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.

NCT ID: NCT07333066

Last Updated: 2026-01-12

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 320 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-03-31
• Study Completion Date: 2030-03-31

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.

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.

Conditions

Metastatic Hormone-sensitive Prostate Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A (experimental arm)

Docetaxel (75 mg/m2 every three weeks), for 6 planned cycles, plus apalutamide (240 mg, oral single daily dose) and ADT.

Group Type: EXPERIMENTAL

Apalutamide (Erleada™) 60 mg or 240 mg tablets

Intervention Type: 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.

Docetaxel

Intervention Type: DRUG

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

Arm B (control arm)

Continuation of SOC treatment with apalutamide (240 mg, oral single daily dose) and ADT.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Apalutamide (Erleada™) 60 mg or 240 mg tablets

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.

Intervention Type: DRUG

Docetaxel

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. 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.

2. Patient must be a man ≥18 years of age.

3. Histologically or cytologically confirmed adenocarcinoma of prostate.

4. Metastatic hormone-sensitive prostate cancer.

5. PSA >5 ng/ml at diagnosis of metastatic disease.

6. Patients eligible to continue treatment with apalutamide and ADT and without contra-indication to receive docetaxel.

7. Patients with at least 24 weeks and no more than 30 weeks of apalutamide.

8. Patients with a maximum of 12 weeks ADT before apalutamide initiation.

9. 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.

10. Patients who have not progressed to apalutamide.

11. Patients that are tolerating adequately apalutamide 240 mg daily and with no toxicity higher than G1 at inclusion.

12. Be able to swallow whole apalutamide film-coated tablets.

13. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.

14. Clinical laboratory values at screening:

1. hemoglobin ≥10.0 g/dL,

2. absolute neutrophil count ≥1.5 × 10*9/L,

3. 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

4. serum alanine aminotransferase and/or aspartate transaminase ≤1.5 × the upper limit of normal (ULN),

5. total bilirubin ≤ ULN,

6. creatinine ≤2.0 × ULN

15. 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.

Exclusion Criteria

1. Presence of neuroendocrine histology.

2. Apalutamide treatment started more than 30 weeks before inclusion.

3. Progression disease by any means, including radiographic, clinical or serological at inclusion.

4. Patient who achieves deep PSA response on apalutamide treatment before randomization.

5. Previous androgen-pathway receptor inhibitors, including enzalutamide, darolutamide, abiraterone or other ARPI. Previous treatment with first generation antiandrogens (i.e. bicalutamide) is allowed.

6. Chemotherapy or immunotherapy for prostate cancer before randomization.

7. Treatment with radiotherapy (external-beam radiation therapy, brachytherapy, or radiopharmaceuticals) within 2 weeks before randomization.

8. Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation of the study drugs.

9. Contraindication to both computed tomography and magnetic resonance imaging contrast agent.

10. Any of the following within 6 months before randomization:

1. stroke,

2. myocardial infarction,

3. severe or unstable angina pectoris,

4. uncontrolled arrhythmia,

5. coronary or peripheral artery bypass graft, or

6. congestive heart failure (New York Heart Association class III or IV)

11. Peripheral neuropathy ≥ grade 2.

12. Uncontrolled hypertension, indicated by resting systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg despite medical management.

13. 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.

14. A gastrointestinal disorder or procedure that was expected to interfere significantly with absorption of study drug.

15. Active viral hepatitis, known human immunodeficiency virus infection with detectable viral load, or chronic liver disease requiring treatment.

16. 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.

17. 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Apices Soluciones S.L.

INDUSTRY

Sponsor Role: collaborator

Alianza multidisciplinar para la investigación de los tumores genitourinarios -GUARD

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

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

Countries

France; Germany; Italy; Portugal; Spain

Central Contacts

GUARD

Role: CONTACT

info@guardconsortium.org

+34 93 452 79 18

Facility Contacts

Louis Francois, MD

Role: primary

Guilhem Roubaud, MD

Role: primary

Ali Hasbini, MD

Role: primary

Alexandre Ingels, MD

Role: primary

Valentine Ruste, MD

Role: primary

Caroline Pettenati, MD

Role: primary

Marie L'Huissier, MD

Role: primary

Emmanuel Nicolas, MD

Role: primary

Diego Tosi, MD

Role: primary

Nadine Houede, MD

Role: primary

Denis Maillet, MD

Role: primary

Charles Dariane, MD

Role: primary

Carole Helissey, MD

Role: primary

Paul Gougis, MD

Role: primary

Sheik Emambux, MD

Role: primary

Jean-Christophe Eymard, MD

Role: primary

Romain Mathieu, MD

Role: primary

Nice Ophélie Cassuto, MD

Role: primary

Aurelien Gobert, MD

Role: primary

Yann Vano, MD

Role: primary

Andreas Haßler, MD

Role: primary

Andreas Maxeiner, MD

Role: primary

Carsten Ohlmann, MD

Role: primary

Susan Foller, MD

Role: primary

Arne Strauß, MD

Role: primary

Sandra Seseke, MD

Role: primary

Christoph Vierneisel, MD

Role: primary

Marco Brock, MD

Role: primary

Angelika Borkowetz, MD

Role: primary

Roberto Bordonaro, MD

Role: primary

Vincenza Conteduca, MD

Role: primary

Giuseppe Procopio, MD

Role: primary

Roberto lacovelli, MD

Role: primary

Daniele Santini, MD

Role: primary

Carolina Carvalho, MD

Role: primary

Carmen Santander, MD

Role: primary

Dolores Fenor de la Maza, MD

Role: primary

Marta García de Herreros, MD

Role: primary

Alejo Rodríguez-Vida, MD

Role: primary

Mikel Portu, MD

Role: primary

Albert Font, MD

Role: primary

Jose María Piulats, MD

Role: primary

Juan Diego Cacho, MD

Role: primary

Raquel Luque, MD

Role: primary

Urbano Anido, MD

Role: primary

Enrique Gonzalez-Billalabeitia, MD

Role: primary

Natalia Vidal, MD

Role: primary

Alvaro Pinto, MD

Role: primary

Teresa Alonso, MD

Role: primary

Antonio Rosino, MD

Role: primary

Bernardo Herrera, MD

Role: primary

Alberto Torres, MD

Role: primary

David Llorente, MD

Role: primary

Isabel Chirivella, MD

Role: primary

Cristina Caballero, MD

Role: primary

Ricardo Sánchez- Escribano, MD

Role: primary

Other Identifiers

2025-524408-30-00

Identifier Type: CTIS

Identifier Source: secondary_id

REINFORCE

Identifier Type: -

Identifier Source: org_study_id