E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prostatic cancer patients who have received curative surgery. |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Safety and toxicity of vaccination with DCs transfected with h-TERT mRNA, survivin mRNA and autologous tumor cell mRNA andlymphnodepletion treatment in patients with prostatic cancer. Time to treatment failure defined by two different measurement of PSA levels >0.5 with minimum of 4 weeks interval. At this time the patients will be referred to standard radiation therapy. |
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E.2.2 | Secondary objectives of the trial |
Evaluation of immunological responses, time to disease progression and survival time. Safety and toxicity of vaccination with DCs transfected with mRNA for hTERT and survivin and autologous tumor mRNA from patients following curative surgery. Determine immunological response to the vaccine (induction of specific T-cell response) and time of disease progession and survival time. Monitor minimal residual disease in bone marrow and blood and compare results with immunological responses.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Radical prostatectomy with negative resection margins. Preferably accessible tumor tissue with enough volume and quality for vaccine production (extraction of tumor mRNA). • Pathological stage pT2 - pT3b and Gleason score 7B-10, pN0, pN+ or pNx. • Must be ambulatory with an ECOG performance status 0 or 1. • Tumor cells detected in bone-marrow samples (micrometastatic disease). Patients with Gleason score 9-10 may also be included with negative bone-marrow aspiration. Bone-marrow aspirates and plasma for microRNA will be obtained before start of surgery. • Must be at least 18 years of age and less than 75 years. • PSA < 0.2µg/L within 6 weeks after surgery. • Must have lab values as the following: ANC ≥ 1.5 x 109/L Platelets ≥ 100 x 109/L Hb ≥ 9 g/dL (≥ 5.6 mmol/L) Creatinine ≤ 140 μmol/L (1.6 mg/dL); if borderline, the creatinine clearance ≥ 40 mL/min Bilirubin within the upper limit of normal ASAT and ALAT ≤ 2.5 the upper limit of normal Albumin levels above lower normal value • No metastasis on bone scans or MRI, last 3 months before inclusion. • Signed informed consent and expected cooperation of the patients for the treatment and follow up must be obtained and documented according to ICH/GCP, and national/local regulations
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E.4 | Principal exclusion criteria |
• Previous treatment with LHRH agonist. • Previous anti-androgen treatment (Casodex). • History of prior malignancy within the last 5 years, with the exception of curatively treated basal cell carcinoma. • Active infection requiring antibiotic therapy. • Significant cardiac or other medical illness that would limit activity or survival, such as severe congestive heart failure, unstable angina, or serious cardiac arrhythmia. • Adverse reactions to vaccines such as asthma, anaphylaxis or other serious reactions. • History of immunodeficiency or autoimmune disease such as rheumatoid arthritis, systemic lupus erythematosus, scleroderma, polymyositis-dermatomyositis, juvenile onset insulin dependent diabetes, or a vasculitic syndrome. • Use of systemic glucocorticoids. • Negative testing for HIV, Hepatitis B and C • Any reason why, in the opinion of the investigator, the patient should not participate.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary end-point of this study is: Time to PSA levels >0.5 with minimum 4 weeks interval.
The secondary end-points of this study are: Safety and toxicity of the vaccination with mRNA transfected DCs, especially grade 3/4 adverse events assessed by reference to the NCI Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE). Biochemistry, hematology, vital signs and ECOG performance status will also be assessed. Evaluation of immunological responses in terms of SI ≥ 2 or delta Δ ≥ 10.000 measured by the 3H-thymidine proliferation test |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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End of trial when 30 patients have undergone the treatment and follow up period. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 11 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 11 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |