Multiparametric Assessment of Bone Response in mCRPC Patients Treated With Cabozantinib

Inclusion Criteria: * Histological diagnosis of prostate carcinoma, * Age \> 18 years, * Metastatic disease documented as the presence of bone lesions o bone scan associated or not to soft tissue lesions measurable at CT/RMN, * Eastern Cooperative Oncology Group (ECOG) performance status equal or less than 2 * Expected life expectancy ≥ 3 months, * Patients who have already received docetaxel, cabazitaxel and at least one next generation hormonal agent (abiraterone or enzalutamide) for metastatic disease (either hormone sensitive or castration resistant), * Subject capable to swallow the Study's medication and to comply with the Study's requirements, * Fertile patients and their partners must agree to use methods of contraception. * Signed informed consent. Exclusion Criteria: * Presence of active serious disease, active infection or co-comorbidity that may prevent the study enrollment make (at the discretion of the clinical Investigator), * Known or suspected brain metastases or active leptomeningeal dissemination, * History of other malignant neoplasm during the previous 5 years, different from the non-melanoma skin carcinoma, * Absolute Neutrophil Count (ANC) \< 1.500/µL, platelet \< 100.000/µL, or hemoglobin \< 5,6 mmol/L (\< 9 g/dL) at Screening Visit (notably: patients must not receive neither any growth factor during the previous 7 days nor any blood transfusion during the 28 days preceding the hematology sampling performed at Screening), * Total bilirubin \> 1,5 x ULN at Screening Visit, * Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 2,5 x ULN at Screening Visit, * Creatinine \> 177 µmol/L (\> 2 mg/dL) at Screening Visit, * Albumin ≤ 30 g/L (≤ 3,0 g/dL) at Screening Visit, * Alkaline Phosphatase ≥ 5 x ULN, * Prothrombin time / international normalized ratio (PT/INR) or partial thromboplastin time (PTT) test ≥ 1.3 x the laboratory ULN, * Urine protein-to-creatinine ratio (UPCR) \> 1 mg/mg (or 113.0 mg/mmol) or proteinuria \> 1 g/24 h, * History of seizures or any other seizure-predisposed pathology; history of loss of consciousness or transitory ischaemic attack during the 12 months preceding the Screening visit, * Clinically significant cardiovascular disease including: * Myocardial infarction (6 months preceding the screening), * Uncontrolled angina (3 months preceding the screening), * Congestive heart failure New York Heart Association (NYHA) class 3 or 4, congestive heart failure NYHA class 3 or 4 in the past, unless a screening echocardiogram or multi-gated acquisition scan performed within three months results in a left ventricular ejection fraction that is ≥ 45%, * History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes), * History of long QT syndrome or corrected QT interval calculated by the Fridericia formula \> 500 msec at Screening Visit, * History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place, * Hypotension as indicated by systolic blood pressure \< 86 millimeters of mercury (mmHg) at the Screening visit, * Bradycardia as indicated by a heart rate of \< 50 beats per minute on the Screening ECG, * Uncontrolled hypertension as indicated by systolic blood pressure \> 170 mmHg or diastolic blood pressure \> 105 mmHg at the Screening visit, * History of thromboembolic events, including pulmonary embolism or untreated deep venous thrombosis (6 months preceding the screening) * Gastrointestinal disorder affecting absorption (e.g., gastrectomy, active peptic ulcer disease within last 3 months), * Major surgery within 8 weeks of enrollment (Day 1 Visit). Complete healing from major surgery must have occurred 4 weeks before enrollment. Complete healing from minor surgery (e.g. simple excision, tooth extraction) must have occurred at least 7 days before enrollment. * Subjects with clinically relevant complications from prior surgery. * Concomitant therapy with anticoagulants such as warfarin or warfarin-related agents, thrombin or coagulation factor X (FXa) inhibitors, or antiplatelet agents (e.g. clopidogrel). Low molecular weight Heparin (LMWH) and low-dose aspirin for cardioprotection (per local applicable guidelines) are permitted. * Concomitant use of strong inhibitors of CYP3A4 (including, but not limiting to: ketoconazole, itraconazole, clarithromycin, indinavir, nefazodone, nelfinavir, and ritonavir). * Use of herbal products that may have hormonal anti-prostate cancer activity and/or are known to decrease PSA levels (e.g., saw palmetto) or systemic corticosteroids greater than the equivalent of 10 mg of prednisone per day within 4 weeks of enrollment (Day 1 visit). * Previously identified allergy or hypersensitivity to the study drug and/or excipients. * Bone antiresorptive drugs (e.g., zoledronic acid or denosumab) that are started within 4 weeks of enrollment (Day 1 Visit). Bone antiresorptive drugs are permitted if already ongoing before this time point. Patients will be stratified according to zoledronic acid/denosumab exposure. * Systemic treatment with radionuclides within 6 weeks before first dose of study treatment or radiotherapy on sites other than bone administrated within 4 weeks of enrollment (Day 1 Visit). Radiotherapy on bone administrated within 2 weeks of enrollment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible. Radiotherapy given with palliative intent will be permitted during study treatment. * Any condition or reason that, in the opinion of the Investigator, interferes with the ability of the patient to participate in the trial, which places the patient at undue risk, or complicates the interpretation of safety data.