Safety and Efficacy Trial of a RNActive®-Derived Prostate Cancer Vaccine in Hormone Refractory Disease

• Determination of the recommended dose for exploration in the phase II part [ Time Frame: 6-9 months ] [ Designated as safety issue: Yes ]
• Assessment of Safety of trial regimen [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

• Assessment of safety of the trial regimen [ Time Frame: 6-9 months ] [ Designated as safety issue: Yes ]
• evaluation of induction of immune response [ Time Frame: 2 Years ] [ Designated as safety issue: No ]
• Evaluation of the induction of immune response [ Time Frame: 2 years ] [ Designated as safety issue: No ]
• Assessment of anti-tumor activity [ Time Frame: 2 years ] [ Designated as safety issue: No ]

The purpose of this study is to determine the efficacy and safety of a new vaccine in hormone refractory prostate cancer

Immunotherapy of prostate cancer is a promising approach for the treatment of advanced or recurrent forms of prostate cancer. Recently, immunotherapy of prostate cancer has been facilitated by the identification of a number of prostate specific antigens that are expressed in healthy and tumor prostate tissues. For prostatectomized patients, such antigens offer ideal targets for immunotherapy as they are only present in tumor but not in healthy tissue. The use of prostate specific antigens in a cancer vaccine is one attractive option for cancer immunotherapy.

Inclusion Criteria:

• Signed informed consent in accordance with GCP and local regulatory requirements prior to trial participation
• Male and age ≥ 18 years (Phase I and II) and ≤ 75 years (Phase II only)
• Histologically confirmed diagnosis of adenocarcinoma of the prostate, Gleason Score available
• Patients must have been treated with hormonal therapy and may have been treated with surgery and/ or radiation therapy
• Progressive disease as defined by hormone-refractoriness and rise in PSA:

Hormone-refractoriness: Defined by a rise in PSA and/or RECIST-based progression of evaluable lesions, and/or increased number of hotspots on a bone scan, while the patient has a castrated level of testosterone. This castrated level may have been obtained by orchiectomy, or LH-RH analog ± antiandrogen. Antiandrogen must be discontinued for at least 4 weeks before study entry to exclude a withdrawal effect.

Rise in PSA: Defined by a rise in PSA levels at three consecutive time points (PSA rise over nadir, separated by > 1 week, PCWG2 criteria)

• Presence of metastatic disease is acceptable
• ECOG performance status of 0 to 1
• Life expectancy > 12 months as assessed by the investigator
• Adequate organ function :

Bone marrow function: Hemoglobin ≥ 10 g/dL; Leukocytes ≥ 3000/µL; Lymphocytes ≥ 1000/µL; Absolute neutrophil count ≥ 1500/µL; Platelet count ≥ 100000/µL Hepatic: AST and ALT ≤ 2.5 times upper limit of normal (ULN); Bilirubin ≤ 1.5 ULN Renal: Creatinine ≤ 1.5 mg/dL or creatinine clearance ≥ 60mL/min

• Concomitant LH-RH therapy continuation is acceptable
• May have had local palliative radiotherapy for bone metastasis involving less than 25% of bone marrow
• Patients requiring bisphosphonates at the time of registration into the trial are eligible (therapy initiated at least 28 days prior to first study treatment administration) and must be continued at a constant level during the study period.
• Patients of child-producing potential must agree to use contraception while enrolled in the study and for one month after the last immunization.

Exclusion Criteria:

• Other histologic type of prostate cancer (transitional cell, small cell or squamous cell cancer)
• Symptomatic brain metastasis or leptomeningeal involvement
• Patients having received or currently receiving chemo- or biological therapy for prostate cancer
• Symptomatic congestive heart failure (NYHA 3 and 4); unstable angina pectoris; significant cardiac arrhythmia
• Pulmonary disease causing dyspnea or fatigue during normal activity
• History of seizures, encephalitis or multiple sclerosis
• Inflammatory bowel disease e.g. Crohn's disease or ulcerative colitis; active diverticulitis
• Documented history of active autoimmune disorders requiring systemic immunosuppressive therapy, (e.g. sarcoidosis, lupus erythematosus, rheumatoid arthritis, glomerulonephritis or systemic vasculitis), excepting autoimmune thyroiditis with only thyroid hormone replacement and stable disease > 1 year
• Primary or secondary immune deficiency
• History of allergy requiring medication
• Active drug abuse or chronic alcoholism
• Clinically significant active infections
• Seropositive for HIV, HBV or HCV
• History of other malignancies over the last 5 years (except basal cell carcinoma of the skin)
• Uncontrolled medical condition considered as high risk for the treatment with an investigational drug including unstable diabetes mellitus, vena-cava-syndrome, known ascites and/or pleural effusion, symptomatic pleural effusion treated by puncture
• Renal insufficiency requiring dialysis
• Patients being committed to an institution by virtue of an order issued either by the judicial or the administrative authorities