Docetaxel or Hormone Therapy as Second Line Treatment in Patients With Asymptomatic or Oligosymptomatic Metastatic Castration-resistent Prostate Cancer (mCRPC) Progressing After Abiraterone or Enzalutamide.

A Randomized Multicenter Phase III Trial Comparing Docetaxel or Hormone Therapy as Second Line Treatment in Patients With Asymptomatic or Oligosymptomatic Metastatic Castration-resistent Prostate Cancer (mCRPC) Progressing After Abiraterone or Enzalutamide.

This is a randomized phase 3 trial aiming to compare the efficacy of docetaxel and hormone therapy as second line treatment in patients with mCRPC progressing after therapy with abiraterone or enzalutamide.

Patients will be randomized 1:1 to receive docetaxel or hormone therapy (abiraterone or enzalutamide based on previous treatment).

Docetaxel (standard) will be administered for 10 cycles (maximum).

Hormone therapy (experimental) will be administered until progression or unacceptable toxicity.

Inclusion Criteria:

• Histologically or cytologically confirmed adenocarcinoma of the prostate
• Distant metastatic disease
• Previous first line treatment with abiraterone or enzalutamide for 6 cycles interrupted at least 2 weeks before randomization
• Patients must be ≥ 18 years of age
• Patients must have castrate serum level of testosterone of < 0.5 ng/mL ( 1.7 nmol/L)
• Asymptomatic or Oligosymptomatic disease
• Progressive disease according to Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria
• ECOG performance status (PS) of 0-2
• Sexually active males must use an accepted and effective method birth control measure
• Written informed consent

Exclusion Criteria:

• Prior exposure to docetaxel or abiraterone for treatment of hormone-sensitive metastatic prostate cancer (mHSPC)

• History of adrenal insufficiency or hypoaldosteronism

• Any medical condition that would make prednisone use contraindicated

• Any medical condition that would make docetaxel use contraindicated

• Patients unable to swallow orally administered medication

• Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV) requiring antiretroviral therapy

• Other malignancy within the last 5 years, except for adequately treated non melanoma skin cancer, bladder cancer (pTis, pTa, pT1) or other solid tumours curatively treated with no evidence of disease for > 5 years

• Participation in another clinical study with an investigational product within 30 days prior to randomization

• Persistent toxicities [>Common Terminology Criteria for Adverse Event (CTCAE) grade 1)] caused by previous cancer therapy prior to randomization

• Uncontrolled medical conditions including diabetes mellitus. Clinically significant cardiovascular disease (e.g.: uncontrolled hypertension or arrhythmia, unstable angina pectoris, congestive heart failure (CHF), vascular disease (arterial thrombosis) and myocardial infarction within < 6 months

• Left ventricular ejection fraction < 50%

• Peripheral neuropathy [> CTCAE grade 2]

• Inadequate bone marrow function defined as:

  • haemoglobin < 9.0 g/dL
  • absolute neutrophils count (ANC) <1.5 x 109/L (> 1500 per mm3)
  • platelet count <100 x 109/L (>100,000 per mm3)

• Inadequate renal and hepatic function, defined as:

  • total serum bilirubin > 1,0 x ULN
  • AST/SGOT o ALT/SGPT > 1,5 x ULN
  • calculated creatinine clearance < 40 mL/min
  • potassium level < 3,5 mmol/L
  • Child-Pugh class C