Phase III Study of DCVAC/PCa Added to Standard Chemotherapy for Men With Metastatic Castration Resistant Prostate Cancer
Condition: Metastatic Castration-resistant Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: DCVAC/PCa; Placebo
Intervention description: DCVAC/PCa concurrently with docetaxel plus prednisone every 3 weeks (± 7 days). DCVAC/PCa was administered at least 7 days before or and at least 7 days after the nearest chemotherapy (days 8-15 of chemotherapy cycles). After discontinuation of chemotherapy for any reason, each following dose of DCVAC/PCa was given every 4 weeks (-7/+14 days) for up to a total of 15 doses.; Placebo concurrently with docetaxel plus prednisone every 3 weeks (± 7 days). Placebo was administered at least 7 days before or and at least 7 days after the nearest chemotherapy (days 8-15 of chemotherapy cycles). After discontinuation of chemotherapy for any reason, each following dose of placebo was given every 4 weeks (-7/+14 days) for up to a total of 15 doses.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 1182.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Immunotherapy; Metastatic; Castration-resistant; Prostate cancer; Biological; Vaccine

Summary:

      The VIABLE study sought to confirm the hypothesis that the combination of docetaxel with
      DCVAC/PCa followed by a maintenance therapy with DCVAC/PCa would improve overall survival in
      patients with metastatic castration-resistant prostate cancer.
    

Eligibility criteria:

        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.