In this study, up to 21 patients with metastatic prostate cancer will receive UV1 (a therapeutic synthetic peptide vaccine) at different dose levels. The safety and tolerability of UV1 as well as immunological response will be assessed. The purpose of this study is to select a biological dose of peptides for further clinical trials.

Main treatment period is completed and reported. Follow-up ongoing.

The study is an open labeled dose-escalating phase I/IIa study of UV1 peptide vaccination in patients with androgen-sensitive metastatic prostate cancer. Patients will be prospectively enrolled in this study if diagnosis of adenocarcinoma only has been histologically confirmed and they are eligible for (or have already started up to 6 months prior to inclusion) standard GnRH-agonist first line androgen deprivation therapy (ADT) combined with anti-androgen to achieve complete androgen blockade (CAB). UV1 vaccinations will be applied simultaneously with CAB.

When indicated, patients may receive concomitant radiotherapy.

The following 2-step design will be used:

1. Conventional dose escalation with at least 3 patients per dose level (3 selected dose levels).
2. Expansion of each dose level to a total of 7 patients for assessment of immune response levels

13 UV1 vaccinations will be given during the first 6 months (week 26) of treatment, unless clinical deterioration or unacceptable toxicity is encountered. GM-CSF (Leukine ®) will be administered locally 10-15 minutes before each UV1 vaccination.

Hormone naïve patients will receive standard complete androgen blockade by GnRH-agonist (3 months depot formulation sc.) and bicalutamide 50 mg orally per day (CAB). Patients already on GnRH-agonist therapy will continue with their initial treatment with addition of bicalutamide 50 mg orally per day.

Inclusion Criteria:

• Patients with advanced oligometastatic prostate cancer (PCa) without lung and/or liver metastases who are eligible to CAB (GnRH-agonist combined with anti-androgen)

• Patients already on GnRH-agonist must have a history sPSA < 200 ng/mL prior to start of GnRH-agonist treatment. GnRH-agonist with or without bicalutamide can have been initiated up to 6 months prior inclusion.

• Must be ambulatory with an ECOG performance status of 0 or 1 and not have contraindications for MRI (pacemaker, claustrophobia, metal splints).

• Must be at least 18 years of age.

• Must have lab values as follows:

  • White Blood Cells ≥ 1.5 x 109/L
  • Platelets ≥ 100 x 109/L
  • Hemoglobin ≥ 9g/dL (≥ 5.6 mmol/L)
  • Creatinine ≤ 140 µmol/L; if creatinine is borderline, the creatinine clearance ≥ 40 mL/min;
  • Bilirubin < 20% above the upper limit of normal
  • ASAT and ALAT ≤ 1.5 the upper limit of normal
  • Albumin ≥ 2.5 g/L
  • Normal NSE
  • sPSA < 200 ng/mL.

• Signed informed consent

Exclusion Criteria:

• History of other prior malignancy, with the exception of curatively treated basal cell or squamous cell carcinoma of the skin or effectively treated malignancy that has been in remission for over 5 years and is highly likely to have been cured.

• Treatment with any other investigational medicinal product (IMP) within 4 weeks prior to first administration of study drug.

• Adverse reactions to vaccines such as anaphylaxis or other serious reactions.

• History of immunodeficiency or autoimmune disease such as rheumatoid arthritis, systemic lupus erythematosus, sclerodermia, polymyositis-dermatomyositis, juvenile onset insulin-dependent diabetes, or a vasculitic syndrome.

• Significant cardiac or other medical illness that would limit activity or survival, such as severe congestive heart failure, unstable angina, or serious cardiac arrhythmia.

• Active infection requiring antibiotic therapy.

• Known hypersensitivity to any of the components of the vaccine

• Known hypersensitivity to Leukine®, yeast derived products or any component of the product

• Patients who test positive for hepatitis B, C or HIV

• Any other anti-tumor treatment (including chemotherapy, immunotherapy, cytokines, interferons, protease inhibitors and gene therapy) administered with the exception of GnRH-agonist with or without bicalutamide started up to 6 months prior inclusion.

• Use of not permitted concomitant medication:

  • chronic corticosteroids except for asthma inhalers / topical use
  • any agent with a known effect on the immune system, unless it is being given at dose levels that are not immunesuppressive, e.g. prednisone at 10mg/day or less
  • any alternative and complementary drugs that may affect the immune system or be potentially harmful to patients participating in phase I studies.

• Any reason why, in the opinion of the investigator, the patient should not participate.