Metastatic Castration-resistant Prostate Cancer
Conditions
Keywords
Immunotherapy, Metastatic, Castration-resistant, Prostate cancer, Biological, Vaccine
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).
Interventions
BIOLOGICALDCVAC/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.
BIOLOGICALPlacebo
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.
Sponsors
SOTIO a.s.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival, Intention-to-treat Population | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival, Intention-to-treat Population, Abiraterone as Prior Therapy | 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 | 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 | 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 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 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 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. |
| Overall Survival, Per Protocol Population | 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. |
| Time to First Skeletal-related Event, Intention-to-treat Population | 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 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 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 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 | 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 | 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 |
| Time to PSA Progression, Per Protocol Population | 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. |
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
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| DCVAC/PCa With Standard of Care Chemotherapy Combination therapy with DCVAC/PCa and standard of care chemotherapy (docetaxel and prednisone) | 787 |
| Placebo With Standard of Care Chemotherapy Combination therapy with placebo and standard of care chemotherapy (docetaxel and prednisone) as comparator | 395 |
| Total | 1,182 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Death | 518 | 254 |
| Overall Study | Disease progression | 0 | 1 |
| Overall Study | Failure to produce study treatment | 6 | 0 |
| Overall Study | Lost to Follow-up | 19 | 10 |
| Overall Study | Medical monitor's decision (active hepatitis B) | 1 | 0 |
| Overall Study | Protocol Violation | 2 | 0 |
| Overall Study | Unable to tolerate leukapheresis | 1 | 0 |
| Overall Study | Withdrawal by Subject | 51 | 23 |
Baseline characteristics
| Characteristic | DCVAC/PCa With Standard of Care Chemotherapy | Placebo With Standard of Care Chemotherapy | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 515 Participants | 288 Participants | 803 Participants |
| Age, Categorical Between 18 and 65 years | 272 Participants | 107 Participants | 379 Participants |
| Age, Continuous | 68.0 years | 69.0 years | 68.0 years |
| Prostate-specific antigen | 46.35 ng/L | 54.02 ng/L | 47.87 ng/L |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 4 Participants | 9 Participants |
| Race (NIH/OMB) Black or African American | 26 Participants | 19 Participants | 45 Participants |
| Race (NIH/OMB) More than one race | 4 Participants | 3 Participants | 7 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 18 Participants | 11 Participants | 29 Participants |
| Race (NIH/OMB) White | 733 Participants | 358 Participants | 1091 Participants |
| Region of Enrollment Austria | 14 participants | 5 participants | 19 participants |
| Region of Enrollment Belarus | 13 participants | 18 participants | 31 participants |
| Region of Enrollment Belgium | 20 participants | 11 participants | 31 participants |
| Region of Enrollment Bulgaria | 15 participants | 10 participants | 25 participants |
| Region of Enrollment Croatia | 18 participants | 6 participants | 24 participants |
| Region of Enrollment Czechia | 102 participants | 40 participants | 142 participants |
| Region of Enrollment Denmark | 2 participants | 0 participants | 2 participants |
| Region of Enrollment France | 18 participants | 12 participants | 30 participants |
| Region of Enrollment Germany | 92 participants | 51 participants | 143 participants |
| Region of Enrollment Hungary | 28 participants | 14 participants | 42 participants |
| Region of Enrollment Italy | 19 participants | 3 participants | 22 participants |
| Region of Enrollment Latvia | 0 participants | 2 participants | 2 participants |
| Region of Enrollment Lithuania | 6 participants | 5 participants | 11 participants |
| Region of Enrollment Netherlands | 29 participants | 19 participants | 48 participants |
| Region of Enrollment Poland | 94 participants | 36 participants | 130 participants |
| Region of Enrollment Portugal | 20 participants | 10 participants | 30 participants |
| Region of Enrollment Serbia | 22 participants | 14 participants | 36 participants |
| Region of Enrollment Slovakia | 49 participants | 15 participants | 64 participants |
| Region of Enrollment Spain | 18 participants | 14 participants | 32 participants |
| Region of Enrollment Sweden | 4 participants | 1 participants | 5 participants |
| Region of Enrollment United Kingdom | 60 participants | 36 participants | 96 participants |
| Region of Enrollment United States | 144 participants | 73 participants | 217 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 787 Participants | 395 Participants | 1182 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 518 / 787 | 254 / 395 |
| other Total, other adverse events | 670 / 749 | 365 / 379 |
| serious Total, serious adverse events | 237 / 749 | 150 / 379 |
Outcome results
Primary
Overall Survival, Intention-to-treat Population
Overall survival is defined as the time from randomization until death due to any cause.
Time frame: From randomization to death due to any cause, up to 58 months
Population: Intention-to-treat population definition: All randomized patients
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DCVAC/PCa With Standard of Care Chemotherapy | Overall Survival, Intention-to-treat Population | 23.9 Months |
| Placebo With Standard of Care Chemotherapy | Overall Survival, Intention-to-treat Population | 24.3 Months |
Comparison: Stratifiedp-value: 0.59695% CI: [0.895, 1.213]Log Rank
Comparison: Unstratifiedp-value: 0.64895% CI: [0.891, 1.204]Log Rank
Secondary
Overall Survival, Intention-to-treat Population, Abiraterone as Prior Therapy
Overall survival is defined as the time from randomization until death due to any cause.
Time frame: From randomization to death due to any cause, up to 58 months
Population: Intention-to-treat population definition: All randomized patients with abiraterone as prior therapy
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DCVAC/PCa With Standard of Care Chemotherapy | Overall Survival, Intention-to-treat Population, Abiraterone as Prior Therapy | 16.6 Months |
| Placebo With Standard of Care Chemotherapy | Overall Survival, Intention-to-treat Population, Abiraterone as Prior Therapy | 21.0 Months |
Comparison: Stratifiedp-value: 0.07195% CI: [0.976, 1.762]Log Rank
Comparison: Unstratifiedp-value: 0.0995% CI: [0.961, 1.712]Log Rank
Secondary
Overall Survival, Intention-to-treat Population, Enzalutamide as Prior Therapy
Overall survival is defined as the time from randomization until death due to any cause.
Time frame: From randomization to death due to any cause, up to 58 months
Population: Intention-to-treat population definition: All randomized patients with enzalutamide as prior therapy
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DCVAC/PCa With Standard of Care Chemotherapy | Overall Survival, Intention-to-treat Population, Enzalutamide as Prior Therapy | 15.2 Months |
| Placebo With Standard of Care Chemotherapy | Overall Survival, Intention-to-treat Population, Enzalutamide as Prior Therapy | 21.4 Months |
Comparison: Stratifiedp-value: 0.04995% CI: [1, 2.134]Log Rank
Comparison: Unstratifiedp-value: 0.05395% CI: [0.993, 2.077]Log Rank
Secondary
Overall Survival, Intention-to-treat Population, no Prior Abiraterone or Enzalutamide
Overall survival is defined as the time from randomization until death due to any cause.
Time frame: From randomization to death due to any cause, up to 58 months
Population: Intention-to-treat population definition: All randomized patients with neither abiraterone nor enzalutamide as prior therapy
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DCVAC/PCa With Standard of Care Chemotherapy | Overall Survival, Intention-to-treat Population, no Prior Abiraterone or Enzalutamide | 26.7 Months |
| Placebo With Standard of Care Chemotherapy | Overall Survival, Intention-to-treat Population, no Prior Abiraterone or Enzalutamide | 25.7 Months |
Comparison: Stratifiedp-value: 0.50195% CI: [0.779, 1.13]Log Rank
Comparison: Unstratifiedp-value: 0.51295% CI: [0.781, 1.131]Log Rank
Secondary
Overall Survival, Per Protocol Population
Overall survival is defined as the time from randomization until death due to any cause.
Time frame: From randomization to death due to any cause, up to 58 months
Population: Per protocol population definition:~A subset of all randomized patients characterized by the following criteria:~* had at least 1 post-baseline efficacy assessment~* did not have any major protocol violation that would affect the endpoints being assessed~* received at least 8 doses of DCVAC/PCa or placebo
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DCVAC/PCa With Standard of Care Chemotherapy | Overall Survival, Per Protocol Population | 29.7 Months |
| Placebo With Standard of Care Chemotherapy | Overall Survival, Per Protocol Population | 26.7 Months |
Comparison: Stratifiedp-value: 0.33595% CI: [0.746, 1.105]Log Rank
Comparison: Unstratifiedp-value: 0.19295% CI: [0.725, 1.067]Log Rank
Secondary
Proportion of Patients With Skeletal-related Events, Intention-to-treat Population
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 frame: From randomization to the end of the study, up to 57 months
Population: Intention-to-treat population definition: All randomized patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DCVAC/PCa With Standard of Care Chemotherapy | Proportion of Patients With Skeletal-related Events, Intention-to-treat Population | 43 Patients |
| Placebo With Standard of Care Chemotherapy | Proportion of Patients With Skeletal-related Events, Intention-to-treat Population | 26 Patients |
Comparison: Stratifiedp-value: 0.48595% CI: [0.528, 1.355]Log binomial model
Secondary
Proportion of Patients With Skeletal-related Events, Per Protocol Population
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 frame: From randomization to the end of the study, up to 57 months
Population: A subset of all randomized patients characterized by the following criteria:~* had at least 1 post-baseline efficacy assessment~* did not have any major protocol violation that would affect the endpoints being assessed~* received at least 8 doses of DCVAC/PCa or placebo
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DCVAC/PCa With Standard of Care Chemotherapy | Proportion of Patients With Skeletal-related Events, Per Protocol Population | 28 Patients |
| Placebo With Standard of Care Chemotherapy | Proportion of Patients With Skeletal-related Events, Per Protocol Population | 20 Patients |
Comparison: Stratifiedp-value: 0.76895% CI: [0.529, 1.601]Log binomial model
Secondary
Radiological Progression-free Survival, Intention-to-treat Population
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 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
Population: Intention-to-treat population definition: All randomized patients
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DCVAC/PCa With Standard of Care Chemotherapy | Radiological Progression-free Survival, Intention-to-treat Population | 11.1 Months |
| Placebo With Standard of Care Chemotherapy | Radiological Progression-free Survival, Intention-to-treat Population | 11.1 Months |
Comparison: Stratifiedp-value: 0.88695% CI: [0.863, 1.136]Log Rank
Comparison: Unstratifiedp-value: 0.99295% CI: [0.875, 1.145]Log Rank
Secondary
Radiological Progression-free Survival, Per Protocol Population
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 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
Population: Per protocol population definition:~A subset of all randomized patients characterized by the following criteria:~* had at least 1 post-baseline efficacy assessment~* did not have any major protocol violation that would affect the endpoints being assessed~* received at least 8 doses of DCVAC/PCa or placebo
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DCVAC/PCa With Standard of Care Chemotherapy | Radiological Progression-free Survival, Per Protocol Population | 11.2 Months |
| Placebo With Standard of Care Chemotherapy | Radiological Progression-free Survival, Per Protocol Population | 11.2 Months |
Comparison: Stratifiedp-value: 0.99495% CI: [0.847, 1.184]Log Rank
Comparison: Unstratifiedp-value: 0.98295% CI: [0.851, 1.18]Log Rank
Secondary
Time to First Skeletal-related Event, Intention-to-treat Population
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 frame: Time from randomization to the date of the first skeletal-related event, up to 58 months
Population: Intention-to-treat population definition: All randomized patients
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DCVAC/PCa With Standard of Care Chemotherapy | Time to First Skeletal-related Event, Intention-to-treat Population | NA Months |
| Placebo With Standard of Care Chemotherapy | Time to First Skeletal-related Event, Intention-to-treat Population | NA Months |
Comparison: Stratifiedp-value: 0.73295% CI: [0.563, 1.497]Log Rank
Comparison: Unstratifiedp-value: 0.71395% CI: [0.561, 1.485]Log Rank
Secondary
Time to First Skeletal-related Event, Per Protocol Population
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 frame: Time from randomization to the date of the first skeletal-related event, up to 58 months
Population: Per protocol population definition:~A subset of all randomized patients characterized by the following criteria:~* had at least 1 post-baseline efficacy assessment~* did not have any major protocol violation that would affect the endpoints being assessed~* received at least 8 doses of DCVAC/PCa or placebo
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DCVAC/PCa With Standard of Care Chemotherapy | Time to First Skeletal-related Event, Per Protocol Population | NA Months |
| Placebo With Standard of Care Chemotherapy | Time to First Skeletal-related Event, Per Protocol Population | NA Months |
Comparison: Stratifiedp-value: 0.69495% CI: [0.5, 1.587]Log Rank
Comparison: Unstratifiedp-value: 0.66195% CI: [0.496, 1.562]Log Rank
Secondary
Time to PSA Progression, Intention-to-treat Population
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 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
Population: Intention-to-treat population definition: All randomized patients
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DCVAC/PCa With Standard of Care Chemotherapy | Time to PSA Progression, Intention-to-treat Population | 10.5 Months |
| Placebo With Standard of Care Chemotherapy | Time to PSA Progression, Intention-to-treat Population | 10.6 Months |
Comparison: Stratifiedp-value: 0.39295% CI: [0.909, 1.277]Log Rank
Comparison: Unstratifiedp-value: 0.43995% CI: [0.905, 1.262]Log Rank
Secondary
Time to PSA Progression, Per Protocol Population
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 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
Population: Per protocol population definition:~A subset of all randomized patients characterized by the following criteria:~* had at least 1 post-baseline efficacy assessment~* did not have any major protocol violation that would affect the endpoints being assessed~* received at least 8 doses of DCVAC/PCa or placebo
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DCVAC/PCa With Standard of Care Chemotherapy | Time to PSA Progression, Per Protocol Population | 10.5 Months |
| Placebo With Standard of Care Chemotherapy | Time to PSA Progression, Per Protocol Population | 10.6 Months |
Comparison: Stratifiedp-value: 0.75495% CI: [0.857, 1.238]Log Rank
Comparison: Unstratifiedp-value: 0.92495% CI: [0.844, 1.207]Log Rank
Secondary
Time to Radiological Progression or Skeletal-related Event, Intention-to-treat Population
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 frame: Time from randomization to the date of the first radiological progression or skeletal-related event, up to 58 months
Population: Intention-to-treat population definition: All randomized patients
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DCVAC/PCa With Standard of Care Chemotherapy | Time to Radiological Progression or Skeletal-related Event, Intention-to-treat Population | 11.1 Months |
| Placebo With Standard of Care Chemotherapy | Time to Radiological Progression or Skeletal-related Event, Intention-to-treat Population | 10.9 Months |
Comparison: Stratifiedp-value: 0.11195% CI: [0.781, 1.027]Log Rank
Comparison: Unstratifiedp-value: 0.18495% CI: [0.798, 1.044]Log Rank
Secondary
Time to Radiological Progression or Skeletal-related Event, Per Protocol Population
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 frame: Time from randomization to the date of the first radiological progression or skeletal-related event, up to 58 months
Population: A subset of all randomized patients characterized by the following criteria:~* had at least 1 post-baseline efficacy assessment~* did not have any major protocol violation that would affect the endpoints being assessed~* received at least 8 doses of DCVAC/PCa or placebo
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DCVAC/PCa With Standard of Care Chemotherapy | Time to Radiological Progression or Skeletal-related Event, Per Protocol Population | 11.1 Months |
| Placebo With Standard of Care Chemotherapy | Time to Radiological Progression or Skeletal-related Event, Per Protocol Population | 11.1 Months |
Comparison: Stratifiedp-value: 0.4695% CI: [0.795, 1.11]Log Rank
Comparison: Unstratifiedp-value: 0.53495% CI: [0.807, 1.118]Log Rank