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.
REINFORCE
2 other identifiers
interventional
320
5 countries
56
Brief 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) 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Jun 2026
Typical duration for phase_3
56 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 30, 2025
CompletedFirst Posted
Study publicly available on registry
January 12, 2026
CompletedStudy Start
First participant enrolled
June 5, 2026
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 31, 2030
ExpectedStudy Completion
Last participant's last visit for all outcomes
March 31, 2030
June 17, 2026
June 1, 2026
3.8 years
December 30, 2025
June 15, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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.
48 months
Secondary Outcomes (16)
Time to castration resistance
48 months
Radiographic progression-free survival (rPFS)
48 months
PSA progression-free survival
48 months
Overall survival
48 months
Time to subsequent treatment
48 months
- +11 more secondary outcomes
Study Arms (2)
Arm A (experimental arm)
EXPERIMENTALDocetaxel (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 INTERVENTIONContinuation of SOC treatment with apalutamide (240 mg, oral single daily dose) and ADT.
Interventions
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.
The recommended dose of docetaxel is 75 mg/m2 day 1 every 21 days. Six cycles of docetaxel will be administered.
Eligibility Criteria
You may qualify if:
- 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.
- 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.
- 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,
- +5 more criteria
You may not qualify if:
- Presence of neuroendocrine histology.
- 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.
- 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)
- +7 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (56)
CH Bayonne
Bayonne, France
Institut Bergonié
Bordeaux, France
CHP Brest - Pasteur
Brest, France
Hôpital Henri-Mondor
Créteil, France
GHM Cancérologie - Institut Daniel Hollard
Grenoble, France
Hôpital Franco-Britannique
Levallois-Perret, France
GHBS - Hôpital du Scorff
Lorient, France
Centre De Cancérologie Du Grand Montpellier
Montpellier, France
Institut du Cancer de Montpellier - Val d'Aurelle (ICM)
Montpellier, France
CHU Nîmes
Nîmes, France
Hospices Civils de Lyon - HCL
Paris, France
Hôpital Européen Georges Pompidou
Paris, France
Hôpital Paris Saint-Joseph
Paris, France
Hôpital Pitié-Salpêtrière
Paris, France
CHU Poitiers
Poitiers, France
Institut Godinot
Reims, France
CHU de Rennes
Rennes, France
Polyclinique Saint Georges
Saint-Georges-de-Didonne, France
CHP Saint Gregoire
Saint-Grégoire, France
Hôpital Foch
Suresnes, France
Facharztzentrum für Urologie, Uro-Onkologie
Berlin, Germany
Praxis Berlin / FASANUS - Urologie - Andrologie - Uro-Onkologie
Berlin, Germany
Johanniter-Krankenhaus Bonn-Gronau
Bonn, Germany
SRH Wald-Klinikum Gera
Gera, Germany
University Hospital Göttingen
Göttingen, Germany
Urologische Facharztpraxis Saale
Halle, Germany
Urologicum Karlsruhe MVZ
Karlsruhe, Germany
Klinikum Recklinghausen
Recklinghausen, Germany
University Hospital Rostock
Rostock, Germany
ARNAS Garibaldi - Catania
Catania, Italy
Hospital Riuniti di Foggia - Foggia
Foggia, Italy
National Instute of Oncology - Milan
Milan, Italy
Policlinico Gemelli Hospital - Rome
Roma, Italy
Policlinico Umberto I - Rome
Roma, Italy
ULS Alto Ave
Guimarães, Portugal
Hospital Universitario Miguel Servet
Zaragoza, Aragon, Spain
Hospital Universitari Vall d´Hebron
Barcelona, Bacelona, Spain
Hospital Clínic de Barcelona
Barcelona, Barcelona, Spain
Hospital del Mar
Barcelona, Barcelona, Spain
Hospital Santa Creu i Sant Pau
Barcelona, Barcelona, Spain
ICO Badalona
Barcelona, Barcelona, Spain
Institut Català d'Oncologia (ICO) L´Hospitalet de Llobregat
L'Hospitalet de Llobregat, Barcelona, Spain
Hospital Universitario Marques de Valdecilla
Santander, Cantabria, Spain
Hospital Universitario Virgen de las Nieves
Granada, Granada, Spain
Hospital Clínico Universitario Santiago de Compostela
Santiago de Compostela, La Coruña, Spain
Hospital Universitario 12 Octubre
Madrid, Madrid, Spain
Hospital Universitario Clínico San Carlos
Madrid, Madrid, Spain
Hospital Universitario La Paz
Madrid, Madrid, Spain
Hospital Universitario Ramón y Cajal
Madrid, Madrid, Spain
Hospital General Universitario Morales Meseguer
Murcia, Murcia, Spain
Hospital Universitario Virgen de la Victoria
Málaga, Málaga, Spain
Hospital Universitario Virgen Macarena
Seville, Sevilla, Spain
Fundación Instituto Valenciano de Oncología
Valencia, Valencia, Spain
Hospital Clinico Universitario de Valencia
Valencia, Valencia, Spain
Hospital General Universitario de Valencia
Valencia, Valencia, Spain
Hospital Clínico Universitario de Valladolid
Valladolid, Valladolid, Spain
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 30, 2025
First Posted
January 12, 2026
Study Start
June 5, 2026
Primary Completion (Estimated)
March 31, 2030
Study Completion (Estimated)
March 31, 2030
Last Updated
June 17, 2026
Record last verified: 2026-06