To determine whether PROSTVAC alone or in combination with GM-CSF is effective in prolonging overall survival in men with few or no symptoms from metastatic, castrate-resistant prostate cancer.

Phase 1

Conditions: Asymptomatic or Minimally Symptomatic Metastatic, Castrate-Resistant Prostate Cancer
MedDRA version: 18.1Level: PTClassification code 10060862Term: Prostate cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2010-021196-85-IS

Lead Sponsor: Bavarian Nordic, Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Male

Target Recruitment: 1200

Inclusion Criteria

1. Signed Informed Consent
2.Men, =18 years of age with documented asymptomatic or minimally
symptomatic metastatic castration-resistant prostate cancer.
3. Castrate testosterone level < 50 ng/dl
4. Documented progressive disease post-surgical castration or during
androgen suppression therapy or during complete androgen blockade
therapy and withdrawal. Documented by either criterion a (Radiological
progression), OR criterion b (PSA progression).
a. Radiological progression defined as any new/enlarging bone
mestatases or new/enlarging lymph node disease, consistent with
prostate cancer.
OR
b. PSA progression defined by sequence of rising values separated by >
1 week (2 separate increasing values) over a threshold minimum of 2.0
ng/ml. (PCWG2 PSA eligibility criteria).
5. Chemotherapy naïve. No prior chemotherapy for metastatic prostate
cancer. Neo-adjuvant or adjuvant chemotherapy for primary prostate
cancer is permissible if >3 years prior.
6. Vaccinia-experienced (previous smallpox vaccination).
7. ECOG Performance Score of 0 or 1.
8. Life expectancy = 1 year.
9. Bone Marrow function:
- Absolute neutrophil count = 1,500/mm3
- Hemoglobin = 10 g/dL
- Platelet count = 100,000/mm3
10. Hepatic Function:
- AST and ALT = 2.5 times upper limit of normal (ULN)
- Bilirubin = 1.5 times ULN
11. Renal Function:
- Creatinine = 2.0 times ULN
12. Currently using a GnRH agonist or antagonist (unless surgically
castrated).

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 300
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 900

Exclusion Criteria

1. Cancer-related pain requiring scheduled opioid narcotics for control (as needed. = 2x per week is allowed).
2. Metastasis to organ systems other than lymph nodes and/or bone.
3. LDH = 2 times ULN.
4. Alkaline phosphatase = 2 times ULN.
5. Estimated PSA doubling time of <1 month as established within 6 months of the anticipated first dose of vaccine or placebo. A minimum of 3 PSA level determinations, at least 2 weeks apart (over a 6 month timeperiod), are required for assessment.
6. Concurrent or prior Provenge (sipuleucel-T) immunotherapy for prostate cancer
7. Receipt of an investigational agent within 30 days (or 60 days for an antibody-based therapy) of the first planned dose of PROSTVAC-V/F. There is no exclusion to previous experimental therapy provided dosing/treatment is completed at least 30 days prior to the first planned dose of vaccine unless otherwise noted.
8. History of prior malignancies other than prostate cancer within the past 3 years, excluding successfully resected basal or squamous cell carcinoma of the skin
9. Congestive heart failure (NYHA Class II, III, or IV), unstable angina, ventricular or hemodynamically significant atrial arrhythmia, or cardiovascular disease such as stroke or myocardial infarction (current or within the past 6 months).
10. Confirmed positive for HIV, hepatitis B, and /or hepatitis C.
11. Prior solid organ or bone marrow transplant
12. Immunodeficiency or splenectomy
13. Chronic immunosuppressive therapy within 30 days of screening.
14. Inflammatory eye disease requiring steroid treatment.
15. Chronic administration (defined as daily or every other day for continued use > 14 days) of systemic corticosteroids within 28 days of
the first planned dose of PROSTVAC-V/F. Use of inhaled steroids, nasal sprays, and topical creams for small body areas is allowed.
16. History of or active autoimmune disease (e.g. autoimmune neutropenia, thrombocytopenia, or hemolytic anemia, systemic lupus erythematosis, Sjogren?s syndrome, scleroderma, myasthenia gravis, Goodpasture?s syndrome, Addison?s disease, Hashimoto?s thyroiditis, or Graves disease). Persons with vitiligo are not excluded. Diabetics are not excluded if the condition is well controlled.
17. Known allergy to eggs, egg products, aminoglycoside antibiotics (for example, gentamicin or tobramycin), or GM-CSF. Subjects with a known or suspected allergy to radiological contrast agents are eligible, but this must be noted in the subject's medical history and in the chart notes.
18. History of atopic dermatitis or active skin condition (acute, chronic, exfoliative) that disrupts the epidermis.
19. Previous adverse reactions to smallpox vaccination.
20. Unable to avoid close contact or household contact with the following high-risk individuals for three to four weeks after the Day 1 vaccination or until the vaccination site heals completely: (a) children ? 3 years of age, (b) pregnant or nursing women, (c) individuals with prior or concurrent extensive eczema or other eczemoid skin disorders, or (d) immunocompromised individuals, such as those with HIV.
21. Significant medical abnormality (defined as a pre-existing condition AE/condition = Grade 3 according to NCI CTCAE v 4.0 and any condition which, in the opinion of the investigator, would prevent full participation in this trial (including the Long-Term Follow-Up), or would interfere with the evaluation of the trial endpoints.
22. Study personnel.