenza Conteduca, MD
- Not yet recruiting
National Instute of Oncology - Milan
Milan
Giuseppe Procopio, MD
Giuseppe Procopio, MD
- Not yet recruiting
Policlinico Gemelli Hospital - Rome
Roma
Roberto lacovelli, MD
Roberto Iacovelli, MD
- Not yet recruiting
Policlinico Umberto I - Rome
Roma
Daniele Santini, MD
Daniele Santini, MD
Portugal1 site, 1 recruiting
- Not yet recruiting
ULS Alto Ave
Guimarães
Carolina Carvalho, MD
Carolina Carvalho, MD
About this study
This is a phase III, randomized, open-label, multi-center study to assess the efficacy of treatment intensification with docetaxel plus apalutamide and ADT, assessed by event-free survival, in patients with mHSPC who do not achieve deep PSA response (≤0,2 ng/ml or PSA90 response in combination with a PSA ≤ 4 ng/ml) after initial treatment with apalutamide and ADT. A non-deep PSA response is defined as PSA > 0.2 ng/ml in combination with a PSA response < 90%, or a PSA response ≥90% in combination with a PSA > 4 ng/ml.
Read the detailed description
Approximately 320 patients will be randomized in a 1:1 ratio to the treatments as specified below:
- Arm A (experimental arm): docetaxel (75 mg/m2 every three weeks), for 6 planned cycles, plus apalutamide and ADT (240 mg, oral single daily dose).
- Arm B (control arm): continuation of SOC treatment with apalutamide and ADT (240 mg, oral single daily dose).
Randomization will be stratified by 3 factors:
- Metastasis timing (synchronous vs metachronous)
- Visceral metastasis at diagnosis (yes vs no)
- PSA at study inclusion (≤ 4 ng/ml vs >4 ng/ml) An IDMC will be established for regular safety monitoring, for the pre-planned interim analysis and the PK sub-study when available. The composition, role, responsibilities and procedures of the IDMC will be detailed in the IDMC Charter.
- Being tested
- Apalutamide (Erleada™) 60 mg or 240 mg tablets, Docetaxel
- Keywords
- Prostate Cancer, Apalutamide, Hormone-sensitive prostate cancer, Deep PSA response
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Apalutamide (Erleada™) 60 mg or 240 mg tabletsDrug
The dose of 240 mg (four 60 mg tablets or one single 240 mg tablet) daily of apalutamide is the recommended dose in the SmPC.
ADT will be chosen and administered according to standard clinical practice at each participating site and has not been included in the table below.
DocetaxelDrug
The recommended dose of docetaxel is 75 mg/m2 day 1 every 21 days. Six cycles of docetaxel will be administered.
| Study group | Role | What they receive |
|---|---|---|
| Arm A (experimental arm) | Experimental | Docetaxel (75 mg/m2 every three weeks), for 6 planned cycles, plus apalutamide (240 mg, oral single daily dose) and ADT. Receives: Drug: Apalutamide (Erleada™) 60 mg or 240 mg tablets; Drug: Docetaxel |
| Arm B (control arm) | No intervention | Continuation of SOC treatment with apalutamide (240 mg, oral single daily dose) and ADT. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Event-free Survival (EFS)
Event-free survival is defined as the time from randomization to occurrence of the following events, whichever occurs first in each treatment arm: PSA progression or radiographic progression of soft-tissue, visceral, or bone lesions or death from any cause.
Measured: 48 months
Secondary outcomes (16)
Time to castration resistance
Time to castration resistance is defined as time from randomization to radiographic disease progression, PSA progression per PCWG3 criteria, or symptomatic skeletal event (defined as radiation to bone, pathologic fracture, spinal cord compression, or surgery to bone due to symptoms), whichever occurred first in each treatment arm.
Measured: 48 months
Radiographic progression-free survival (rPFS)
Radiographic Progression-Free Survival is defined as the time from randomization to the first documented evidence of radiographic disease progression, as assessed by the investigator per Prostate Cancer Working Group 3 (PCWG3) criteria for bone lesions and RECIST v1.1 for soft tissue lesions, or death from any cause, whichever occurs first in each treatment arm.
Measured: 48 months
PSA progression-free survival
PSA progression-free survival (PSA-PFS) is defined according to PCWG3 criteria as the time from randomization to the date of PSA progression (a ≥25% increase and an absolute increase of ≥2 ng/mL from nadir, confirmed by a second value ≥3 weeks later) or death from any cause, whichever occurs first in each treatment arm.
Measured: 48 months
Overall survival
Overall survival is defined as time from randomization to date of death from any cause in each treatment arm.
Measured: 48 months
Time to subsequent treatment
Time to subsequent treatment is defined as the time from randomization to the initiation of the first subsequent systemic anticancer therapy after study drugs discontinuation, or death, whichever occurs first in each treatment arm.
Measured: 48 months
Deep PSA response rate at 6 months in each treatment arm.
Deep PSA response is defined as achieving a prostate-specific antigen (PSA) level ≤0.2 ng/mL or PSA Response ≥90% in combination with a PSA ≤ 4 ng/ml.
Measured: 6 months
Ultradeep PSA response rate at 6 months in each treatment arm.
Ultradeep PSA response 1 is defined as achieving a prostate-specific antigen (PSA) level between 0.2 and 0.02 ng/mL.
Ultradeep PSA response 2 is defined as achieving a prostate-specific antigen (PSA) level ≤ 0.02 ng/mL.
Measured: 6 months
Symptomatic skeletal event-free survival
Symptomatic skeletal event-free survival (SSE-FS) is defined as the time from randomization to the first occurrence of a symptomatic skeletal event (defined as radiation to bone, pathologic fracture, spinal cord compression, or surgery to bone due to symptoms) or death from any cause, whichever occurred first in each treatment arm.
Measured: 48 months
To evaluate the safety profile of treatment intensification with docetaxel plus apalutamide and ADT (Adverse events)
Percentage of patients with at least one adverse event. Toxicity profile will be assessed using the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE), version 5.0. Patients with each adverse event will be calculated over the total number of patients exposed in each treatment arm.
Measured: 25 months
Time to initiate opioid use (≥ 7 days)
Time to initiate opioid use (≥ 7 days) is defined as the time from randomization to the first initiation of opioid analgesic use lasting for 7 or more consecutive days, regardless of the reason, or until death, whichever occurs first in each treatment arm.
Measured: 48 months
To evaluate the safety profile of treatment intensification with docetaxel plus apalutamide and ADT (Serious adverse events).
Patients with at least a serious adverse event will be calculated over the total number of patients exposed in each treatment arm.
Measured: 25 months
To evaluate the safety profile of treatment intensification with docetaxel plus apalutamide and ADT (Adverse events leading to treatment discontinuation ).
Patients with at least an adverse event leading to treatment discontinuation and adverse events leading to death will be calculated over the total number of patients exposed in each treatment arm.
Measured: 25 months
To evaluate the safety profile of treatment intensification with docetaxel plus apalutamide and ADT (Death)
Dead patients calculated over the total number of patients exposed in each treatment arm.
Measured: 25 months
To assess the quality of life of patients with FACT-P subscale
Change from baseline over time in FACT-P subscale in each treatment arm.
Measured: 24 months
To assess the quality of life of patients with BPI-SF interference subscale
Change from baseline over time in BPI-SF interference subscale in each treatment arm.
Measured: 24 months
To assess the quality of life of patients with BPI-SF interference subscale.
Change from baseline over time in BFI subscale in each treatment arm.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jan 2026
- Study start5 Jun 2026
- Primary completion31 Mar 2030 (estimated)
- Study completion31 Mar 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Hormone-sensitive Prostate CancerStudies of the same condition, open and under way.
- 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
- 320 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Alianza multidisciplinar para la investigación de los tumores genitourinarios -GUARD
- Sponsor type
- University, hospital or other
- Collaborators
- Apices Soluciones S.L.
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07333066
- Sponsor's protocol ID
- REINFORCE
- Other IDs
- 2025-524408-30-00, 2025
- Acronym
- REINFORCE
- Status last verified
- Jun 2026
- First submitted
- 30 Dec 2025
- Last updated
- 17 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase III Randomized International Open Label Clinical Trial of Treatment Intensification With Docetaxel Plus Apalutamide in Patients With Metastatic Hormone-sensitive Prostate Cancer Who Did Not Achieve a Deep PSA Response After Initial Treatment With Apalutamide: REINFORCE Trial.
- ClinicalTrials.gov ID
- NCT07333066
- Acronym / sponsor ID
- REINFORCE / REINFORCE
- Keywords
- Prostate Cancer, Apalutamide, Hormone-sensitive prostate cancer, Deep PSA response
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 320 participants (estimated)
- Lead sponsor
- Alianza multidisciplinar para la investigación de los tumores genitourinarios -GUARDUniversity, hospital or other
- Collaborators
- Apices Soluciones S.L.
- Study start
- 5 Jun 2026 (actual)
- Primary completion
- 31 Mar 2030 (estimated)
- Study completion
- 31 Mar 2030 (estimated)
- First posted
- 12 Jan 2026 (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 is a phase III, randomized, open-label, multi-center study to assess the efficacy of treatment intensification with docetaxel plus apalutamide and ADT, assessed by event-free survival, in patients with mHSPC who do not achieve deep PSA response (≤0,2 ng/ml or PSA90 response in combination with a PSA ≤ 4 ng/ml) after initial treatment with apalutamide and ADT. A non-deep PSA response is defined as PSA > 0.2 ng/ml in combination with a PSA response < 90%, or a PSA response ≥90% in combination with a PSA > 4 ng/ml.
Detailed description
Approximately 320 patients will be randomized in a 1:1 ratio to the treatments as specified below:
- Arm A (experimental arm): docetaxel (75 mg/m2 every three weeks), for 6 planned cycles, plus apalutamide and ADT (240 mg, oral single daily dose).
- Arm B (control arm): continuation of SOC treatment with apalutamide and ADT (240 mg, oral single daily dose).
Randomization will be stratified by 3 factors:
- Metastasis timing (synchronous vs metachronous)
- Visceral metastasis at diagnosis (yes vs no)
- PSA at study inclusion (≤ 4 ng/ml vs >4 ng/ml) An IDMC will be established for regular safety monitoring, for the pre-planned interim analysis and the PK sub-study when available. The composition, role, responsibilities and procedures of the IDMC will be detailed in the IDMC Charter.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A (experimental arm) | Experimental | Drug: Apalutamide (Erleada™) 60 mg or 240 mg tablets, Drug: DocetaxelDocetaxel (75 mg/m2 every three weeks), for 6 planned cycles, plus apalutamide (240 mg, oral single daily dose) and ADT. |
| Arm B (control arm) | No intervention | –Continuation of SOC treatment with apalutamide (240 mg, oral single daily dose) and ADT. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Written informed consent. Each patient must sign an informed consent form (ICF) indicating that he understands the purpose of and procedures, required for the study, and is willing to participate in the study.
- Patient must be a man ≥18 years of age.
- Histologically or cytologically confirmed adenocarcinoma of prostate.
- Metastatic hormone-sensitive prostate cancer.
- PSA >5 ng/ml at diagnosis of metastatic disease.
Key exclusion criteria (24 listed)
- Presence of neuroendocrine histology.
- Apalutamide treatment started more than 30 weeks before inclusion.
- Progression disease by any means, including radiographic, clinical or serological at inclusion.
- Patient who achieves deep PSA response on apalutamide treatment before randomization.
- Previous androgen-pathway receptor inhibitors, including enzalutamide, darolutamide, abiraterone or other ARPI. Previous treatment with first generation antiandrogens (i.e. bicalutamide) is allowed.
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 |
|---|---|---|
| Apalutamide (Erleada™) 60 mg or 240 mg tabletsThe dose of 240 mg (four 60 mg tablets or one single 240 mg tablet) daily of apalutamide is the recommended dose in the SmPC. ADT will be chosen and administered according to standard clinical practice at each participating site and has not been included in the table below. | Drug | Arm A (experimental arm) |
| DocetaxelThe recommended dose of docetaxel is 75 mg/m2 day 1 every 21 days. Six cycles of docetaxel will be administered. | Drug | Arm A (experimental arm) |
Primary outcome
Event-free Survival (EFS)
Time frame: 48 months
Event-free survival is defined as the time from randomization to occurrence of the following events, whichever occurs first in each treatment arm: PSA progression or radiographic progression of soft-tissue, visceral, or bone lesions or death from any cause.
16 secondary outcomes
Time to castration resistance
Time frame: 48 months
Radiographic progression-free survival (rPFS)
Time frame: 48 months
PSA progression-free survival
Time frame: 48 months
Overall survival
Time frame: 48 months
Time to subsequent treatment
Time frame: 48 months
Deep PSA response rate at 6 months in each treatment arm.
Time frame: 6 months
Ultradeep PSA response rate at 6 months in each treatment arm.
Time frame: 6 months
Symptomatic skeletal event-free survival
Time frame: 48 months
To evaluate the safety profile of treatment intensification with docetaxel plus apalutamide and ADT (Adverse events)
Time frame: 25 months
Time to initiate opioid use (≥ 7 days)
Time frame: 48 months
To evaluate the safety profile of treatment intensification with docetaxel plus apalutamide and ADT (Serious adverse events).
Time frame: 25 months
To evaluate the safety profile of treatment intensification with docetaxel plus apalutamide and ADT (Adverse events leading to treatment discontinuation ).
Time frame: 25 months
To evaluate the safety profile of treatment intensification with docetaxel plus apalutamide and ADT (Death)
Time frame: 25 months
To assess the quality of life of patients with FACT-P subscale
Time frame: 24 months
To assess the quality of life of patients with BPI-SF interference subscale
Time frame: 24 months
To assess the quality of life of patients with BPI-SF interference subscale.
Time frame: 24 months
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 17 Jun 2026.
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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.
56 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Apalutamide (Erleada™) 60 mg or 240 mg tablets and Docetaxel in people with Metastatic Hormone-sensitive Prostate Cancer, run by Alianza multidisciplinar para la investigación de los tumores genitourinarios -GUARD at 56 sites in 5 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 21 inclusion and 24 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 17 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 56 sites in Spain, France, Germany, Italy, Portugal. 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 GUARD (+34 93 452 79 18, info@guardconsortium.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Event-free Survival (EFS) (time frame: 48 months). 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 17 Jun 2026.