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.