An Exploratory Phase 2, open-label, single-arm, efficacy and imaging Study of Oral Enzalutamide (XTANDI) Androgen Receptor (AR)-Directed Therapy in Hormono-Sensitive patients with Metastatic Prostate Cancer

Study purpose

Diagnostic utility of PET/CT and Whole Body MRI and early assessment of clinical response or absence thereof using state-of-the art imaging with PET/i.v. contrast enhanced CT in (chemotherapy-sensitive) metastatic hormone-sensitive prostate cancer patients undergoing treatment with Enzalutamide.


The detection of tumour deposits/metastatic sites in metastatic prostate cancer is notoriously difficult and the conventionally used PSA (reflecting tumour mass and differentiation grade of prostate cancer cells scored as Gleason score in primary tumours) and bone scintigraphy do not provide accurate information with regard to responses to treatment. There is an unmet need for robust and reproducible imaging technology allowing accurate quantification and qualification of bone plus soft tissue metastases and which are useful to early predict responses and early detect progressive disease cq. heterogeneity in tumour responses to novel agents.

Drug development and clinical practice are hampered by the poor methods and criteria to assess progression with the risk of prematurely discontinuing effective therapy in patients with metastatic prostate cancer because of apparent initial progression on bone scan. Ineffective treatment may be stopped earlier if we have methodology to accurately predict favourable or lack of favourable responses, whereas early prediction of favourable responses will allow better patient selection and true patient-tailored treatment. This will be an asset for drug development programmes and result in decreased costs.

Aim of the study

  • To evaluate the feasibility of PET/CT, or WB MRI or both to determine metastatic tumour load before and after treatment with Enzalutamide in Hormono-Naïve metastatic Prostate Cancer 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 metastatic PCa patients.


Metastatic hormone-sensitive prostate cancer patients with progressive metastatic disease requiring treatment and who have at least one measurable metastasis on either PET/CT or WB MRI or both.

Inclusion Criteria

  • Histologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features.
  • Three consecutive rises of PSA, 1 week apart, resulting in two 50% increases over the nadir, with PSA of at least > 2 ng/mL but preferably >20 ng/mL.
  • Progressive disease defined by rising PSA levels plus by evidence of progressive and measurable soft tissue or bone disease by PET/CT (11C or 18F choline PETCT, separate or one-stop shop with i.v. contrast CT thorax and abdomen), Whole Body MRI or both.
  • No prior treatment with cytotoxic chemotherapy
  • Eastern Cooperative Oncology Group (ECOG) score 0-2
  • A life expectancy of at least 12 months.

Exclusion Criteria

  • Treatment with androgen deprivation therapy with a GnRH analogue, LHRH antagonist, or bilateral orchiectomy within 6 months of enrolment.
  • Treatment with anti-androgens such as bicalutamide, nilutamide or flutamide within 6 months of enrolment.
  • Treatment with 5-αreductase inhibitors (finasteride, dutasteride) estrogens, cyproterone acetate within 4 weeks of enrolment.
  • 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 Choline (11C or 18F)-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