 4. Evidence of progressive disease prior to enrolment based on AT LEAST one of the following criteria: a Rising PSA: PSA progression defined by a minimum of two rising PSA levels with an interval of 1 week between each determination. The PSA value at the Screening visit should be 2 ngmL; b Non-measurable evaluable disease: 2 two or more new metastatic bone lesions by radionuclide bone scan or plain bone films x-rays; c Measurable disease RECIST 1.1 by transaxial imaging: patients must show evidence of new or progressive disease on CT or MRI scans. 