In this Phase I study, patients with hormone-sensitive Prostate Cancer (PC) and lymph node metastases are treated with the cancer vaccine Bcl-xl_42-CAF09b. The aim of the study is to clarify the safety and toxicity of the vaccine and also the immunological effect.

The vaccine Bcl-xl_42-CAF09b is composed of the peptide Bcl-xl_42 and the adjuvant CAF09b. The B-cell lymphoma extra large protein (Bcl-xl) protein plays a vital role in the cancer cell's ability to avoid programmed cell death (apoptosis) and is upregulated in a variety of cancerous diseases. Bcl-xl_42 is a peptide fragment of the full protein and preclinical studies have shown that vaccination with this peptide (Bcl-xl) can activate the immune system and thereby lead to the death of cancer cells. In order to improve the activation of the immune system, adjuvant CAF09b is added; Preclinical studies have shown that special intraperitoneal (IP) injections of CAF09b improve the activation of the immune system.

Background:

In this Phase I study, patients with hormone-sensitive Prostate Cancer (PC) and lymph node metastases are treated with the cancer vaccine Bcl-xl_42-CAF09b. The aim of the study is to clarify the safety and toxicity of the vaccine and also the immunological effect.

Patients included should be on Bicalutamid treatment upon inclusion. The vaccine Bcl-xl_42-CAF09b is composed of the peptide Bcl-xl_42 and the adjuvant CAF09b. The B-cell lymphoma extra large protein (Bcl-xl) protein plays a vital role in the cancer cell's ability to avoid programmed cell death (apoptosis) and is upregulated in a variety of cancerous diseases. Bcl-xl_42 is a peptide fragment of the full protein and preclinical studies have shown that vaccination with this peptide (Bcl-xl) can activate the immune system and thereby lead to the death of cancer cells.

In order to improve the activation of the immune system, adjuvant CAF09b is added; Preclinical studies have shown that special intraperitoneal (IP) injections of CAF09b improve the activation of the immune system.

The CAF09 adjuvant has been developed by Statens Serum Institut (SSI). It is a three-component adjuvant system, composed of cationic liposomes (DDA-MMG1) with complex bound synthetic double-stranded RNA (Poly(I:C)2). The adjuvant was developed as a means to induce cytotoxic CD8+ T-cell responses against vaccine antigens and intended for use in vaccines against disease targets such as cancers, human immunodeficiency virus or Hepatitis C virus. The Poly(I:C) component has previously been in clinical studies as a cancer treatment. Poly(I:C) is known for its pyrogenic activity but upon formulation in the cationic liposome system, CAF09, the pyrogenic effect is significantly reduced.

Methods:

20 patients will be included in this phase I trial. 10 patients will be included in arm A and 10 patients in arm B. Arm a will recieve 3 vaccines every second week IM and thereafter 3 vaccines every second week IP. Arm B will first receive 3 vaccines every second week IP and thereafter every second week IM. All 20 patients will recieve 6 vaccines all in all. This is not randomized - the first 10 patients included will be in arm A and the last 10 patients included will be in arm B.

Patients will be followed with clinical controls every second week.

Inclusion Criteria:

1. Age ≥ 18 years

2. Histologically Verified Adenocarcinoma Prostatae

3. Diagnostic and / or histologically verified lymph node metastases

4. ECOG Performance Status ≤2

5. Primary anti-androgen treatment started

6. Adequate haematological, renal and hepatic function:

   1. Neutrophil granulocytes ≥ 1.5 x 109 / l
   2. Platelet counts ≥ 100 x 109 / l
   3. hemoglobin ≥ 5.6 mmol / l
   4. Serum creatinine ≤ 1.5 times upper normal limit
   5. AST or ALAT ≤ 2.5 times upper normal limit
   6. serum bilirubin ≤ 1.5 times upper normal limit
   7. Alkaline phosphatase ≤ 2.5 times upper normal limit
   8. INR <1.5 / PP <40

Exclusion Criteria:

1. Verified bone or visceral metastases
2. Serious allergy or previous anaphylactic reactions
3. Known hypersensitivity to any of the active substances or to any of the excipients.
4. Other malignant disease within the last three years, rendering planocellular and basocellular skin carcinoma
5. Known infection with HIV, hepatitis B and C virus, regardless of whether the infection is kept calm with medical treatment
6. Severe medical disorder, severe asthma, severe COPD, poorly regulated cardiovascular disease or diabetes
7. Active autoimmune disease, e.g. autoimmune neutropenia / thrombocytopenia or hemolytic anemia, systemic lupus erythematosus, scleroderma, myasthenia gravis, goodpasture syndrome, Addison's disease, Hashimoto's thyroiditis, active grave disease, morbus chrohn or ulcerative colitis
8. Major gastrointestinal surgical procedures within the last 3 months
9. Previous treatment with other cancer vaccine
10. Concomitant immunosuppressive treatment including prednisolone and methotrexate
11. Ongoing anticoagulant treatment (treatment with acetylsalicylic acid and clopidogrel is allowed)
12. Psychiatric disease which, according to the investigator's discretion, may affect compliance
13. Co-administration with other experimental drugs.

Not a randomized study. The first 10 patients included will be treated in arm A - the last 10 will be treated in arm B.