EMD 525797 in Subjects With Asymptomatic or Mildly Symptomatic Metastatic Castrate-resistant Prostate Cancer

Phase 2

Completed

Conditions: Prostate Cancer Metastatic

Interventions: Drug: EMD 525797
Other: Placebo
Other: Standard of Care (SoC)

Registration Number: NCT01360840

Lead Sponsor: EMD Serono

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).

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 180

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 exclusion criteria could apply

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
EMD 525797 750 mg + SoC	EMD 525797	-
EMD 525797 750 mg + SoC	Standard of Care (SoC)	-
EMD 525797 1500 mg + SoC	Standard of Care (SoC)	-
EMD 525797 1500 mg + SoC	EMD 525797	-
Placebo + Standard of care (SoC)	Placebo	-
Placebo + Standard of care (SoC)	Standard of Care (SoC)	-

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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 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.
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).
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 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 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.
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.
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.
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
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 PSA Serum Concentration	Baseline, up to data cut-off date (30 April 2013), assessed up to 2 years
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).

Trial Locations

Locations (18): Hôpitaux Civils de Colmar-CH Louis Pasteur
🇫🇷
Colmar, France
Institute Gustave Roussy
🇫🇷
Villejuif, France
Budzhet Clinical Oncology Center
🇷🇺
Izhevsk, Russian Federation
City Hospital # 2
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Petersburg, Russian Federation
Studienpraxis Urologie
🇩🇪
Reutlingen, Germany
Research Site
🇪🇸
Sabadell, Barcelone, Spain
Krasnoyarsk State Medical University Oncology and Radiotherapy Territorial Dispensary
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Krasnoyarsk, Russian Federation
Universitätsmedizin Charité, Campus Benjamin Franklin, Urologische Klinik and Poliklinik
🇩🇪
Berlin, Germany
State Institution of Healthcare Ivanovo Regional Oncology Dispensary
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Ivanovo, Russian Federation
Universitätsklinikum Tübinger, Klinik und Poliklinik für Urologie
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Tübingen, Germany
ZNA Middelheim Oncologie
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Antwerp, Belgium
Brandord Urology Research
🇨🇦
Brantford, Ontario, Canada
Exdeo Clinical Research Inc.
🇨🇦
Abbotsford, Canada
Can-Med Clinical Research Inc.
🇨🇦
Province of British Columbia, Canada
Sunnybrook Health Sciences Centre
🇨🇦
Toronto, Canada
Center Alexis Vaurrin
🇫🇷
Bourgogne, France
Universitätsklinikum Carl Gustav Carus an der Techischen Universität Dresden, Klinik und Poliklinik für Urologie
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Dresden, Germany
Altay Regional Oncology Dispensary
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Barnaul, Russian Federation