ot applicable

Recruitment & Eligibility

Status: ot Recruiting

Sex: Male

Target Recruitment: 200

Inclusion Criteria

1. Male, age =18 years
2. Histologically confirmed castrate-refractory metastatic adenocarcinoma of the prostate with progressive disease
- after surgical castration; or during androgen suppression therapy, including a gonadoptropinreleasing hormone (GNRH) agonist or antagonist
and
- after at least 1 second-line anti-hormonal manipulation (e.g. antiandrogen; including combined androgen blockade followed by antiandrogen withdrawal)
and
- a serum testosterone level of < 50 ng/dL or < 1.7 nmol/L.
Progression will be confirmed either
- radiologically (nodal or other soft tissue progression, appearance of 2 or more new lesions on bone scan - to be confirmed by other imaging if flare or trauma is suspected); or
- by 2 consecutive rises of PSA, measured at least 1 week apart, resulting at least in a 50% increase over the nadir and PSA > 2 ng/mL.
The last of these PSA values must have been measured within 2 months prior to start of screening and
- In patients having received initial combined androgen blockade or have shown a decline in PSA for =3 months after administration of an antiandrogen an antiandrogen withdrawal response must have been excluded after discontinuation of antiandrogen therapy (e.g. bicalutamide, flutamide or nilutamide) for at least 6 weeks prior to randomisation. Patients with a confirmed progression (PCWG2) after an antiandrogen withdrawal response are eligible. All patients must have discontinued antiandrogen treatment prior to randomization
3. Metastatic disease confirmed by imaging (bone scan, computed tomography [CT] or magnetic-resonance imaging [MRI]); ambiguous bone scan results should be confirmed by a second method.
4. Performance status: Eastern Cooperative Oncology Group (ECOG) 0 to 1.
5. Patients should be unlikely to need subsequent systemic therapy within the next 4 weeks (safety lead-in) or the next 3 months (randomised portion), in the opinion of the investigator.
6. Adequate organ function:
- Bone marrow function: haemoglobin =100 g/L; white blood cell count =3.0 × 1.000.000.000/L; lymphocyte count =0.8 × 1.000.000.000/L; absolute neutrophil count =1.5 × 1.000.000.000/L; platelet count =100 × 1.000.000.000/L.
- Hepatic: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =2.5 × upper limit of normal; bilirubin =1.5 × upper limit of normal.
- Renal: creatinine =2 mg/dL and creatinine clearance =45 mL/min/1.73m2.
7. Men of child producing potential must agree that together with their female partners they will use a highly effective method of contraception as defined in ICH (M3) resulting in a low failure rate (i.e. less than 1% per year) when used consistently and correctly. Those methods include
implants, injectables, combined oral contraceptives, some intrauterine devices (IUDs), sexual abstinence or vasectomy. The contraception should be applied until 1 month after the last vaccination.
8. Patients requiring bisphosphonates or denosumab at the time of registration into the trial are eligible as long as therapy is initiated at least 28 days prior to first study treatment administration and it must be continued during the study unless contraindications arise.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 50
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 150
;
1. Male, age =18 years
2. Histologically confirmed castrate-refractory metastatic adenocarcinoma of the prostate with progressive disease
- after surgical castration; or during androgen suppression therapy, including a gonadoptropinreleasing hormone (GNRH) agonist or antagonist
and
- after at least 1 second-line anti-hormonal manipulation (e.g. antiandrogen; including combined androgen blockade followed by antiandrogen withdrawal)
and
- a serum testosterone level of < 50 ng/dL or < 1.7 nmol/L.
Progression will be confirmed either
- radiologically (nodal or other soft tissue progression, appearance of 2 or more new lesions on bone scan - to be confirmed by other imaging if flare or trauma is suspected); or
- by 2 consecutive rises of PSA, measured at least 1 week apart, resulting at least in a 50% increase over the nadir and PSA > 2 ng/mL.
The last of these PSA values must have been measured within 2 months prior to start of screening and
- In patients having received initial combined androgen blockade or have shown a decline in PSA for =3 months after administration of an antiandrogen an antiandrogen withdrawal response must have been excluded after discontinuation of antiandrogen therapy (e.g. bicalutamide, flutamide or nilutamide) for at least 6 weeks prior to randomisation. Patients with a confirmed progression (PCWG2) after an antiandrogen withdrawal response are eligible. All patients must have discontinued antiandrogen treatment prior to randomization
3. Metastatic disease confirmed by imaging (bone scan, computed tomography [CT] or magnetic-resonance imaging [MRI]); ambiguous bone scan results should be confirmed by a second method.
4. Performance status: Eastern Cooperative Oncology Group (ECOG) 0 to 1.
5. Patients should be unlikely to need subsequent systemic therapy within the next 4 weeks (safety lead-in) or the next 3 months (randomised portion), in the opinion of the investigator.
6. Adequate organ function:
- Bone marrow function: haemoglobin =100 g/L; white blood cell count =3.0 × 1.000.000.000/L; lymphocyte count =0.8 × 1.000.000.000/L; absolute neutrophil count =1.5 × 1.000.000.000/L; platelet count =100 × 1.000.000.000/L.
- Hepatic: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =2.5 × upper limit of normal; bilirubin =1.5 × upper limit of normal.
- Renal: creatinine =2 mg/dL and creatinine clearance =45 mL/min/1.73m2.
7. Men of child producing potential must agree that together with their female partners they will use a highly effective method of contraception as defined in ICH (M3) resulting in a low failure rate (i.e. less than 1% per year) when used consistently and correctly. Those methods include
implants, injectables, combined oral contraceptives, some intrauterine devices (IUDs), sexual abstinence or vasectomy. The contraception should be applied until 1 month after the last vaccination.
8. Patients requiring bisphosphonates or denosumab at the time of registration into the trial are eligible as long as therapy is initiated at least 28 days prior to first study treatment administration and it must be continued during the study unless contraindications arise.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 50
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 150

Exclusion Criteria

1. Previous immunotherapy for PCA (e.g. sipuleucel-T [Provenge®], experimental cancer vaccines or ipilimumab [Yervoy®]).
2. Estimated life expectancy of < 6 months due to PCA or concomitant disease.
3. Treatment with any investigational anticancer agents within 4 weeks or 5 half-lives according to what gives the longer range prior to first dose of study drug.
4. Acute pathologic fracture or spinal cord compression at screening.
5. Systemic immunosuppressive agents including systemic steroids or immunomodulating agents including herbal remedies (e.g. mistletoe extract) for the previous 28 days prior to the start of treatment or need for such immunosuppressive/-modulating treatment, except glucocorticoid replacement therapy for adrenal insufficiency. For other conditions where steroid therapy is allowed, see section on prior and concomitant therapy (Section 6.3).
6. Active skin disease (atopic eczema, psoriasis) in the areas for vaccine injection (upper arms or thighs) preventing the administration of i.d. injections into areas of healthy skin.
7. Concurrent major surgery or planned surgery.
8. Prior splenectomy or prior allogeneic bone marrow transplant.
9. History of or current autoimmune disorders such as sarcoidosis, lupus erythematosus, rheumatoid arthritis, glomerulonephritis systemic vasculitis, autoimmune hepatitis, Sjögren syndrome, scleroderma, polymyalgia rheumatica, arteriitis temporalis, calcinosis, Raynauds
disease, esophageal dysmotility, sclerodactyly and telangiectasia (CREST) syndrome (limited cutaneous scleroderma), dermatomyositis, Morbus Crohn and colitis ulcerosa except autoimmune thyroiditis with only thyroid hormone replacement or vitiligo or Diabetes Mellitus type 1.
10. Primary or secondary immune deficiency.
11. Allergies to any components of the study drug including allergy to protamine sulfate (e.g. allergy to protaminecontaining insulins) or fish allergy.
12. Allergies to penicillins or other ß-lactam antibiotics
13. Active infections requiring anti-infectious therapy at the time of randomization.
14. Seropositive for human immunodeficiency virus, hepatitis B virus (except after hepatitis B vaccination) or hepatitis C virus infection.
15. Uncontrolled urinary retention or hydronephrosis (to be confirmed by ultrasound, bladder scan or other adequate imaging method). Patients with urinary retention can be enrolled after adequate
treatment, see section 6.3.
16. Uncontrolled medical condition considered as high risk for the treatment with an investigational drug (e.g. unstable Diabetes Mellitus, vena-cava-syndrome, uncontrolled pleural effusion, acute pulmonary embolism).
17. Known brain metastases or leptomeningeal involvement.
18. Symptomatic congestive heart failure (New York Heart Association 3 or 4), unstable angina pectoris or myocardial infarction, significant cardiac arrhythmia, history of stroke or transient ischemic attack, all within 6 months prior to enrolment or severe hypertension according to
WHO criteria or uncontrolled hypertension at the time of enrolment(systolic blood pressure =180 mm Hg).
19. History of seizures, encephalitis or multiple sclerosis.
20. Active drug abuse or chronic alcoholism.
21. Inability to provide informed consent due to mental impairment.
The following are additional exclusion criteria only for patients participating in the randomised part of the trial:
22. Previous chemotherapy for metastatic PCA.
23. Previous anti-hormonal treatment with abira;
1. Previous immunotherapy for PCA (e.g. sipuleucel-T [Provenge®], experimental cancer vaccines or ipilimumab [Yervoy®]).
2. Estimated life expectancy of < 6 months due to PCA or concomitant disease.
3. Treatment with any investigational anticancer agents within 4 weeks or 5 half-lives according to what gives the longer range prior to first dose of study drug.
4. Acute pathologic fracture or spinal cord compression at screening.
5. Systemic immunosuppressive agents including systemic steroids or immunomodulating agents including herbal remedies (e.g. mistletoe extract) for the previous 28 days prior to the start of treatment or need for such immunosuppressive/-modulating treatment, except glucocorticoid replacement therapy for adrenal insufficiency. For other conditions where steroid therapy is allowed, see section on prior and concomitant therapy (Section 6.3).
6. Active skin disease (atopic eczema, psoriasis) in the areas for vaccine injection (upper arms or thighs) preventing the administration of i.d. injections into areas of healthy skin.
7. Concurrent major surgery or planned surgery.
8. Prior splenectomy or prior allogeneic bone marrow transplant.
9. History of or current autoimmune disorders such as sarcoidosis, lupus erythematosus, rheumatoid arthritis, glomerulonephritis systemic vasculitis, autoimmune hepatitis, Sjögren syndrome, scleroderma, polymyalgia rheumatica, arteriitis temporalis, calcinosis, Raynauds
disease, esophageal dysmotility, sclerodactyly and telangiectasia (CREST) syndrome (limited cutaneous scleroderma), dermatomyositis, Morbus Crohn and colitis ulcerosa except autoimmune thyroiditis with only thyroid hormone replacement or vitiligo or Diabetes Mellitus type 1.
10. Primary or secondary immune deficiency.
11. Allergies to any components of the study drug including allergy to protamine sulfate (e.g. allergy to protaminecontaining insulins) or fish allergy.
12. Allergies to penicillins or other ß-lactam antibiotics
13. Active infections requiring anti-infectious therapy at the time of randomization.
14. Seropositive for human immunodeficiency virus, hepatitis B virus (except after hepatitis B vaccination) or hepatitis C virus infection.
15. Uncontrolled urinary retention or hydronephrosis (to be confirmed by ultrasound, bladder scan or other adequate imaging method). Patients with urinary retention can be enrolled after adequate
treatment, see section 6.3.
16. Uncontrolled medical condition considered as high risk for the treatment with an investigational drug (e.g. unstable Diabetes Mellitus, vena-cava-syndrome, uncontrolled pleural effusion, acute pulmonary embolism).
17. Known brain metastases or leptomeningeal involvement.
18. Symptomatic congestive heart failure (New York Heart Association 3 or 4), unstable angina pectoris or myocardial infarction, significant cardiac arrhythmia, history of stroke or transient ischemic attack, all within 6 months prior to enrolment or severe hypertension according to
WHO criteria or uncontrolled hypertension at the time of enrolment(systolic blood pressure =180 mm Hg).
19. History of seizures, encephalitis or multiple sclerosis.
20. Active drug abuse or chronic alcoholism.
21. Inability to provide informed consent due to mental impairment.
The following are additional exclusion criteria only for patients participating in the randomised part of the trial:
22. Previous chemotherapy for metastatic PCA.
23. Previous anti-hormonal treatment with abira;
1. Previous immunotherapy for PCA (e.g. sipuleucel-T [Provenge®], experimental cancer vaccines or ipilimumab [Yervoy®]).
2. Estimated life expectancy of < 6 months due to PCA or concomitant disease.
3. Treatment with any investigational anticancer agents within 4 weeks or 5 half-lives according to what gives the longer range prior to first dose of study drug.
4. Acute pathologic fracture or spinal cord compression at screening.
5. Systemic immunosuppressive agents including systemic steroids or immunomodulating agents including herbal remedies (e.g. mistletoe extract) for the previous 28 days prior to the start of treatment or need for such immunosuppressive/-modulating treatment, except glucocorticoid replacement therapy for adrenal insufficiency. For other conditions where steroid therapy is allowed, see section on prior and concomitant therapy (Section 6.3).
6. Active skin disease (atopic eczema, psoriasis) in the areas for vaccine injection (upper arms or thighs) preventing the administration of i.d. injections into areas of healthy skin.
7. Concurrent major surgery or planned surgery.
8. Prior splenectomy or prior allogeneic bone marrow transplant.
9. History of or current autoimmune disorders such as sarcoidosis, lupus erythematosus, rheumatoid arthritis, glomerulonephritis systemic vasculitis, autoimmune hepatitis, Sjögren syndrome, scleroderma, polymyalgia rheumatica, arteriitis temporalis, calcinosis, Raynauds
disease, esophageal dysmotility, sclerodactyly and telangiectasia (CREST) syndrome (limited cutaneous scleroderma), dermatomyositis, Morbus Crohn and colitis ulcerosa except autoimmune thyroiditis with only thyroid hormone replacement or vitiligo or Diabetes Mellitus type 1.
10. Primary or secondary immune deficiency.
11. Allergies to any components of the study drug including allergy to protamine sulfate (e.g. allergy to protaminecontaining insulins) or fish allergy.
12. Allergies to penicillins or other ß-lactam antibiotics
13. Active infections requiring anti-infectious therapy at the time of randomization.
14. Seropositive for human immunodeficiency virus, hepatitis B virus (except after hepatitis B vaccination) or hepatitis C virus infection.
15. Uncontrolled urinary retention or hydronephrosis (to be confirmed by ultrasound, bladder scan or other adequate imaging method). Patients with urinary retention can be enrolled after adequate
treatment, see section 6.3.
16. Uncontrolled medical condition considered as high risk for the treatment with an investigational drug (e.g. unstable Diabetes Mellitus, vena-cava-syndrome, uncontrolled pleural effusion, acute pulmonary embolism).
17. Known brain metastases or leptomeningeal involvement.
18. Symptomatic congestive heart failure (New York Heart Association 3 or 4), unstable angina pectoris or myocardial infarction, significant cardiac arrhythmia, history of stroke or transient ischemic attack, all within 6 months prior to enrolment or severe hypertension according to
WHO criteria or uncontrolled hypertension at the time of enrolment(systolic blood pressure =180 mm Hg).
19. History of seizures, encephalitis or multiple sclerosis.
20. Active drug abuse or chronic alcoholism.
21. Inability to provide informed consent due to mental impairment.
The following are additional exclusion criteria only for patients participating in the randomised part of the trial:
22. Previous chemotherapy for metastatic PCA.
23. Previous anti-hormonal treatment with abira