The main objective is to evaluate the safety and tolerability of Ad[I/PPT-E1A] as an adjuvant treatment for localised prostate cancer before radical prostatectomy. A secondary objective is to explore the histopathological and immunological effects…
ID
Source
Brief title
Condition
- Reproductive neoplasms male malignant and unspecified
- Prostatic disorders (excl infections and inflammations)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study parameter is dose-limiting toxicity between 1x10E11 and 5x10E12
Virus Particles Ad[I/PPT-E1A], defined as any irreversible grade 3 or 4
toxicity.
Secondary outcome
Secondary study parameters are histopathological changes with respect to
necrosis and inflammatory features, immunological changes with respect to the
systemic and local innate and adaptive immune system profile, and the presence
of tumour-specific and adenovirus-specific T
cells in blood and the prostate before, during and after Ad[I/PPT-E1A]
oncolytic adenovirus therapy.
Background summary
Curative therapies for prostate cancer, like radical prostatectomy, often fail
due to the recurrence of the disease that can be treated by palliative
treatment only. The efficacy of surgery may be increased by adjuvant therapy
aimed at the reduction of the amount of malignant tissue prior to surgery.
Oncolytic adenoviruses that selectively kill cells of interest have shown
promising results in patients with prostate cancer who failed radiotherapy and
as an adjuvant to radiotherapy for localized disease. Even long term effects
were observed, which most likely can be
explained by the induction of anti-tumour immunity.
Study objective
The main objective is to evaluate the safety and tolerability of Ad[I/PPT-E1A]
as an adjuvant treatment for localised prostate cancer before radical
prostatectomy. A secondary objective is to explore the histopathological and
immunological effects induced by Ad[I/PPT-E1A] to get more insight in the
mechanism of action of oncolytic adenovirus therapy.
Study design
Exploratory Phase I dose-escalating study to assess the safety and tolerability
of Ad[I/PPT-E1A].
Intervention
Ad[I/PPT-E1A] will be administered 3 weeks prior to radical prostatectomy at
1x10E11, 1x10E12 or 5x10E12 Virus Particles by intraprostatic injection under
guidance of transrectal ultrasound in 4 equal deposits with a total volume of 1
ml.
Study burden and risks
The burden associated with participation in this trial involves a single
intraprostatic virus injection in 4 deposits 3 weeks prior to the radical
prostatectomy and blood and urine collection at regular intervals from 4 weeks
prior to surgery till 12 months after surgery. The risks for the patient
associated with local administration of an oncolytic adenovirus at the proposed
dosages are considered negligible. There are no clinical data for Ad[I/PPT-E1A]
available yet and therefore a potential benefit for the patients may not be
expected.
Wytemaweg 80
Rotterdam 3015 CN
NL
Wytemaweg 80
Rotterdam 3015 CN
NL
Listed location countries
Age
Inclusion criteria
1. Men * 18 years, scheduled to undergo radical prostatectomy in Erasmus MC
2. Histologically proven adenocarcinoma of the prostate
3. Clinical Stage T1b-T2, Nx-N0, M0 disease
4. Life expectancy > 10 years according to the European Association of Urology guidelines 2009
5. Written informed consent
6. Haematology:
- Absolute neutrophil count ANC * 1.5 x 10E9 /L
- Lymphocyte counts * 0.8 x 10E9/L
- Platelets * 100 x 10E9 /L
- Haemoglobin * 6.2 mmol/L
7. Chemistry:
- Aspartate aminotransferase (AST) * 2.5 x ULN
- Alanine aminotransferase (ALT) * 2.5 x ULN
- Creatinin * 1.5 x ULN
- Total bilirubin * 1.5 x ULN
8. Living within one hour travel distance of the hospital
9. Green light from anaesthesist, fit to undergo RP
Exclusion criteria
1. Prior androgen ablation hormonal therapy (except treatment with finasteride - if discontinued >
3 months prior to inclusion in current protocol)
2. Prior prostatic surgical procedure during which tissue was resected, except biopsies.
3. Continuous daily use of oral prednisone, oral dexamethasone, or other systemic corticosteroids for more than 14 days within 3 months prior to screening (inhaled, nasal and local steroids are allowed (e.g. joint injection)
4. Concurrent treatment with immunosuppressive drugs (Imuran, cyclophosphamide, etc.).
5. Patients with uncontrolled infections, including uncontrolled infections of the urinary tract
(defined as viral, bacterial or fungal infections requiring specific therapy)
6. Patients known to be HIV-positive or having another severe immunodeficiency
7. Prostatitis during the past 12 months
8. Any condition which, in the opinion of the investigator, would prevent full and safe participation in this trial, or would interfere with the evaluation of the trial endpoints
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2012-000853-30-NL |
| CCMO | NL39923.000.12 |
| OMON | NL-OMON24928 |