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

• ClinicalTrials.gov Identifier: NCT02111577
• Recruitment Status: Completed
• First Posted: April 11, 2014
• Results First Posted: April 6, 2021
• Last Update Posted: April 6, 2021
• Sponsor: Sotio a.s.
• Information provided by (Responsible Party): Sotio a.s.

Tracking Information

• First Submitted Date: April 9, 2014
• First Posted Date: April 11, 2014
• Results First Submitted Date: January 22, 2021
• Results First Posted Date: April 6, 2021
• Last Update Posted Date: April 6, 2021
• Actual Study Start Date: May 26, 2014
• Actual Primary Completion Date: January 28, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 10, 2021)

Overall Survival, Intention-to-treat Population [ Time Frame: From randomization to death due to any cause, up to 58 months ]

Overall survival is defined as the time from randomization until death due to any cause.

• Original Primary Outcome Measures (submitted: April 10, 2014): Overall survival (all cause mortality) [ Time Frame: 124 Weeks ]

Current Secondary Outcome Measures (submitted: March 10, 2021)

• Overall Survival, Per Protocol Population [ Time Frame: From randomization to death due to any cause, up to 58 months ]
  Overall survival is defined as the time from randomization until death due to any cause.
• Overall Survival, Intention-to-treat Population, Abiraterone as Prior Therapy [ Time Frame: From randomization to death due to any cause, up to 58 months ]
  Overall survival is defined as the time from randomization until death due to any cause.
• Overall Survival, Intention-to-treat Population, Enzalutamide as Prior Therapy [ Time Frame: From randomization to death due to any cause, up to 58 months ]
  Overall survival is defined as the time from randomization until death due to any cause.
• Overall Survival, Intention-to-treat Population, no Prior Abiraterone or Enzalutamide [ Time Frame: From randomization to death due to any cause, up to 58 months ]
  Overall survival is defined as the time from randomization until death due to any cause.
• Radiological Progression-free Survival, Intention-to-treat Population [ Time Frame: Time from randomization to the date of the earliest objective evidence of either radiographic progression of bone lesions, radiographic progression of soft tissue lesions, or death due to any cause, up to 58 months ]
  Progressive disease on bone scans was defined as a minimum of two new lesions. Visceral and nodal disease was evaluated according to RECIST 1.1 with modifications as described in the Statistical Analysis Plan.
• Radiological Progression-free Survival, Per Protocol Population [ Time Frame: Time from randomization to the date of the earliest objective evidence of either radiographic progression of bone lesions, radiographic progression of soft tissue lesions, or death due to any cause, up to 58 months ]
  Progressive disease on bone scans was defined as a minimum of two new lesions. Visceral and nodal disease was evaluated according to RECIST 1.1 with modifications as described in the Statistical Analysis Plan.
• Time to PSA Progression, Intention-to-treat Population [ Time Frame: Time from randomization to the date of objective evidence of PSA progression (PSA absolute increase ≥ 2 ng/mL and ≥ 25% above nadir or baseline values providing confirmation by a second consecutive value obtained at least 3 weeks later), up to 39 months ]
  The evidence of PSA progression is defined as: time from randomization to the date of PSA absolute increase ≥ 2 ng/mL and ≥ 25% above nadir or baseline values confirmed by a second consecutive value obtained at least 3 weeks later.
• Time to PSA Progression, Per Protocol Population [ Time Frame: Time from randomization to the date of objective evidence of PSA progression (PSA absolute increase ≥ 2 ng/mL and ≥ 25% above nadir or baseline values providing confirmation by a second consecutive value obtained at least 3 weeks later), up to 39 months ]
  The evidence of PSA progression is defined as: time from randomization to the date of PSA absolute increase ≥ 2 ng/mL and ≥ 25% above nadir or baseline values confirmed by a second consecutive value obtained at least 3 weeks later.
• Time to First Skeletal-related Event, Intention-to-treat Population [ Time Frame: Time from randomization to the date of the first skeletal-related event, up to 58 months ]
  Skeletal-related events included:

  • Radiation therapy to bone
  • Pathologic bone fracture
  • Spinal cord compression
  • Surgery to bone
  • Change in antineoplastic therapy to treat bone pain
• Time to First Skeletal-related Event, Per Protocol Population [ Time Frame: Time from randomization to the date of the first skeletal-related event, up to 58 months ]
  Skeletal-related events included:

  • Radiation therapy to bone
  • Pathologic bone fracture
  • Spinal cord compression
  • Surgery to bone
  • Change in antineoplastic therapy to treat bone pain
• Time to Radiological Progression or Skeletal-related Event, Intention-to-treat Population [ Time Frame: Time from randomization to the date of the first radiological progression or skeletal-related event, up to 58 months ]
  Progressive disease on bone scans defined as a minimum of two new lesions. Visceral and nodal disease was evaluated according to RECIST 1.1 with modifications as described in the Statistical Analysis Plan. Skeletal-related events included:

  • Radiation therapy to bone
  • Pathologic bone fracture
  • Spinal cord compression
  • Surgery to bone
  • Change in antineoplastic therapy to treat bone pain
• Time to Radiological Progression or Skeletal-related Event, Per Protocol Population [ Time Frame: Time from randomization to the date of the first radiological progression or skeletal-related event, up to 58 months ]
  Progressive disease on bone scans defined as a minimum of two new lesions. Visceral and nodal disease was evaluated according to RECIST 1.1 with modifications as described in the Statistical Analysis Plan. Skeletal-related events included:

  • Radiation therapy to bone
  • Pathologic bone fracture
  • Spinal cord compression
  • Surgery to bone
  • Change in antineoplastic therapy to treat bone pain
• Proportion of Patients With Skeletal-related Events, Intention-to-treat Population [ Time Frame: From randomization to the end of the study, up to 57 months ]
  Progressive disease on bone scans defined as a minimum of two new lesions. Visceral and nodal disease was evaluated according to RECIST 1.1 with modifications as described in the Statistical Analysis Plan. Skeletal-related events included:

  • Radiation therapy to bone
  • Pathologic bone fracture
  • Spinal cord compression
  • Surgery to bone
  • Change in antineoplastic therapy to treat bone pain
• Proportion of Patients With Skeletal-related Events, Per Protocol Population [ Time Frame: From randomization to the end of the study, up to 57 months ]
  Progressive disease on bone scans defined as a minimum of two new lesions. Visceral and nodal disease was evaluated according to RECIST 1.1 with modifications as described in the Statistical Analysis Plan. Skeletal-related events included:

  • Radiation therapy to bone
  • Pathologic bone fracture
  • Spinal cord compression
  • Surgery to bone
  • Change in antineoplastic therapy to treat bone pain

Original Secondary Outcome Measures (submitted: April 10, 2014)

• Radiographic Progression Free Survival [ Time Frame: 0, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120 weeks ]
• Duration to Prostate Specific Antigen (PSA) Progression [ Time Frame: 0, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120 weeks ]
• Duration to Skeletal Related Events [ Time Frame: 0, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 34, 38, 42, 46, 50, 54, 66, 78, 90, 102, 124 weeks ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Phase III Study of DCVAC/PCa Added to Standard Chemotherapy for Men With Metastatic Castration Resistant Prostate Cancer
• Official Title: A Randomized, Double Blind, Multicenter, Parallel-group, Phase III Study to Evaluate Efficacy and Safety of DCVAC/PCa Versus Placebo in Men With Metastatic Castration Resistant Prostate Cancer Eligible for 1st Line Chemotherapy
• Brief 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.
• Detailed Description: This was a randomized, double blind, placebo-controlled, multicenter, international, parallel-group phase III study. Patients with metastatic castration-resistant prostate cancer who were candidates to receive standard of care first-line chemotherapy with docetaxel plus prednisone were randomized 2:1 into one of two arms: an investigational arm (DCVAC/PCa) and a control arm (placebo) in addition to chemotherapy (docetaxel plus prednisone).
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Metastatic Castration-resistant Prostate Cancer

Intervention

• Biological: DCVAC/PCa
  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.
  Other Name: Stapuldencel
• Biological: Placebo
  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.

Study Arms

• Experimental: DCVAC/PCa with standard of care chemotherapy
  Combination therapy with DCVAC/PCa and standard of care chemotherapy (docetaxel and prednisone)
  Intervention: Biological: DCVAC/PCa
• Placebo Comparator: Placebo with standard of care chemotherapy
  Combination therapy with placebo and standard of care chemotherapy (docetaxel and prednisone) as comparator
  Intervention: Biological: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 25, 2020): 1182
• Original Estimated Enrollment (submitted: April 10, 2014): 1170
• Actual Study Completion Date: January 28, 2020
• Actual Primary Completion Date: January 28, 2020 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Austria, Belarus, Belgium, Bulgaria, Croatia, Czechia, Denmark, France, Germany, Hungary, Italy, Latvia, Lithuania, Netherlands, Poland, Portugal, Serbia, Slovakia, Spain, Sweden, United Kingdom, United States
• Removed Location Countries: Czech Republic, Romania, Turkey

Administrative Information

• NCT Number: NCT02111577
• Other Study ID Numbers: SP005; 2012-002814-38 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Sotio a.s.
• Study Sponsor: Sotio a.s.
• Collaborators: Not Provided

Investigators

• Principal Investigator: Nicholas J. Vogelzang; US Oncology Research/Comprehensive Cancer Centers of Nevada

• PRS Account: Sotio a.s.
• Verification Date: March 2021