A Phase II Study Evaluating the Efficacy of Enzalutamide and the Role of ARv7 in Metastatic Castration Resistant Prostate Cancer (mCRPC) Patients With Visceral Disease.

A Phase II Study Evaluating the Efficacy of Enzalutamide and the Role of ARv7 in Metastatic Castration Resistant Prostate Cancer (mCRPC) Patients With Visceral Disease.

Open label, single arm, phase II multicentre study designed to determine the clinical benefit, as measured by 3-months disease control rate (DCR) provided by enzalutamide in metastatic Castration Resistant Prostate Cancer patients with at least one visceral site involvement.

Inclusion Criteria:

1. Age > 18

2. ECOG PS 0-1-2

3. Biopsy (primary tumour or metastases) confirming the diagnosis of prostate adenocarcinoma

4. Documented measurable metastatic visceral disease (according to RECIST 1.1 criteria) considering metastases in lung or liver or extraregional lymphnodes

5. Written informed consent

6. Platelets > or = 100 x109/L; haemoglobin > or = 9 g/dl; neutrophils > or 1.5 x 109/L

7. Bilirubin < or = 2 mg/dl, AST and ALT < or = 2.5 times the UNL or < or = 5 times UNL for pts with liver metastases; serum albumin > or = the LNL

8. Patients of childbearing age should use contraceptive methods

9. Life expectancy > 3 months

10. Able to swallow the study drug and comply with study requirements;

11. Willing and able to give informed consent.

12. Ongoing androgen deprivation therapy with a GnRH analogue or orchiectomy (i.e., surgical or medical castration);

13. Patients may have received previous therapy including chemotherapy (docetaxel) last cycle must be received 3 weeks before start of experimental treatment. Hormonal treatment containing bicalutamide must be interrupted 2 weeks before start of study therapy

14. Previous radiotherapy (prostate and/or bone) is accepted but must be interrupted 3 weeks before start of experimental treatment.

15. Serum testosterone level < 1.7 nmol/L (50 ng/dL) at the Screening visit

16. Progressive disease by PSA or imaging in the setting of medical or surgical castration. Disease progression for study entry is defined as one or more of the following three criteria (according with PCWG2):

    • PSA progression defined by a minimum of three rising PSA levels with an interval of ≥ 1 week between each determination. The PSA value at the Screening visit should be ≥ 2 g/L (2 ng/ml); if the third PSA value is less than second PSA, a fourth PSA must be repeated and if it the value is higher than second must be considered as disease
    • Soft tissue/visceral disease progression defined by RECIST 1.1;
    • Bone disease progression defined by two or more new lesions on bone scan.

Exclusion Criteria:

1. Severe, concurrent disease, infection, or co-morbidity that, in the judgment of the investigator, would make the patient inappropriate for enrollment;
2. Metastases in the brain or active epidural disease;
3. History of another malignancy within the previous 5 years other than curatively treated non-melanomatous skin cancer;
4. History of seizure, including any febrile seizure, loss of consciousness, or transient ischemia attack within 12 months of enrollment (Day 1 visit), or any condition that may pre-dispose to seizure (e.g., prior stroke, head trauma with loss of consciousness requiring hospitalization);
5. Clinically significant cardiovascular disease including: Myocardial infarction within 6 months; Uncontrolled angina within 3 months; Congestive heart failure New York Heart Association (NYHA) class 3 or 4, or patients with history of congestive heart failure NYHA class 3 or 4 in the past, unless a screening echocardiogram or multi-gated acquisition scan (MUGA) performed within 3 months results in a left ventricular ejection fraction that is ≥ 45%;
6. Diagnosed or suspected congenital long QT syndrome;
7. History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes);
8. Gastrointestinal disorder affecting absorption (e.g., gastrectomy, active peptic ulcer within last 3 months);
9. Major surgery within 4 weeks prior to enrollment (Day 1 visit);
10. Prior treatment with abiraterone acetate;
11. Participation in a clinical trial about an experimental anti-androgen agent (eg. ARN-509, ODM-201, VT-464, except for placebo arm);
12. Treatment (concomitant or in the previous 2 weeks) with anti-androgens (eg. Bicalutamide, nilutamide, flutamide) or 5-a reductase inhibitors (eg. finasteride, dutasteride).