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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00625430




Registration number
NCT00625430
Ethics application status
Date submitted
20/02/2008
Date registered
28/02/2008
Date last updated
11/07/2011

Titles & IDs
Public title
A Phase I Gene Therapy Study of FP253/Fludarabine for Prostate Cancer
Scientific title
A Phase I, Open-label, Dose Escalation Study to Assess the Safety and Tolerability of FP253 in Combination With Fludarabine Phosphate
Secondary ID [1] 0 0
253/001
Universal Trial Number (UTN)
Trial acronym
FP253-GDEPT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prostate Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Gene Directed Enzyme Prodrug Therapy, FP253/Fludarabine

Experimental: 1 - Six Cohorts with escalating vector dose


Other interventions: Gene Directed Enzyme Prodrug Therapy, FP253/Fludarabine
Subjects within a treatment group will be administered a single transrectal intraprostatic injection of FP253.
Group A: 1 x 10Exp9 virus particles (VP); Group B: 3.2 x 10Exp9 VP; Group C: 1 x 10Exp10 VP; Group D: 3.2 x 10Exp10 VP; Group E: 1 x 10Exp11 VP; Group F: 3.2 x 10Exp 11 VP.
If there are no dose-limiting toxicities, three additional patients may be treated at the highest dose.
Twenty four hours following administration of the FP253, subjects will receive a first dose of fludarabine phosphate (20mg/m2 administered as an intravenous bolus). The first dose of fludarabine phosphate will be followed by 4 further doses at 24 hour intervals on treatment Days 3 to 6.

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
Selected assessments at Day: -14 (screening); Days: 1 to 6, 11, 15, 28; Months: 3, 6, 9, 12, 24
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
Selected assessments at Day: -14 (screening); Days: 1 to 6, 11, 15, 28; Months: 3, 6, 9, 12, 24

Eligibility
Key inclusion criteria
Inclusion Criteria (Prostate Cancer Categorization):

Subjects will have adenocarcinoma of the prostate which is progressive despite androgen
deprivation therapy.

Subjects MUST fulfil each of the following criteria for inclusion in this study:

1. Biopsy of the tumour must have been performed and histological status of
adenocarcinoma of the prostate documented. The diagnostic prostatic biopsy will have
taken place at least 4 weeks prior to the planned day 1.

2. Subjects will have their prostate in situ.

3. Biochemical evidence of prostate cancer recurrence; defined as a rise over 3
successive PSA measurements spanning a minimum of 3 months (no lower limit of PSA
exclusion).

4. Subjects will have been treated with androgen deprivation therapy and will remain on
hormone therapy for the duration of the study (LHRH agonists with or without
antiandrogens, or bilateral orchidectomy).

5. The Investigator should be able to localise the tumour either by digital rectal
examination (DRE) (i.e. tumour palpable); or the tumour should be visible on
transrectal ultrasound (TRUS). Localization of tumour will be documented and should be
adequate to allow the Investigators to inject it. Repeated TRUS will be at the
discretion of the Investigator General.

Inclusion Criteria (General):

Subjects MUST fulfil each of the following criteria for inclusion into this study:

1. Be male and be 18 years of age or greater.

2. Have voluntarily given written informed consent to participate in this study.

3. Have an ECOG performance status of 0, 1 or 2.

4. Have agreed to remain confined to the clinical testing facility for the first 3 days
(2 nights) of the study.

5. Have adequate baseline organ function.

6. Have an ECG which is normal, or, if there is any abnormality, it must be considered to
be clinically insignificant in the context of the trial.
Minimum age
18 Years
Maximum age
No limit
Gender
Males
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria (Prostate Cancer Categorization):

Subjects with any of the following criteria will NOT be eligible for participation in this
study:

1. Subjects who have had prior radical prostatectomy.

2. Subjects who are expected to die of prostate cancer within 3 months.

Exclusion Criteria (General):

Subjects with any of the following criteria will NOT be eligible for participation in this
study:

1. Hypersensitivity to ciprofloxacin, fludarabine, pegfilgrastim or similar compounds.

2. Contraindications to fludarabine: subjects with decompensated haemolytic anaemia.

3. Contraindications to pegfilgrastim: known hypersensitivity to E. coli derived
products.

4. Other associated or concomitant medical conditions that would interfere with the
conduct of the study in the opinion of the treating physician.

5. Have used an investigational drug within 30 days or 5 half-lives (whichever is longer)
preceding the first dose of study medication.

6. Are immunocompromised or have used immunomodulatory agents/therapy within the 6 months
preceding the initial treatment.

7. Subjects who, at the sole discretion of the Investigator, are judged to be unsuitable
for participation in the study.

Study design
Purpose of the study
Treatment
Allocation to intervention
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Unknown status
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
St Vincent's Hospital, Sydney - Darlinghurst
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Biotech Equity Partners Pty Ltd
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The primary objective of this study is to determine the safety and tolerability of a
gene-directed enzyme prodrug therapy 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. PNP converts systemically administered
fludarabine (the prodrug) into 2-fluoroadenine (the active agent) at the site where FP253 has
been administered (the prostate). This localized conversion is expected to provide
organ-targeted chemotherapy that should reduce the systemic side effects associated with
classical chemotherapy and also reduce the risk of debilitating damage to tissues surrounding
the prostate.
Trial website
https://clinicaltrials.gov/show/NCT00625430
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
David N Dalley, MB BS FRACP
Address 0 0
St. Vincent's Hospital-Manhattan
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Andrew M Bray, PhD
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
andrew.bray@broadvector.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT00625430