|- candidate number||15290|
|- NTR Number||NTR4124|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd.|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||19-aug-2013|
|- Secondary IDs||NL39923.000.12 METC 2013-146; TRC number: A301028|
|- Public Title||Oncolytic adenovirus therapy as an adjuvant treatment for localised prostate cancer.|
|- Scientific Title||Oncolytic adenovirus therapy as an adjuvant treatment for localised prostate cancer.|
|- ACRONYM||Oncolytic adenovirus therapy in PCa|
|- hypothesis||Ad[I/PPT-E1A] is a safe and well tolerated adjuvant treatment for localised prostate cancer before radical prostatectomy.|
|- Healt Condition(s) or Problem(s) studied||Localized prostate cancer, Adjuvant treatment, Radical prostatectomy, Oncolytic adenovirus therapy|
|- Inclusion criteria||1. Men 35-70 years old 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 (based on Erasmus MC reference values):
- Neutrophils >= 1.4 x 10E9 /L
- Lymphocyte counts >= 0.5 x 10E9/L
- Platelets >= 150 x 10E9 /L
- Haemoglobin >= 8.6 mmol/L
7. Chemistry (based on Erasmus MC reference values):
- Aspartate aminotransferase (AST) < 37 U/L
- Alanine aminotransferase (ALT) < 41 U/L
- Creatinin < 115 ¦̀mol/L
- Total bilirubin < 17 ¦̀mol/L
8. Detectable titre of anti-Adenovirus antibodies
9. Living within one hour travel distance of the hospital
|- Exclusion criteria||1. Patients with >= 20% risk on lymph node involvement according to the Memorial Sloan-Kettering Cancer Centre (MSKCC) Prostate Cancer Prediction Tool for pre-treatment risk assessment. This tool is available at http://www.mskcc.org/mskcc/html/10088.cfm|
2. Prior androgen ablation hormonal therapy (except treatment with finasteride - if discontinued > 3 months prior to inclusion in current protocol)
3. Prior prostatic surgical procedure during which tissue was resected, except biopsies.
4. Patients on systemic, inhaled, or topical corticosteroids
5. Concurrent treatment with immunosuppressive drugs (Imuran, cyclophosphamide, etc.)
6. Patients with uncontrolled infections, including uncontrolled infections of the urinary tract (defined as viral, bacterial or fungal infections requiring specific therapy)
7. Patients known to be HIV-positive or having another severe immunodeficiency
8. Prostatitis during the past 12 months
|- mec approval received||yes|
|- multicenter trial||no|
|- Type||2 or more arms, non-randomized|
|- planned startdate ||1-sep-2013|
|- planned closingdate||1-sep-2016|
|- Target number of participants||18|
|- Interventions||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.|
|- 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.|
|- Timepoints||Day 0 (= day of injection), 1, 2, 4, 7, 14, 21, 22 (= day of radical prostatectomy) after injection and week 2 + 6 and month 3, 6, 9, and 12 after radical prostatectomy.|
|- Trial web site||N/A|
|- CONTACT FOR PUBLIC QUERIES||Prof. Dr. C.H. Bangma|
|- CONTACT for SCIENTIFIC QUERIES||Prof. Dr. C.H. Bangma|
|- Sponsor/Initiator ||Erasmus Medical Center|
(Source(s) of Monetary or Material Support)
|ZON-MW, The Netherlands Organization for Health Research and Development, European Union|
|- Brief summary||Background of the study:|
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.
Objective of the study:
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.
Exploratory Phase I dose-escalating study to assess the safety and tolerability of Ad[I/PPT-E1A].
12 - 18 men aged 35-70 years with localised prostate cancer scheduled for radical prostatectomy.
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.
Primary study parameters/outcome of the study:
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.
Secundary study parameters/outcome of the study:
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.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness:
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.
|- Main changes (audit trail)|
|- RECORD||19-aug-2013 - 4-sep-2013|