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

Brief Summary

Detailed Description

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. ADDITIONAL PARAMETERS: In order to assess any haematological or immunological effects of this novel agent or any effects on tumour response and survival, the following will be assessed: * Biochemical and Haematological Markers: including Prostate-Specific Antigen, * Immunopathological Markers: including haematological markers and indicators of cytotoxicity, * ECOG assessment, * Assessment of disease progression and survival. DATA ANALYSIS: Descriptive statistical methods will be used to summarize key data including demographics, vital sign measurements, ECG parameters, clinical laboratory parameters, immune response, tumour response, adverse events and concomitant medication. The general strategy of the safety analysis will be to examine the data summaries for any trends in safety parameters across the dose levels. No formal hypothesis will be tested. A formal data analysis will be performed after all subjects have completed the study period (28 days) and an interim analysis will be performed after the first 3 dose cohorts have been completed. For the first year, three monthly follow up reports will be produced followed by 6 monthly reports for the second year and a final follow up report when all subjects have completed 2 years of follow up. Descriptive statistical methods will be used to summarise key data including demographics, vital sign measurements, ECG parameters, clinical laboratory parameters, immune response, tumour response, adverse events and concomitant medication. The general strategy of the safety analysis will be to examine the data summaries for any trends in safety parameters across the dose levels. No formal hypothesis will be tested.

Primary Outcomes

Secondary Outcomes

• Assess haematological and immunological markers, including Prostate-Specific Antigen (PSA) and C-ReactiveProtein (CRP). Effects on tumor response and survival. Immunopathological Markers. ECOG assessment. Assessment of disease progression and survival.(Selected assessments at Day: -14 (screening); Days: 1 to 6, 11, 15, 28; Months: 3, 6, 9, 12, 24)