Analyze the Predictive Value of Gene TMPRSS2-ETS in Response to Enzalutamide in Patients With Prostate Cancer (PREMIERE)

This is an interventional treatment trial for Hormone-refractory Prostate Cancer focused on measuring Hormone-refractory prostate cancer, Enzalutamide, TMPRSS2-ETS fusion gene Read More

Inclusion Criteria:

• Patients aged 18 years and above, willing and able to provide written informed consent.
• Prostate adenocarcinoma with histological or cytological confirmation without neuroendocrine differentiation nor small cell characteristics
• Androgen deprivation therapy with GnRH analogs or bilateral orchiectomy (pharmacological or surgical castration). Patients without bilateral orchiectomy must follow a GnRH analog therapy during the trial.
• Testosterone serum level <= 1,73 nmol/L (50 ng/dL) in screening visit.
• Patients under bisphosphonate therapy must have received stable doses for the last 4 weeks.
• Progression disease at inclusion, defined by one or more of the following three criteria during androgen deprivation therapy (according with the criterion nº 3): - PSA progression defined as two elevation of the PSA serum level with >=1 week between each measure. Patients who have received an antiandrogen must present disease progression (>=4 weeks since the last dose of flutamide or >=6 weeks since the last dose of bicalutamide or nilutamide). PSA value in screening visit must be >=2 μg/L (2 ng/mL). - Soft tissue progression defined by RECIST 1.1 criteria - Bone lesion progression defined by PCWG2 criteria, with two or more new lesions in a scintigraphy
• Metastatic disease with bone lesions detected by scintigraphy, or measurable soft tissue lesions by CT/MR. Patients with ganglionar disease will be suitable if they have at least one ganglionar lesion with smallest diameter > 2,5 cm.
• Patients without previous cytotoxic chemotherapy for prostate cancer
• Patients without previous abiraterone acetate therapy for prostate cancer - - Asymptomatic patient or mild symptomatic about prostate cancer, (answer in the question nº 3 of the Brief Pain Inventory Short From < 4) 11. ECOG = 0-1.
• Life expectancy of at least 6 months
• Patient must be able to swallow the investigation product and to follow the protocol requirements.
• Biomarker study informed consent

Exclusion Criteria:

• Active infection or other medical condition which, in the opinion of the investigator, would preclude participation in this trial.
• Known brain metastasis or leptomeningeal active involvement
• Other malignancy in the last five years, except non-melanoma skin cancer treated and resolved.
• Hematologic parameters: - Absolute neutrophil count <=1500/μL - Platelet count <100 000/μL - Haemoglobin < 5,6 mmol/L (9 g/dL)
• Liver function: Serum bilirubin, SGPT/ALT or SGOT/AST > 2,5 x ULN
• Renal function: Creatinine >177 μmol/L (2 mg/dL).
• Serum albumin <30 g/L (3,0 g/dL)
• History of epilepsy or other medical condition which could cause an epileptic crisis as syncope or transient ischemic attack in the last twelve months.
• Clinically significant cardiovascular disease.
• Known gastrointestinal (GI) disease that could interfere with the GI absorption.
• Significant surgery within 4 weeks before enrollment.
• Use of opioids to control cancer pain within 4 weeks before enrollment.
• Radiation therapy for treatment of the primary tumor in the last 3 weeks before enrollment
• Radiation therapy for treatment of metastases in the last two months
• Radionuclide therapy for treatment of bone metastasis
• Prior flutamide treatment within 4 weeks before enrollment
• Bicalutamide or nilutamide therapy within 6 weeks before enrollment
• 5-a reductase inhibitors, estrogen o cyproterone therapy within 4 weeks before enrollment
• Biologic therapy or other antitumoral drugs for the treatment of CRPC in the last 4 weeks
• History of cancer progression with ketoconazole
• Prior therapy or enrollment in a trial with an investigational product which blocks androgen synthesis (abiraterone, TAK-700, TAK-683, TAK-448) or blocks androgen receptors (ARN507, BMS 641988).
• Included in a previous trial with enzalutamide (MDV3100).
• Administration of an investigational drug in the last 4 weeks before enrollment
• Use of phytotherapy products which hormonal activity against prostate cancer or which reduce PSA levels, or systemic corticosteroids in a dose greater than the equivalent of prednisone 10mg/day, within 4 weeks before enrollment
• Hereditary fructose intolerance
• Any condition which, in the opinion of the investigator, would preclude participation in this trial.