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.

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.