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
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
- Biochemical and Haematological Markers: including Prostate-Specific Antigen,
- Immunopathological Markers: including haematological markers and indicators of
- 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.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Adverse events will be recorded. Physical examinations, 12-lead ECG, vital sign monitoring, urinalysis and collection of blood samples for pathology testing will be performed. Viral DNA and infectious virus will be monitored in serum and urine samples.
Selected assessments at Day: -14 (screening); Days: 1 to 6, 11, 15, 28; Months: 3, 6, 9, 12, 24
David N Dalley, MB BS FRACP
St. Vincent’s Hospital.
Australia: Department of Health and Ageing Therapeutic Goods Administration