Phase III Study of DCVAC/PCa Added to Standard Chemotherapy for Men With Metastatic Castration Resistant Prostate Cancer

Inclusion criteria:

Male 18 years and older.
Histologically or cytologically confirmed prostate adenocarcinoma.

Presence of skeletal, or soft-tissue/visceral/nodal metastases according to one of the following criteria:

Confirmed pathological fracture related to the disease OR
Confirmation of distant bone and/or soft-tissue and/or visceral metastases on CT or MRI scan or bone scintigraphy OR
Positive pathology report of metastatic lesion

Disease progression despite androgen-deprivation therapy (ADT) as indicated by:

Prostate-specific antigen (PSA) increase that is ≥ 2 ng/mL and ≥ 25% above the minimum PSA as reached during ADT or above the pre-treatment level, if no response was observed and which is confirmed by a second value 1 or more weeks later OR
Progression of measurable lymph nodes (short axis ≥ 15 mm) or visceral lesion measurable per RECIST v1.1 criteria, confirmation by an independent review facility (IRF) required OR
Two or more new lesions appearing on bone scan/imaging compared with a previous scan (confirmation by IRF required)
Maintenance of castrate conditions: patients, who have not had a surgical orchiectomy, must continue with hormone therapy with gonadotropin releasing hormone/ luteinizing hormone-releasing hormone (GnRH/LHRH) agonists or antagonists to reach levels of serum testosterone of ≤ 1.7 nmol/L (50 ng/dL). The duration of the castration period must be at least 4 months before screening as evidenced by combination of clinical/laboratory data (see section 6.8.1).

Laboratory criteria:

White blood cells (WBC) greater than 4,000/mm3 (4.0 x109/L)
Neutrophil count greater than 1,500/mm3 (1.5 x109/L).
Hemoglobin of at least 10 g/dL (100 g/L).
Platelet count of at least 100,000/mm3 (100 x 109/L).
Total bilirubin within normal limits (benign hereditary hyperbilirubinemias, e.g. Gilbert's syndrome, are permitted).
Serum alanine aminotransferase, aspartate aminotransferase, and creatinine < 1.5x times the upper limit of normal (ULN).
Life expectancy of at least 6 months based on Investigator's judgment.
Eastern Cooperative Oncology Group (ECOG) Performance status 0-2.
At least 4 weeks after surgery or radiotherapy before randomization.
A minimum of 28 days beyond initiation of bisphosphonate or denosumab therapy before randomization.
Recovery from primary local surgical treatment, radiotherapy or orchiectomy before randomization.
Signed informed consent including patient's ability to comprehend its contents.

Exclusion criteria:

Confirmed brain and/or leptomeningeal metastases (other visceral metastases are acceptable).
Current symptomatic spinal cord compression requiring surgery or radiation therapy.
Prior chemotherapy for prostate cancer.

Patient co-morbidities:

Subjects who are not indicated for chemotherapy treatment with first line Standard of Care chemotherapy (docetaxel and prednisone).
HIV positive, human T-lymphotropic virus positive.
Active hepatitis B (active hepatitis B), active hepatitis C (HCV), active syphilis.
Evidence of active bacterial, viral or fungal infection requiring systemic treatment.

Clinically significant cardiovascular disease including:

symptomatic congestive heart failure.
unstable angina pectoris.
serious cardiac arrhythmia requiring medication.
uncontrolled hypertension.
myocardial infarction or ventricular arrhythmia or stroke within a 6 months before screening, known left ventricular ejection fraction (LVEF) < 40% or serious cardiac conduction system disorders, if a pacemaker is not present.
Pleural and pericardial effusion of any NCI CTCAE grade.
Peripheral neuropathy having a NCI CTCAE ≥ grade 2.
History of malignant disease (with the exception of non-melanoma skin tumors) in the preceding five years.
Active autoimmune disease requiring treatment.
History of severe forms of primary immune deficiencies.
History of anaphylaxis or other serious reaction following vaccination.
Known hypersensitivity to any constituent of the DCVAC/PCa or placebo product.
Uncontrolled co-morbidities including, psychiatric or social conditions which, in the Investigator's opinion, would prevent participation in the trial.
Systemic corticosteroids at doses greater than 40 mg hydrocortisone daily or equivalent for any reason other than treatment of PCa within 6 months before randomization.
Ongoing systemic immunosuppressive therapy for any reason.
Treatment with anti-androgens, inhibitors of adrenal-produced androgens or other hormonal tumor-focused treatment performed on the day of randomization (except for GnRH/LHRH agonists or antagonists) to exclude possible anti-androgen withdrawal response. This criterion is not applicable to subjects who have never responded to anti-androgen treatment, as there is no risk of anti-androgen withdrawal response.
Treatment with immunotherapy against PCa within 6 months before randomization.
Treatment with radiopharmaceutical within 8 weeks before randomization.
Participation in a clinical trial using non-immunological experimental therapy within 4 weeks before randomization.
Participation in a clinical trial using immunological experimental therapy (e.g., monoclonal antibodies, cytokines or active cellular immunotherapies) within 6 months before randomization.
Refusal to sign the informed consent.