Imaging Staging and Response Prediction in Metastatic Hormono-Sensitive Prostate Cancer Patients Receiving Enzalutamide

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 (Hormono-sensitive Patients)

The aim of the study is to assess the clinical utility of 11C or 18F-Choline Positron Emission Tomography (PET)/Computed Tomography (CT) scan, Whole Body Magnetic Resonance Imaging (MRI) versus conventional bone scan and prostate-specific antigen (PSA) measurements in response prediction to treatment with Enzalutamide in Hormono-Sensitive Metastatic Prostate Cancer patients.

The study will assess 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 with Enzalutamide.

In addition measurements of serially collected circulating tumour cell (CTC) samples, cell-free tumour DNA and RNA will be performed in order to evaluate their predictive value in terms of response measurement.

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 at baseline, 2 weeks, 2 and 6, 9 and 12 months after starting androgen receptor (AR)-directed treatment. All subjects will undergo Whole Body MRI at baseline, 6, 9 and 12 months. Bone scans will be performed at baseline, 3 months, 6 and 12 months. PSA will be measured at baseline and every 4 weeks thereafter until at 12 months. CTC counts and characteristics will be measured at baseline and during Enzalutamide treatment.

Inclusion Criteria:

• Male aged 18 years or older;
• 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 11C or 18F-Choline PET/CT, 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;
• Written informed consent;

Exclusion Criteria:

• Treatment with androgen deprivation therapy with a gonadotropin-releasing hormone analogue, luteinizing hormone-releasing hormone antagonist, or bilateral orchiectomy within 6 months of enrolment (Day1 visit);
• Treatment with anti-androgens such as bicalutamide, nilutamide or flutamide within 6 weeks of enrolment (Day 1 visit);
• Treatment with 5-α reductase inhibitors (finasteride, dutasteride), estrogens, cyproterone acetate within 4 weeks of enrolment (Day 1 visit);
• 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, White blood cells < 4.0 x 10^9/L, Platelets < 100 x 10^9/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).