Please select the eligibility criteria that correspond to the clinical trial below.
Title: PREVAIL: A MULTINATIONAL PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED EFFICACY AND SAFETY STUDY OF ORAL MDV3100 IN CHEMOTHERAPY-NAÏVE PATIENTS WITH PROGRESSIVE METASTATIC PROSTATE CANCER WHO HAVE FAILED ANDROGEN DEPRIVATION THERAPY
Brief Summary: The purpose of this study is to determine the benefit of enzalutamide versus placebo as assessed by overall survival and progression-free survival in patients with progressive metastatic prostate cancer who have failed androgen deprivation therapy but not yet received chemotherapy.


Options:
A: Inclusion Criteria:

* Newly diagnosed metastatic prostate cancer within 3 months prior to randomization with histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell histology
* Distant metastatic disease documented by positive bone scan or metastatic lesions on computed tomography (CT) or magnetic resonance imaging (MRI) scan
* At least 2 of the following high-risk prognostic factors: Gleason score of greater than or equal to (\>=8); presence of 3 or more lesions on bone scan; presence of measurable visceral (excluding lymph node disease) metastasis on CT or MRI Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 scan
* Eastern Cooperative Oncology Group (ECOG) performance status grade of 0, 1 or 2
* Adequate hematologic, hepatic, and renal function
* Agrees to protocol-defined use of effective contraception

Exclusion Criteria:

* Active infection or other medical condition that would make prednisone use contraindicated
* Any chronic medical condition requiring a higher systemic dose of corticosteroid than 5 mg prednisone per day
* Pathological finding consistent with small cell carcinoma of the prostate
* Known brain metastasis
* Any prior pharmacotherapy, radiation therapy, or surgery for metastatic prostate cancer (the following exception are permitted): up to 3 months of androgen deprivation therapy (ADT) with lutenizing hormone releasing hormone agonists or antagonists or orchiectomy with or without concurrent anti-androgens prior Cycle 1 Day 1; participants may have one course of palliative radiation or surgical therapy to treat symptoms resulting from metastatic disease if it was administered at least 28 days prior to Cycle 1 Day 1)
B: Randomized, Double Blind Treatment Period:

Inclusion Criteria:

* Histologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features
* Ongoing androgen deprivation therapy with a GnRH analogue or bilateral orchiectomy
* Progressive disease despite androgen deprivation therapy as defined by rising PSA levels or progressive soft tissue or bony disease
* No prior treatment with cytotoxic chemotherapy
* Asymptomatic or mildly symptomatic from prostate cancer

Exclusion Criteria:

* Severe concurrent disease, infection, or co-morbidity that, in the judgment of the Investigator, would make the patient inappropriate for enrollment
* Known or suspected brain metastasis or active leptomeningeal disease
* History of another malignancy within the previous 5 years other than curatively treated non-melanomatous skin cancer

Open-Label Treatment Period:

The following inclusion criteria apply to patients receiving enzalutamide or placebo during double-blind treatment.

Eligible patients must meet all inclusion criteria.

* Received randomized double-blind treatment in PREVAIL;
* Open-label day 1 visit is within 6 months after this amendment is approved and becomes effective at the study site;
* Is willing to maintain androgen deprivation therapy with a gonadotropin-releasing hormone (GnRH) agonist/antagonist or has had a bilateral orchiectomy;

The exclusion criteria apply only to patients starting new treatment with enzalutamide after receiving placebo as randomized treatment. Each patient must not meet any of the following criteria:

* Has taken commercially available enzalutamide (Xtandi);
* Severe concurrent disease, infection, or co-morbidity that, in the judgment of the Investigator, would make the patient inappropriate for enrollment
* Known or suspected brain metastasis or active leptomeningeal disease
C: To qualify for this trial, you must have ALL of the following:

* Histologically documented adenocarcinoma of the prostate
* Cancer that has progressed while on adequate hormone therapy. This state of the disease is androgen independent prostate cancer (AIPC).
* Cancer that has spread outside the prostate (metastatic) to lymph nodes or bone. Please note that if your cancer has spread to organs (e.g., liver, lung, brain), you are not eligible for the study.
* The absence of or minimal current cancer-related pain

Please note that there are additional eligibility criteria. The study center will determine if you meet all of the criteria.

Study personnel will explain the trial in detail and answer any questions you may have if you do qualify for the study. You can then decide whether or not you wish to participate. If you do not qualify for the trial, study personnel will explain the reasons.
D: 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.)

Answer: B