This is a multi-center phase III study to compare the clinical benefit of androgen deprivation therapy with or without docetaxel with or without local radiotherapy with or without abiraterone acetate and prednisone in patient with metastatic hormone-naïve prostate cancer.

Eligible patients can be randomize in the trial after his consent form has been signed, and after all inclusion and non-inclusion criteria have been checked.

The randomisation will result in the allocation of arm A (ADT +docetaxel), arm B (ADT +docetaxel +Abiraterone), arm C (ADT +docetaxel +radiotherapy) or arm D (ADT +docetaxel +Abiraterone +radiotherapy) in a 1:1:1:1 ratio.

The randomization will be stratified (by minimization) according to:

• enrolment center,
• performance status (0 vs. 1-2)
• disease extent: lymph nodes only vs. bone (with or without lymph nodes) vs. presence of visceral metastases.

CRPC is defined by cancer progression (either a confirmed PSA rise or a radiological progression) with serum testosterone being at castrated levels (<0.50 ng/mL).

When the CRPC stage is reached, castration (either LHRH agonist or LHRH antagonist) will be maintained in all patients.

Investigators will be free to manage patients reaching CRPC at their discretion (using for example docetaxel, zoledronic acid, denosumab, sipuleucel-T, radium-223, cabazitaxel, etc) according to local uses and guidelines.

Abiraterone may be used in arm A and C if abiraterone has become the standard treatment for CRPC when this stage is reached.

Inclusion criteria:

1. Histologically or cytologically confirmed adenocarcinoma of the prostate,

2. Metastatic disease documented by a positive bone scan (any technique) or CT scan or an MRI. For patients with nodal metastases only, only patients with extra-pelvic enlarged lymph nodes (lymph nodes located above the iliac bifurcation) can be included if they have either:

   o At least one extra-pelvic lymph node ≥ 2 cm or extra-pelvic lymph node (s) ≥ 1 cm if the patients also have at least one pelvic lymph node ≥ 2 cm

3. Patients with ECOG ≤ 1 (patient with PS 2 due to bone pain can be accrued in the trial),

4. Life expectancy of at least 6 months,

5. Male aged ≥ 18 years old and ≤ 80 years old ,

6. Hematology values:

   • Hemoglobin ≥ 10.0 g/dL,
   • Platelet count ≥ 100,000/mL,
   • Neutrophil ≥ 1500 cells/mm³

7. Biochemistry values:

   • Renal function: Serum creatinine < 1.5 x ULN or a calculated creatinine clearance ≥ 60 mL/min,

   • Serum potassium ≥ 4 mmol/L,

   • Liver function:

     • Serum bilirubin ≤ 1.5 x ULN (except for patients with documented Gilbert's disease),
     • AST and ALT ≤ 1.5 x ULN (and ≤ 5 ULN in case of liver metastases),

   • ALK-P ≤ 2.5 x ULN (in case of bone metastasis, ALK-P<1000U/L if bilirubin is normal)

8. Patients must have received ADT for a maximum of 3 months before randomization and there must be a minimum of 6 weeks between the start of ADT and the start of Docetaxel,

9. Patients willing and clinically fit to receive Docetaxel which is defined by the following :

   • Patients respecting all inclusion and exclusion criteria And
   • Patients with no contraindication to docetaxel according to the SmPC of the drug And
   • Patients presenting all medical requirements to receive docetaxel according to the investigator's opinion.

10. Patients might have received previous radiation therapy directed to bone lesions,

11. Patients able to take oral medication,

12. Patients who have received the information sheet and signed the informed consent form,

13. Male patients who will receive Docetaxel and/or Abiraterone acetate and have partners of childbearing potential and/or pregnant partners must use a method of birth control in addition to an adequate barrier protection (condoms) as determined to be acceptable by the study doctor during the treatment period and for 4 weeks after the last dose of abiraterone acetate and/or for 6 months after the last dose of Docetaxel

14. Patients must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures,

15. Patients with a public or a private health insurance coverage, according to local laws for participation in clinical trials.

Exclusion Criteria:

1. Patients with previous definitive local treatment directed to the prostate primary cancer (radiotherapy, brachytherapy, radical prostatectomy, ultrasound, cryotherapy, or other). A previous trans-urethral resection of the prostate (TURP) and previous local treatments of metastases are allowed,

2. Prior cytotoxic chemotherapy or biological therapy for the treatment of prostate cancer,

3. Any chronic medical condition requiring a higher dose of corticosteroid than 5 mg prednisone/prednisolone twice daily,

4. Active infection or other medical condition for which prednisone/prednisolone (corticosteroid) use would be contra-indicated,

5. Previously treated with ketoconazole for prostate cancer for more than 7 days,

6. Prior systemic treatment with an azole drug (e.g. fluconazole, itraconazole) within 4 weeks of randomization,

7. Hypertension not controlled by an anti-hypertensive treatment (systolic BP ≥ 160 mmHg or diastolic BP ≥ 95 mmHg; 3 consecutive measures taken 5 minutes apart),

8. Severe or moderate hepatic impairment (Child - Pugh class C or B)

9. Active or symptomatic viral hepatitis or chronic liver disease (except Gilbert's disease),

10. History of pituitary or adrenal dysfunction,

11. Clinically known significant heart disease in the past 6 months as evidenced by myocardial infarction, or arterial thrombotic events, severe or unstable angina, or New York Heart association (NYHA) Class II-IV heart disease or cardiac ejection fraction measurement of < 50% at baseline,

12. Atrial Fibrillation, or other cardiac arrhythmia requiring therapy,

13. Patient with unstable pulmonary disease (eg. Pulmonary embolism)

14. Pathological finding consistent with small cell carcinoma of the prostate,

15. History of malignancy, except non-melanoma skin cancer, with a ≥ 30% probability of recurrence within 24 months,

16. Known allergies, hypersensitivity or intolerance to the study drugs or excipients or docetaxel

17. Administration of an investigational therapeutic within 30 days of randomization,

18. Patients already included in another therapeutic trial involving an experimental drug (patient in a non-experimental trial with no modification of the patient's care can be included),

19. Patients with significantly altered mental status prohibiting the understanding of the study or with psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule or any condition which, in the opinion of the investigator, would preclude participation in this trial. Those conditions should be discussed with the patient before registration in the trial,

20. Individual deprived of liberty or placed under the authority of a tutor.

21. Patients with impaired vision should undergo a prompt and complete ophthalmologic examination.

    Patients with Cystoid Macular Oedema cannot be included due to a potential risk of deterioration associated with docetaxel.

22. Concomitant use of strong CYP3A4 inhibitors (clarithromycin, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin.)

Individual Participant Data will not be shared at an individual level. Those data will be part of the study database including all enrolled patients.