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.

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. 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.

11. 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)

12. Peripheral neuropathy ≥ grade 2.

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

14. 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.

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

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

17. 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.

18. 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.

What this study is about