Prostate CancerPhase 1FP253-GDEPTNCT00625430
A Phase I Gene Therapy Study of FP253/Fludarabine for Prostate Cancer
A Phase 1 study testing Gene Directed Enzyme Prodrug Therapy, FP253/Fludarabine in people with Prostate Cancer, run by Biotech Equity Partners Pty Ltd at 1 site in Australia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostate Cancer
- What is being tested?
- Gene Directed Enzyme Prodrug Therapy, FP253/Fludarabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteAustralia
- Study dates
- Mar 2008to Dec 2012
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
- 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.
- 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).
- 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).
Show all 14Show fewer
- 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.
- Subjects MUST fulfil each of the following criteria for inclusion into this study:
- 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.
Who cannot join
- 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.
Show all 11Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
Andrew M Bray, PhD contact
Australia1 site, 1 recruiting
- Recruiting
St Vincent's Hospital, Sydney
Darlinghurst, New South Wales, 2010
About this study
Official title: A Phase I, Open-label, Dose Escalation Study to Assess the Safety and Tolerability of FP253 in Combination With Fludarabine Phosphate
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.
Read the 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.
- Conditions
- Prostate Cancer
- Being tested
- Gene Directed Enzyme Prodrug Therapy, FP253/Fludarabine
- Keywords
- Prostate Cancer, Gene Therapy, Fludarabine, Adenovirus, phase I
- Medical subject headings
- Prostatic Neoplasms, Adenoviridae Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Gene Directed Enzyme Prodrug Therapy, FP253/FludarabineBiological
Also called 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.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Six Cohorts with escalating vector dose Receives: Biological: Gene Directed Enzyme Prodrug Therapy, FP253/Fludarabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Selected assessments at Day: -14 (screening); Days: 1 to 6, 11, 15, 28; Months: 3, 6, 9, 12, 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Feb 2008 (estimated)
- Study startMar 2008
- Primary completionDec 2012 (estimated)
- Study completionDec 2012 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Biotech Equity Partners Pty Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- David N Dalley, MB BS FRACP, Principal investigator, St Vincent's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00625430
- Sponsor's protocol ID
- 253/001
- Acronym
- FP253-GDEPT
- Status last verified
- Jul 2011
- First submitted
- 20 Feb 2008
- Last updated
- 11 Jul 2011
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 11 Jul 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Open-label, Dose Escalation Study to Assess the Safety and Tolerability of FP253 in Combination With Fludarabine Phosphate
- ClinicalTrials.gov ID
- NCT00625430
- Acronym / sponsor ID
- FP253-GDEPT / 253/001
- Conditions
- Prostate Cancer
- Keywords
- Prostate Cancer, Gene Therapy, Fludarabine, Adenovirus, phase I
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- Biotech Equity Partners Pty LtdIndustry (pharma, biotech, devices)
- Study start
- Mar 2008
- Primary completion
- Dec 2012 (estimated)
- Study completion
- Dec 2012 (estimated)
- First posted
- 28 Feb 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Biological: Gene Directed Enzyme Prodrug Therapy, FP253/FludarabineSix Cohorts with escalating vector dose |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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.
- 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).
- 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).
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Gene Directed Enzyme Prodrug Therapy, FP253/FludarabineAlso: FludarabineSubjects 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. | Biological | 1 |
Primary outcome
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.
Time frame: Selected assessments at Day: -14 (screening); Days: 1 to 6, 11, 15, 28; Months: 3, 6, 9, 12, 24
1 secondary outcome
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.
Time frame: Selected assessments at Day: -14 (screening); Days: 1 to 6, 11, 15, 28; Months: 3, 6, 9, 12, 24
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jul 2011.
Related trials for Prostate Cancer
Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
Active, not recruitingObservational study
MRI Fusion Biopsy vs. Micro-Ultrasound Guided Biopsy
Prostate Cancer
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
Not yet recruitingPhase 1/2
STAR0602 With Nivolumab in Non Small Cell Lung Cancer and in Metastatic Castrate-Resistant Prostate Cancer, and STAR0602 Alone in Thymic Carcinoma
NSCLC, Non-Small Cell Lung Cancer
Recruiting
Rehabilitation and Sex Therapy to Optimize Recovery After Prostate Cancer Treatment
Prostate Cancer, Urinary Incontinence
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andrew M Bray, PhD contact
David N Dalley, MB BS FRACP principal investigator
St Vincent's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Gene Directed Enzyme Prodrug Therapy, FP253/Fludarabine in people with Prostate Cancer, run by Biotech Equity Partners Pty Ltd at 1 site in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 11 Jul 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Andrew M Bray, PhD (andrew.bray@broadvector.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. (time frame: Selected assessments at Day: -14 (screening); Days: 1 to 6, 11, 15, 28; Months: 3, 6, 9, 12, 24). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jul 2011.