An Exploratory Phase 2, open-label, single-arm, efficacy and imaging Study of Oral Enzalutamide (XTANDI) Androgen Receptor (AR)-Directed Therapy in Chemo-Naïve patients with Progressive Prostate Cancer who have failed Androgen Deprivation Therapy (CRPC patients) (NCT02814968)

Aim of the study

  • To evaluate the feasibility of 18F-FDG PET/CT, or WB MRI or both to determine metastatic tumour load before and after treatment with Enzalutamide in CRPC patients.
  • To evaluate how these 2 imaging modalities perform compared to traditional serial PSA measurements and bone scan in assessing metastatic tumour load, progressive disease and response to treatment in CRPC patients.

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
  • Three consecutive rises of PSA, 1 week apart, resulting in two 50% increases over the nadir, with PSA of at least > 5 ng/mL, but preferably >10 ng/mL.
  • Progressive disease despite androgen deprivation therapy as defined by rising PSA levels plus by evidence of progressive and measurable soft tissue or bone disease by PET/CT (18F-FDG, separate or one stop shop), Whole Body MRI or both.
  • Castrate serum levels of testosterone < 50 ng/dL or < 1.7 nmol/L.
  • Anti-androgen withdrawal for at least 6 weeks for bicalutamide, nilutamide or flutamide for at least 6 weeks.
  • No prior treatment with cytotoxic chemotherapy
  • Eastern Cooperative Oncology Group (ECOG) score 0-2
  • A life expectancy of at least 12 months

Exclusion Criteria

  • Severe concurrent disease, infection, or co-morbidity that, in the judgment of the Investigator, would make the patient inappropriate for enrolment;
  • 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;
  • Total bilirubin, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) 2.5 times the upper limit of normal at the Screening visit;
  • Creatinine > 177 µmol/L (2 mg/dL) at the Screening visit;
  • Hemoglobin <6 mmol/L, WBC < 4.0 x 109/L, platelets < 100 x 109/L.
  • History of seizure or any condition that may predispose to seizure. Also, history of loss of consciousness or transient ischemic attack within 12 months of enrolment (Day 1 visit);
  • Contra-indication for MRI (e.g. pacemaker).

Study design (e.g. open-label):

Metastatic prostate cancer patients eligible for 1st line hormonal treatment will undergo treatment with Enzalutamide (XTANDI). Subjects will receive 1dd 160 mg Enzalutamide orally continuously until progressive disease occurs. All subjects will undergo 18F-FDG PET/CT scans and WB MRI at specific time points. PSA will be measured at baseline and every 4 weeks thereafter until at 12 months. Circulating tumour cells (CTC) counts and characteristics will be measured at baseline, and various time points thereafter.

Sample size


Primary Endpoints

  • Progression-Free Survival (PFS) at 6 and 12 months
  • Conversion of the PET signal

Secondary Endpoints

  • Biochemical (PSA) response defined as prostate-specific antigen (PSA) nadir.
  • Time to PSA Progression
  • Symptomatic Skeletal Event (SSE)
  • CTC measurements and comparison to radiological PFS at 6 and 12 months
  • Circulating hormones
  • Biomarkers of bone turnover
  • Quality of life