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.

NCT07333066 | Not Yet Recruiting Phase 3 DMC

• 2 other identifiers: REINFORCE2025-524408-30-00
• Study Type: interventional
• Target: 320
• Locations: 5 countries
• Sites: 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.

Conditions

Metastatic Hormone-sensitive Prostate Cancer

Keywords

Prostate Cancer; Apalutamide; Hormone-sensitive prostate cancer; Deep PSA response

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

Study Arms (2)

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.

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.

Interventions

Apalutamide (Erleada™) 60 mg or 240 mg tablets DRUG

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.

Arm A (experimental arm)

Docetaxel DRUG

The recommended dose of docetaxel is 75 mg/m2 day 1 every 21 days. Six cycles of docetaxel will be administered.

Arm A (experimental arm)

Eligibility Criteria

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

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,

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.
• 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.

Sponsors & Collaborators

• Apices Soluciones S.L.: collaborator
• Alianza multidisciplinar para la investigación de los tumores genitourinarios -GUARD: lead

Study Sites (56)

CH Bayonne

Bayonne, France

Location

Institut Bergonié

Bordeaux, France

Location

CHP Brest - Pasteur

Brest, France

Location

Hôpital Henri-Mondor

Créteil, France

Location

GHM Cancérologie - Institut Daniel Hollard

Grenoble, France

Location

Hôpital Franco-Britannique

Levallois-Perret, France

Location

GHBS - Hôpital du Scorff

Lorient, France

Location

Centre De Cancérologie Du Grand Montpellier

Montpellier, France

Location

Institut du Cancer de Montpellier - Val d'Aurelle (ICM)

Montpellier, France

Location

CHU Nîmes

Nîmes, France

Location

Hospices Civils de Lyon - HCL

Paris, France

Location

Hôpital Européen Georges Pompidou

Paris, France

Location

Hôpital Paris Saint-Joseph

Paris, France

Location

Hôpital Pitié-Salpêtrière

Paris, France

Location

CHU Poitiers

Poitiers, France

Location

Institut Godinot

Reims, France

Location

CHU de Rennes

Rennes, France

Location

Polyclinique Saint Georges

Saint-Georges-de-Didonne, France

Location

CHP Saint Gregoire

Saint-Grégoire, France

Location

Hôpital Foch

Suresnes, France

Location

Facharztzentrum für Urologie, Uro-Onkologie

Berlin, Germany

Location

Praxis Berlin / FASANUS - Urologie - Andrologie - Uro-Onkologie

Berlin, Germany

Location

Johanniter-Krankenhaus Bonn-Gronau

Bonn, Germany

Location

SRH Wald-Klinikum Gera

Gera, Germany

Location

University Hospital Göttingen

Göttingen, Germany

Location

Urologische Facharztpraxis Saale

Halle, Germany

Location

Urologicum Karlsruhe MVZ

Karlsruhe, Germany

Location

Klinikum Recklinghausen

Recklinghausen, Germany

Location

University Hospital Rostock

Rostock, Germany

Location

ARNAS Garibaldi - Catania

Catania, Italy

Location

Hospital Riuniti di Foggia - Foggia

Foggia, Italy

Location

National Instute of Oncology - Milan

Milan, Italy

Location

Policlinico Gemelli Hospital - Rome

Roma, Italy

Location

Policlinico Umberto I - Rome

Roma, Italy

Location

ULS Alto Ave

Guimarães, Portugal

Location

Hospital Universitario Miguel Servet

Zaragoza, Aragon, Spain

Location

Hospital Universitari Vall d´Hebron

Barcelona, Bacelona, Spain

Location

Hospital Clínic de Barcelona

Barcelona, Barcelona, Spain

Location

Hospital del Mar

Barcelona, Barcelona, Spain

Location

Hospital Santa Creu i Sant Pau

Barcelona, Barcelona, Spain

Location

ICO Badalona

Barcelona, Barcelona, Spain

Location

Institut Català d'Oncologia (ICO) L´Hospitalet de Llobregat

L'Hospitalet de Llobregat, Barcelona, Spain

Location

Hospital Universitario Marques de Valdecilla

Santander, Cantabria, Spain

Location

Hospital Universitario Virgen de las Nieves

Granada, Granada, Spain

Location

Hospital Clínico Universitario Santiago de Compostela

Santiago de Compostela, La Coruña, Spain

Location

Hospital Universitario 12 Octubre

Madrid, Madrid, Spain

Location

Hospital Universitario Clínico San Carlos

Madrid, Madrid, Spain

Location

Hospital Universitario La Paz

Madrid, Madrid, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, Madrid, Spain

Location

Hospital General Universitario Morales Meseguer

Murcia, Murcia, Spain

Location

Hospital Universitario Virgen de la Victoria

Málaga, Málaga, Spain

Location

Hospital Universitario Virgen Macarena

Seville, Sevilla, Spain

Location

Fundación Instituto Valenciano de Oncología

Valencia, Valencia, Spain

Location

Hospital Clinico Universitario de Valencia

Valencia, Valencia, Spain

Location

Hospital General Universitario de Valencia

Valencia, Valencia, Spain

Location

Hospital Clínico Universitario de Valladolid

Valladolid, Valladolid, Spain

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

apalutamide; Docetaxel

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Central Study Contacts

GUARD

CONTACT

+34 93 452 79 18; info@guardconsortium.org

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: March 31, 2026
• Primary Completion (Estimated): March 31, 2030
• Study Completion (Estimated): March 31, 2030
• Last Updated: January 12, 2026

Record last verified: 2025-12

Locations

PT (1); ES (21); FR (20); DE (9); IT (5)