A Phase I, Open-label, Dose Escalation Study to Assess the Safety and Tolerability of FP253 in Combination With Fludarabine Phosphate

OBJECTIVES: The primary objective of this study is to determine the safety and tolerability of FP253 for prostate cancer. FP253 contains an ovine atadenovirus that expresses the E. coli enzyme purine nucleoside phosphorylase (PNP) under the control of a prostate-directed promoter.

SUBJECT POPULATION: Up to eighteen male subjects (6 groups of 3 subjects) who have a histological diagnosis of adenocarcinoma of the prostate, still have their prostate in situ, have evidence of progressive disease despite continuous androgen deprivation therapy and who meet all eligibility criteria, will be enrolled into this study.

STUDY DESIGN: This study is designed as an open-label, dose escalation trial in which each patient in a cohort will receive a single defined dose. Subjects will be enrolled consecutively into 6 escalating dose groups each of 3 subjects. Each subject will receive the treatment as outlined in the protocol and will be followed up for a further 2 years at regular intervals for life, as defined by current standard of care.

TREATMENT: Subjects will be administered a single injection of FP253 followed by five doses of Fludarabine phosphate as outlined in the Intervention section.

SAFETY PARAMETERS: Adverse events will be recorded and physical examinations, 12-lead ECG, vital sign monitoring, urinalysis and collection of blood samples for pathology laboratory tests will be performed at regular intervals during the study to monitor safety. The shedding of viral vector will be monitored as per regulatory requirement until negative.