Prostate Cancer Metastatic
Conditions
Keywords
Asymptomatic, mildly symptomatic, metastatic castrate-resistant prostate cancer, mCRPC
Brief summary
The primary objective of the trial is to evaluate the clinical anti-tumor activity of EMD 525797 administered as 1-hour intravenous infusion every 3 weeks in terms of progression free survival (PFS) time in subjects with asymptomatic or mildly symptomatic metastatic castrate-resistant prostate cancer (mCRPC).
Interventions
DRUGEMD 525797
Subjects will be administered with EMD 525797 at a dose of 1500 milligram (mg) (diluted with 0.9 percent \[%\] sodium chloride) as a 1-hour intravenous infusion every 3 Weeks until disease progression or unacceptable toxicity, whichever comes first, unless the subject stopped the trial treatment for other reasons.
OTHERPlacebo
Subjects will be administered with placebo (as 0.9% sodium chloride) as a 1-hour intravenous infusion every 3 Weeks until disease progression or unacceptable toxicity, whichever comes first, unless the subject stopped the trial treatment for other reasons.
OTHERStandard of Care (SoC)
All the subjects followed the SoC consisting of the continued treatment with luteinizing-hormone releasing hormone agonists (or antagonists).
Sponsors
EMD Serono
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed adenocarcinoma of the prostate (Gleason score) * Bisphosphonate treatment * Stable, ongoing adequate testosterone suppression proven by hypogonadal levels of testosterone (less than or equal to) \<= 50 nanogram per deciliter \[ng/dL\]) for subjects without surgical castration (luteinizing hormone-releasing hormone antagonists and agonists) * Other protocol defined inclusion criteria could apply
Exclusion criteria
* Prior chemotherapy, biologic therapy (targeted therapy), or any experimental therapy for mCRPC * Chronic and ongoing treatment with opioids * Acute pathologic fracture, spinal cord compression, or hypercalcemia at Screening * Visceral metastasis, brain metastasis * Radiotherapy to bone lesions and/or orthopedic surgery for pathologic fractures. Any kinds of major elective surgery within 30 days prior to trial treatment * Other protocol defined
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) Time | Time from randomization until data cut-off date (30 April 2013), assessed up to 2 years | PFS was defined as time from randomization until the first documented sign of objective radiographic disease progression (ORDP) or death from any cause. Death was considered as an event only if it was reported within 12 weeks after last tumor assessment without progression. ORDP was defined as: Bone lesion progression (2 or more new bone lesions compared to baseline) assessed with bone scintigraphy. Assessment was based on Response Evaluation Criteria in Solid Tumors version 1.0 (RECIST v1.0) modified as per Prostate Cancer Working Group 2 (PCWG-2); Soft-tissue lesion progression assessed with CT scans according to RECIST v1.0 modified as per PCWG-2; Presence of skeletal events defined as cord compression/fracture documented via a scheduled or unscheduled radiographic assessment triggered by increased pain or other signs and/or symptoms, based on the investigator's discretion; Non-radiological events, including emergency bone irradiation and surgery, were not investigated. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | Time from randomization until data cut-off date (30 April 2013), assessed up to 2 years | Overall Survival was defined as the time from the date of randomization to the date of death from any cause. |
| Minimum Percentage Change From Baseline in PSA Serum Concentration | Baseline, up to data cut-off date (30 April 2013), assessed up to 2 years | — |
| Time to Tumor Progression | Time from randomization until data cut-off date (30 April 2013), assessed up to 2 years | Time to tumor progression was defined as the time from the date of randomization to the date of ORDP. ORDP was defined as: Bone lesion progression (2 or more new bone lesions compared to baseline) assessed with bone scintigraphy, which had to be confirmed by bone scintigraphy 6 weeks later if subjects remained asymptomatic or mildly symptomatic. Assessments were to be based on RECIST v1.0 modified according to PCWG-2; Soft-tissue lesion progression assessed with CT scans according to RECIST v1.0 modified as per PCWG-2; Presence of skeletal events defined as cord compression or fracture documented via a scheduled or unscheduled radiographic assessment triggered by increased pain or other signs and/or symptoms, based on the investigator's discretion; Non-radiological events, including emergency bone irradiation and surgery, were not investigated. |
| Number of Subjects With Presence of Tumor Response and Disease Control (DC) in Soft Tissue Lesions | Time from randomization until data cut-off date (30 April 2013), assessed up to 2 years | Presence of tumor response in soft tissue lesions was defined as the presence of at least 1 confirmed complete response (CR) or confirmed partial response (PR) in soft tissue lesions, documented by computed tomography (CT) scans. Presence of DC in soft tissue lesions was defined as the presence of at least 1 confirmed CR or confirmed PR or stable disease (SD) lasting at least 12 weeks after randomization. Tumor response assessments were based on RECIST v1.0 modified according to the PCWG-2. The response was evaluated for subjects with measurable disease at baseline. According to RECIST v1.0, CR=disappearance of all target and non-target lesions; PR=at least 30% decrease in the sum of the longest diameter of target lesions and non-complete response/non-progressive disease in non-target lesions. |
| Number of Subjects With New Bone Lesions Compared to Baseline | Time from randomization until data cut-off date (30 April 2013), assessed up to 2 years | New bone lesions were evaluated by bone scintigraphy for subjects with bone lesions at baseline. |
| Number of Subjects With Presence of DC in Bone Lesions | At Weeks 13, 19 and 25 | Presence of DC in bone lesions was defined as the appearance of less than 2 new bone lesions, documented by bone scintigraphy. |
| Bone and Soft Tissue Lesions Composite Tumor Response | Time from randomization until data cut-off date (30 April 2013), assessed up to 2 years | Bone and soft tissue lesions composite tumor response was defined as the presence of both a confirmed CR or PR, documented by CT scans, and a DC in bone lesions, documented by bone scintigraphy. CR was defined as disappearance of all target and non-target lesions and PR was defined as at least 30% decrease in the sum of the longest diameter of target lesions and non-complete response/non-progressive disease in non-target lesions. Presence of DC in bone lesions was defined as the appearance of less than 2 new bone lesions. |
| Number of Subjects With Presence of Prostate Specific Antigen (PSA) Response | Time from randomization until data cut-off date (30 April 2013), assessed up to 2 years | PSA response was defined as a decrease greater than 50 percent (%) in PSA value from baseline for 2 consecutive evaluations greater than or equal to (\>=) 3 Weeks apart. |
| Minimum Percentage Change From Baseline in the Number of Circulating Tumor Cells (CTCs) | Time from randomization until data cut-off date (30 April 2013), assessed up to 2 years | — |
| Overall Minimum Percentage Change From Previous Time Point in Circulating Tumor Cells (CTC) | Cycle 1, Day 1 (Week 1): pre-dose, Cycle 3, Day 1 (Week 7): pre-dose, and Cycle 5, Day 1 (Week 13): pre-dose | — |
| Number of Subjects With Any Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, and TEAEs Leading to Discontinuation | From the first dose of study drug administration until 50 days after the last dose of study drug administration or until cut-off date (30 April 2013), assessed up to 2 years | An AE was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. A serious adverse event was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAEs were defined as those AEs that started between first dose of study drug and up to 50 days after last dose. |
| Pharmacokinetic Parameter: Clearance of Intravenously Administered EMD 525797 After First Dose (CL) and Clearance in Steady State of EMD52597 After Fifth Dose (CLss) | Cycle 1 (Week 1) and cycle 5 (Week 13): Day 1: pre-dose, End of Infusion (EOI), 4, 8, 24, 48, 96, 168, 336, and 504 hours after start of infusion; Cycles 3 and 4 (Weeks 7 and 10), Day 1: pre-dose; Cycle 7 (Week 19), Day 1: pre-dose and EOI | The apparent total body clearance of drug following intravenous administration (CL); The apparent total body clearance of drug at steady state following intravenous administration (CLss). |
| Pharmacokinetic Parameter: Volume of Distribution of EMD 525797 After the First Dose (V) and in Steady State After the Fifth Dose (Vss) of Intravenous Infusion | Cycle 1 (Week 1) and cycle 5 (Week 13): Day 1: pre-dose, End of Infusion (EOI), 4, 8, 24, 48, 96, 168, 336, and 504 hours after start of infusion; Cycles 3 and 4 (Weeks 7 and 10), Day 1: pre-dose; Cycle 7 (Week 19), Day 1: pre-dose and EOI | The apparent volume of distribution during the terminal phase following intravenous administration (V). The estimate of the apparent volume of distribution at steady state following intravenous administration (Vss). |
| Number of Subjects With Presence of Skeletal Related Events | Time from randomization until data cut-off date (30 April 2013), assessed up to 2 years | Presence of skeletal related events was defined as cord compression or fracture documented via a scheduled or unscheduled radiographic assessment triggered by increased pain or other signs and/or symptoms at the investigator discretion. Non-radiological events, including emergency bone irradiation and surgery, were not investigated. |
Other
| Measure | Time frame |
|---|---|
| To Explore the Relationship Between Number and/or Changes of Numbers of Biomarker and the Clinical Outcome | From the date of randomization up to data cut-off date (30 April 2013), assessed up to 2 years |
Countries
Australia, Belgium, Canada, France, Germany, Netherlands, Poland, Russia, Slovakia, South Africa, Spain, United States
Participant flow
Recruitment details
First/Last subject (informed consent): April 2011/December 2012. Study completion date: July 2014. Clinical data cut-off: 30 April 2013. Subjects were recruited in 11 countries (Australia, Belgium, Canada, France, Germany, Netherlands, Poland, Russia, South Africa, Spain, and USA) across the globe in 65 centers.
Pre-assignment details
Enrolled: 283 screened for eligibility; 103 were excluded (mainly non-fulfillment of inclusion or exclusion criteria). 180 subjects were assigned to the treatment groups. Two subjects did not receive study drug administration.
Participants by arm
| Arm | Count |
|---|---|
| Placebo + SoC Subjects were administered with placebo 0.9% sodium chloride as a 1-hour intravenous infusion every 3 Weeks until disease progression or unacceptable toxicity, whichever comes first, unless the subject stopped the trial treatment for other reasons. All the subjects followed the SoC consisting of the continued treatment with luteinizing-hormone releasing hormone agonists (or antagonists). In order to avoid any confounding effects, bisphosphonate treatment was initiated 2 days before start of treatment with EMD 525797. | 60 |
| EMD 525797 750 mg + SoC Subjects were administered with EMD 525797 at a dose of 750 mg (diluted with 0.9% sodium chloride) as a 1-hour intravenous infusion every 3 Weeks until disease progression or unacceptable toxicity, whichever comes first, unless the subject stopped the trial treatment for other reasons. All the subjects followed the SoC consisting of the continued treatment with luteinizing-hormone releasing hormone agonists (or antagonists). In order to avoid any confounding effects, bisphosphonate treatment was initiated 2 days before start of treatment with EMD 525797. | 60 |
| EMD 525797 1500 mg + SoC Subjects were administered with EMD 525797 at a dose of 1500 mg (diluted with 0.9% sodium chloride) as a 1-hour intravenous infusion every 3 Weeks until disease progression or unacceptable toxicity, whichever comes first, unless the subject stopped the trial treatment for other reasons. All the subjects followed the SoC consisting of the continued treatment with luteinizing-hormone releasing hormone agonists (or antagonists). In order to avoid any confounding effects, bisphosphonate treatment was initiated 2 days before start of treatment with EMD 525797. | 60 |
| Total | 180 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Ongoing at data cut-off | 10 | 10 | 9 |
Baseline characteristics
| Characteristic | EMD 525797 1500 mg + SoC | Placebo + SoC | EMD 525797 750 mg + SoC | Total |
|---|---|---|---|---|
| Age, Continuous | 70.0 years STANDARD_DEVIATION 8.88 | 69.9 years STANDARD_DEVIATION 8.43 | 69.0 years STANDARD_DEVIATION 7.31 | 69.6 years STANDARD_DEVIATION 8.2 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 60 Participants | 60 Participants | 60 Participants | 180 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 53 / 60 | 47 / 58 | 53 / 60 |
| serious Total, serious adverse events | 16 / 60 | 13 / 58 | 14 / 60 |
Outcome results
Primary
Progression Free Survival (PFS) Time
PFS was defined as time from randomization until the first documented sign of objective radiographic disease progression (ORDP) or death from any cause. Death was considered as an event only if it was reported within 12 weeks after last tumor assessment without progression. ORDP was defined as: Bone lesion progression (2 or more new bone lesions compared to baseline) assessed with bone scintigraphy. Assessment was based on Response Evaluation Criteria in Solid Tumors version 1.0 (RECIST v1.0) modified as per Prostate Cancer Working Group 2 (PCWG-2); Soft-tissue lesion progression assessed with CT scans according to RECIST v1.0 modified as per PCWG-2; Presence of skeletal events defined as cord compression/fracture documented via a scheduled or unscheduled radiographic assessment triggered by increased pain or other signs and/or symptoms, based on the investigator's discretion; Non-radiological events, including emergency bone irradiation and surgery, were not investigated.
Time frame: Time from randomization until data cut-off date (30 April 2013), assessed up to 2 years
Population: Intention-to-treat (ITT) analysis set included all the subjects who were randomized in the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo + SoC | Progression Free Survival (PFS) Time | 3.3 months |
| EMD 525797 750 mg + SoC | Progression Free Survival (PFS) Time | 3.4 months |
| EMD 525797 1500 mg + SoC | Progression Free Survival (PFS) Time | 4.3 months |
95% CI: [0.57, 1.39]
95% CI: [0.52, 1.26]
Secondary
Bone and Soft Tissue Lesions Composite Tumor Response
Bone and soft tissue lesions composite tumor response was defined as the presence of both a confirmed CR or PR, documented by CT scans, and a DC in bone lesions, documented by bone scintigraphy. CR was defined as disappearance of all target and non-target lesions and PR was defined as at least 30% decrease in the sum of the longest diameter of target lesions and non-complete response/non-progressive disease in non-target lesions. Presence of DC in bone lesions was defined as the appearance of less than 2 new bone lesions.
Time frame: Time from randomization until data cut-off date (30 April 2013), assessed up to 2 years
Population: ITT analysis set included all the subjects who were randomized in the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + SoC | Bone and Soft Tissue Lesions Composite Tumor Response | 0 Subjects |
| EMD 525797 750 mg + SoC | Bone and Soft Tissue Lesions Composite Tumor Response | 0 Subjects |
| EMD 525797 1500 mg + SoC | Bone and Soft Tissue Lesions Composite Tumor Response | 0 Subjects |
Secondary
Minimum Percentage Change From Baseline in PSA Serum Concentration
Time frame: Baseline, up to data cut-off date (30 April 2013), assessed up to 2 years
Population: ITT analysis set included all the subjects who were randomized in the study. N signifies the total number of subjects evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo + SoC | Minimum Percentage Change From Baseline in PSA Serum Concentration | 24.00 Percent change | Standard Deviation 86.156 |
| EMD 525797 750 mg + SoC | Minimum Percentage Change From Baseline in PSA Serum Concentration | 35.65 Percent change | Standard Deviation 127.677 |
| EMD 525797 1500 mg + SoC | Minimum Percentage Change From Baseline in PSA Serum Concentration | 14.70 Percent change | Standard Deviation 50.841 |
Secondary
Minimum Percentage Change From Baseline in the Number of Circulating Tumor Cells (CTCs)
Time frame: Time from randomization until data cut-off date (30 April 2013), assessed up to 2 years
Population: ITT analysis set included all the subjects who were randomized in the study. N signifies the total number of subjects evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo + SoC | Minimum Percentage Change From Baseline in the Number of Circulating Tumor Cells (CTCs) | 49.02 Percent change | Standard Deviation 127.643 |
| EMD 525797 750 mg + SoC | Minimum Percentage Change From Baseline in the Number of Circulating Tumor Cells (CTCs) | 354.74 Percent change | Standard Deviation 1038.195 |
| EMD 525797 1500 mg + SoC | Minimum Percentage Change From Baseline in the Number of Circulating Tumor Cells (CTCs) | 280.58 Percent change | Standard Deviation 482.653 |
Secondary
Number of Subjects With Any Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, and TEAEs Leading to Discontinuation
An AE was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. A serious adverse event was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAEs were defined as those AEs that started between first dose of study drug and up to 50 days after last dose.
Time frame: From the first dose of study drug administration until 50 days after the last dose of study drug administration or until cut-off date (30 April 2013), assessed up to 2 years
Population: The Safety analysis set included all the randomized subjects who received at least 1 dose of planned trial treatment and had at least one safety assessment following the trial treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo + SoC | Number of Subjects With Any Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, and TEAEs Leading to Discontinuation | TEAEs | 55 Subjects |
| Placebo + SoC | Number of Subjects With Any Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, and TEAEs Leading to Discontinuation | Serious TEAEs | 16 Subjects |
| Placebo + SoC | Number of Subjects With Any Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, and TEAEs Leading to Discontinuation | TEAEs leading to death | 2 Subjects |
| Placebo + SoC | Number of Subjects With Any Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, and TEAEs Leading to Discontinuation | TEAEs Leading to Permanent Discontinuation | 5 Subjects |
| EMD 525797 750 mg + SoC | Number of Subjects With Any Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, and TEAEs Leading to Discontinuation | TEAEs Leading to Permanent Discontinuation | 11 Subjects |
| EMD 525797 750 mg + SoC | Number of Subjects With Any Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, and TEAEs Leading to Discontinuation | TEAEs | 49 Subjects |
| EMD 525797 750 mg + SoC | Number of Subjects With Any Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, and TEAEs Leading to Discontinuation | TEAEs leading to death | 2 Subjects |
| EMD 525797 750 mg + SoC | Number of Subjects With Any Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, and TEAEs Leading to Discontinuation | Serious TEAEs | 13 Subjects |
| EMD 525797 1500 mg + SoC | Number of Subjects With Any Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, and TEAEs Leading to Discontinuation | TEAEs Leading to Permanent Discontinuation | 8 Subjects |
| EMD 525797 1500 mg + SoC | Number of Subjects With Any Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, and TEAEs Leading to Discontinuation | Serious TEAEs | 14 Subjects |
| EMD 525797 1500 mg + SoC | Number of Subjects With Any Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, and TEAEs Leading to Discontinuation | TEAEs leading to death | 3 Subjects |
| EMD 525797 1500 mg + SoC | Number of Subjects With Any Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, and TEAEs Leading to Discontinuation | TEAEs | 53 Subjects |
Secondary
Number of Subjects With New Bone Lesions Compared to Baseline
New bone lesions were evaluated by bone scintigraphy for subjects with bone lesions at baseline.
Time frame: Time from randomization until data cut-off date (30 April 2013), assessed up to 2 years
Population: ITT analysis set included all the subjects randomized in the study. N signifies the total number of subjects evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + SoC | Number of Subjects With New Bone Lesions Compared to Baseline | 40 Subjects |
| EMD 525797 750 mg + SoC | Number of Subjects With New Bone Lesions Compared to Baseline | 34 Subjects |
| EMD 525797 1500 mg + SoC | Number of Subjects With New Bone Lesions Compared to Baseline | 34 Subjects |
Secondary
Number of Subjects With Presence of DC in Bone Lesions
Presence of DC in bone lesions was defined as the appearance of less than 2 new bone lesions, documented by bone scintigraphy.
Time frame: At Weeks 13, 19 and 25
Population: ITT analysis set included all the subjects randomized in the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo + SoC | Number of Subjects With Presence of DC in Bone Lesions | Week 19 | 2 Subjects |
| Placebo + SoC | Number of Subjects With Presence of DC in Bone Lesions | Week 13 | 4 Subjects |
| Placebo + SoC | Number of Subjects With Presence of DC in Bone Lesions | Week 25 | 2 Subjects |
| EMD 525797 750 mg + SoC | Number of Subjects With Presence of DC in Bone Lesions | Week 19 | 7 Subjects |
| EMD 525797 750 mg + SoC | Number of Subjects With Presence of DC in Bone Lesions | Week 13 | 7 Subjects |
| EMD 525797 750 mg + SoC | Number of Subjects With Presence of DC in Bone Lesions | Week 25 | 4 Subjects |
| EMD 525797 1500 mg + SoC | Number of Subjects With Presence of DC in Bone Lesions | Week 13 | 7 Subjects |
| EMD 525797 1500 mg + SoC | Number of Subjects With Presence of DC in Bone Lesions | Week 25 | 3 Subjects |
| EMD 525797 1500 mg + SoC | Number of Subjects With Presence of DC in Bone Lesions | Week 19 | 6 Subjects |
Secondary
Number of Subjects With Presence of Prostate Specific Antigen (PSA) Response
PSA response was defined as a decrease greater than 50 percent (%) in PSA value from baseline for 2 consecutive evaluations greater than or equal to (\>=) 3 Weeks apart.
Time frame: Time from randomization until data cut-off date (30 April 2013), assessed up to 2 years
Population: ITT analysis set included all the subjects who were randomized in the study. N signifies the total number of subjects evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + SoC | Number of Subjects With Presence of Prostate Specific Antigen (PSA) Response | 3 Subjects |
| EMD 525797 750 mg + SoC | Number of Subjects With Presence of Prostate Specific Antigen (PSA) Response | 6 Subjects |
| EMD 525797 1500 mg + SoC | Number of Subjects With Presence of Prostate Specific Antigen (PSA) Response | 5 Subjects |
Secondary
Number of Subjects With Presence of Skeletal Related Events
Presence of skeletal related events was defined as cord compression or fracture documented via a scheduled or unscheduled radiographic assessment triggered by increased pain or other signs and/or symptoms at the investigator discretion. Non-radiological events, including emergency bone irradiation and surgery, were not investigated.
Time frame: Time from randomization until data cut-off date (30 April 2013), assessed up to 2 years
Population: ITT analysis set included all the subjects who were randomized in the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + SoC | Number of Subjects With Presence of Skeletal Related Events | 2 Subjects |
| EMD 525797 750 mg + SoC | Number of Subjects With Presence of Skeletal Related Events | 8 Subjects |
| EMD 525797 1500 mg + SoC | Number of Subjects With Presence of Skeletal Related Events | 3 Subjects |
Secondary
Number of Subjects With Presence of Tumor Response and Disease Control (DC) in Soft Tissue Lesions
Presence of tumor response in soft tissue lesions was defined as the presence of at least 1 confirmed complete response (CR) or confirmed partial response (PR) in soft tissue lesions, documented by computed tomography (CT) scans. Presence of DC in soft tissue lesions was defined as the presence of at least 1 confirmed CR or confirmed PR or stable disease (SD) lasting at least 12 weeks after randomization. Tumor response assessments were based on RECIST v1.0 modified according to the PCWG-2. The response was evaluated for subjects with measurable disease at baseline. According to RECIST v1.0, CR=disappearance of all target and non-target lesions; PR=at least 30% decrease in the sum of the longest diameter of target lesions and non-complete response/non-progressive disease in non-target lesions.
Time frame: Time from randomization until data cut-off date (30 April 2013), assessed up to 2 years
Population: ITT analysis set included all the subjects who were randomized in the study. N signifies the total number of subjects evaluable for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo + SoC | Number of Subjects With Presence of Tumor Response and Disease Control (DC) in Soft Tissue Lesions | Tumor response | 1 Subjects |
| Placebo + SoC | Number of Subjects With Presence of Tumor Response and Disease Control (DC) in Soft Tissue Lesions | Disease control | 2 Subjects |
| EMD 525797 750 mg + SoC | Number of Subjects With Presence of Tumor Response and Disease Control (DC) in Soft Tissue Lesions | Tumor response | 0 Subjects |
| EMD 525797 750 mg + SoC | Number of Subjects With Presence of Tumor Response and Disease Control (DC) in Soft Tissue Lesions | Disease control | 3 Subjects |
| EMD 525797 1500 mg + SoC | Number of Subjects With Presence of Tumor Response and Disease Control (DC) in Soft Tissue Lesions | Tumor response | 1 Subjects |
| EMD 525797 1500 mg + SoC | Number of Subjects With Presence of Tumor Response and Disease Control (DC) in Soft Tissue Lesions | Disease control | 4 Subjects |
Secondary
Overall Minimum Percentage Change From Previous Time Point in Circulating Tumor Cells (CTC)
Time frame: Cycle 1, Day 1 (Week 1): pre-dose, Cycle 3, Day 1 (Week 7): pre-dose, and Cycle 5, Day 1 (Week 13): pre-dose
Population: ITT analysis set included all the subjects who were randomized in the study. N signifies the total number of subjects evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo + SoC | Overall Minimum Percentage Change From Previous Time Point in Circulating Tumor Cells (CTC) | 9.54 Percent change | Standard Deviation 103.225 |
| EMD 525797 750 mg + SoC | Overall Minimum Percentage Change From Previous Time Point in Circulating Tumor Cells (CTC) | 223.97 Percent change | Standard Deviation 868.941 |
| EMD 525797 1500 mg + SoC | Overall Minimum Percentage Change From Previous Time Point in Circulating Tumor Cells (CTC) | 179.11 Percent change | Standard Deviation 446.428 |
Secondary
Overall Survival
Overall Survival was defined as the time from the date of randomization to the date of death from any cause.
Time frame: Time from randomization until data cut-off date (30 April 2013), assessed up to 2 years
Population: ITT analysis set included all the subjects who were randomized in the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo + SoC | Overall Survival | NA months |
| EMD 525797 750 mg + SoC | Overall Survival | NA months |
| EMD 525797 1500 mg + SoC | Overall Survival | NA months |
95% CI: [0.52, 2.31]
95% CI: [0.47, 2.15]
Secondary
Pharmacokinetic Parameter: Clearance of Intravenously Administered EMD 525797 After First Dose (CL) and Clearance in Steady State of EMD52597 After Fifth Dose (CLss)
The apparent total body clearance of drug following intravenous administration (CL); The apparent total body clearance of drug at steady state following intravenous administration (CLss).
Time frame: Cycle 1 (Week 1) and cycle 5 (Week 13): Day 1: pre-dose, End of Infusion (EOI), 4, 8, 24, 48, 96, 168, 336, and 504 hours after start of infusion; Cycles 3 and 4 (Weeks 7 and 10), Day 1: pre-dose; Cycle 7 (Week 19), Day 1: pre-dose and EOI
Population: Pharmacokinetic Analysis Set (PKA) included all the randomized subjects who received at least the first dose of the trial drug and provided sufficient data for a concentration time profile for EMD 525797. n signifies the number of subjects evaluable for each category in the evaluated group, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo + SoC | Pharmacokinetic Parameter: Clearance of Intravenously Administered EMD 525797 After First Dose (CL) and Clearance in Steady State of EMD52597 After Fifth Dose (CLss) | First dose: CL (n=4, 6) | 0.017 Liter per hour | Standard Deviation 0.007 |
| Placebo + SoC | Pharmacokinetic Parameter: Clearance of Intravenously Administered EMD 525797 After First Dose (CL) and Clearance in Steady State of EMD52597 After Fifth Dose (CLss) | Fifth dose: CLss (n=2, 4) | 0.017 Liter per hour | Standard Deviation 0.002 |
| EMD 525797 750 mg + SoC | Pharmacokinetic Parameter: Clearance of Intravenously Administered EMD 525797 After First Dose (CL) and Clearance in Steady State of EMD52597 After Fifth Dose (CLss) | First dose: CL (n=4, 6) | 0.013 Liter per hour | Standard Deviation 0.003 |
| EMD 525797 750 mg + SoC | Pharmacokinetic Parameter: Clearance of Intravenously Administered EMD 525797 After First Dose (CL) and Clearance in Steady State of EMD52597 After Fifth Dose (CLss) | Fifth dose: CLss (n=2, 4) | 0.010 Liter per hour | Standard Deviation 0.001 |
Secondary
Pharmacokinetic Parameter: Volume of Distribution of EMD 525797 After the First Dose (V) and in Steady State After the Fifth Dose (Vss) of Intravenous Infusion
The apparent volume of distribution during the terminal phase following intravenous administration (V). The estimate of the apparent volume of distribution at steady state following intravenous administration (Vss).
Time frame: Cycle 1 (Week 1) and cycle 5 (Week 13): Day 1: pre-dose, End of Infusion (EOI), 4, 8, 24, 48, 96, 168, 336, and 504 hours after start of infusion; Cycles 3 and 4 (Weeks 7 and 10), Day 1: pre-dose; Cycle 7 (Week 19), Day 1: pre-dose and EOI
Population: PKA included all the randomized subjects who received at least the first dose of the trial drug and provided sufficient data for a concentration time profile for EMD 525797. n signifies the number of subjects evaluable for each category in the evaluated group, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo + SoC | Pharmacokinetic Parameter: Volume of Distribution of EMD 525797 After the First Dose (V) and in Steady State After the Fifth Dose (Vss) of Intravenous Infusion | First dose (n=4, 6) | 4.55 liter | Standard Deviation 1.02 |
| Placebo + SoC | Pharmacokinetic Parameter: Volume of Distribution of EMD 525797 After the First Dose (V) and in Steady State After the Fifth Dose (Vss) of Intravenous Infusion | Fifth dose (n=2, 4) | 4.81 liter | — |
| EMD 525797 750 mg + SoC | Pharmacokinetic Parameter: Volume of Distribution of EMD 525797 After the First Dose (V) and in Steady State After the Fifth Dose (Vss) of Intravenous Infusion | First dose (n=4, 6) | 4.60 liter | Standard Deviation 0.74 |
| EMD 525797 750 mg + SoC | Pharmacokinetic Parameter: Volume of Distribution of EMD 525797 After the First Dose (V) and in Steady State After the Fifth Dose (Vss) of Intravenous Infusion | Fifth dose (n=2, 4) | 5.18 liter | Standard Deviation 0.56 |
Secondary
Time to Tumor Progression
Time to tumor progression was defined as the time from the date of randomization to the date of ORDP. ORDP was defined as: Bone lesion progression (2 or more new bone lesions compared to baseline) assessed with bone scintigraphy, which had to be confirmed by bone scintigraphy 6 weeks later if subjects remained asymptomatic or mildly symptomatic. Assessments were to be based on RECIST v1.0 modified according to PCWG-2; Soft-tissue lesion progression assessed with CT scans according to RECIST v1.0 modified as per PCWG-2; Presence of skeletal events defined as cord compression or fracture documented via a scheduled or unscheduled radiographic assessment triggered by increased pain or other signs and/or symptoms, based on the investigator's discretion; Non-radiological events, including emergency bone irradiation and surgery, were not investigated.
Time frame: Time from randomization until data cut-off date (30 April 2013), assessed up to 2 years
Population: ITT analysis set included all the subjects who were randomized in the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo + SoC | Time to Tumor Progression | 3.3 months |
| EMD 525797 750 mg + SoC | Time to Tumor Progression | 3.4 months |
| EMD 525797 1500 mg + SoC | Time to Tumor Progression | 4.6 months |
95% CI: [0.58, 1.44]
95% CI: [0.52, 1.27]
Other Pre-specified
To Explore the Relationship Between Number and/or Changes of Numbers of Biomarker and the Clinical Outcome
Time frame: From the date of randomization up to data cut-off date (30 April 2013), assessed up to 2 years
Population: Data for this outcome measure was presented graphically as per planned analysis but not statistically summarized.