Vaccine Therapy in Curative Resected Prostate Cancer Patients

Study Overview
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Brief Summary
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In this study the investigators will include patients with high risk of PSA relapse scheduled to receive curative surgical treatment. This include patients with high Gleason score (9-10) or micrometastatic disease (tumor cells detected in specimens obtained from bone marrow). They are scheduled for regular follow-ups with PSA measurements. We have previously published that some patients with metastatic prostate cancer may respond to DC-vaccination with tumor mRNA, with a decrease in PSA. PSA response is related to immunological response. Patients receiving DC-vaccination may have a reduced risk of PSA relapse or increased time to PSA relapse. Previous experience with different DC-vaccine protocols in our hospital has resulted in only minor side-effects (grade 1-2 fever, rubor, fatigue, local swelling or pain).

Official Title
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Trial of Vaccine Therapy in Curative Resected Prostate Cancer Patients Using Autologous Dendritic Cells Loaded With mRNA From Primary Prostate Cancer Tissue, hTERT and Survivin

Conditions
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Prostate Cancer

Intervention / Treatment
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* Biological: Dendritic cell vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Radical prostatectomy. 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 or pT3b Gleason score 8 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 < 0.2 µg/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. Exclusion Criteria: Previous treatment with LHRH (Luteinizing Hormone-Releasing Hormone) 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. Positive testing for syphilis (treponema pallidum), HIV, Hepatitis B and C Use of systemic glucocorticoids. Any reason why, in the opinion of the investigator, the patient should not participate.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DC-vaccine<br> | Biological: Dendritic cell vaccine<br>* Autologous Dendritic Cells Loaded With mRNA From Primary Prostate Cancer Tissue, hTERT and Survivin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to treatment failure defined by two different measurement of PSA levels >0.5 µg/L with minimum of 4 weeks interval in patients receiving treatment |  | From date of vaccination until the date of first documented treatment failure, assessed up to 8 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and toxicity of vaccination. Evaluation of immunological response. |  | Up to 8 years after vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vaccination treatment, dendritic cells