A Phase I Gene Therapy Study of FP253/Fludarabine for Prostate Cancer

NCT00625430 | Unknown Phase 1 DMC

• 1 other identifier: 253/001
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Prostate Cancer

Keywords

Prostate Cancer; Gene Therapy; Fludarabine; Adenovirus; phase I

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (1)

• 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

Study Arms (1)

1

EXPERIMENTAL

Six Cohorts with escalating vector dose

Biological: Gene Directed Enzyme Prodrug Therapy, FP253/Fludarabine

Interventions

Gene Directed Enzyme Prodrug Therapy, FP253/Fludarabine BIOLOGICAL

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.

Also known as: Fludarabine

1

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects will have adenocarcinoma of the prostate which is progressive despite androgen deprivation therapy.
• 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.
• Subjects will have their prostate in situ.
• 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).
• 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.
• Be male and be 18 years of age or greater.
• Have voluntarily given written informed consent to participate in this study.
• Have an ECOG performance status of 0, 1 or 2.
• Have agreed to remain confined to the clinical testing facility for the first 3 days (2 nights) of the study.
• Have adequate baseline organ function.
• 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.

You may not qualify if:

• Subjects with any of the following criteria will NOT be eligible for participation in this study:
• Subjects who have had prior radical prostatectomy.
• Subjects who are expected to die of prostate cancer within 3 months.
• Subjects with any of the following criteria will NOT be eligible for participation in this study:
• Hypersensitivity to ciprofloxacin, fludarabine, pegfilgrastim or similar compounds.
• Contraindications to fludarabine: subjects with decompensated haemolytic anaemia.
• Contraindications to pegfilgrastim: known hypersensitivity to E. coli derived products.
• Other associated or concomitant medical conditions that would interfere with the conduct of the study in the opinion of the treating physician.
• Have used an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the first dose of study medication.
• Are immunocompromised or have used immunomodulatory agents/therapy within the 6 months preceding the initial treatment.
• Subjects who, at the sole discretion of the Investigator, are judged to be unsuitable for participation in the study.

Sponsors & Collaborators

• Biotech Equity Partners Pty Ltd: lead

Study Sites (1)

St Vincent's Hospital, Sydney

Darlinghurst, New South Wales, 2010, Australia

RECRUITING

MeSH Terms

Conditions

Prostatic Neoplasms; Adenoviridae Infections

Interventions

fludarabine

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; DNA Virus Infections; Virus Diseases; Infections

Study Officials

• David N Dalley, MB BS FRACP

  St Vincent's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Andrew M Bray, PhD

CONTACT

andrew.bray@broadvector.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: February 20, 2008
• First Posted: February 28, 2008
• Study Start: March 1, 2008
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: July 11, 2011

Record last verified: 2011-07

Locations

AU (1)