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

A Randomized, Double-blind, Placebo-controlled, Multicenter Phase II Trial Investigating Two Doses of EMD 525797 in Subjects With Asymptomatic or Mildly Symptomatic Metastatic Castrate-resistant Prostate Cancer (mCRPC)

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).

Study Overview

• Status: Completed
• Conditions: Prostate Cancer Metastatic
• Intervention / Treatment: Other: Placebo; Other: Standard of Care (SoC); Drug: EMD 525797; Drug: EMD 525797

• Study Type: Interventional
• Enrollment (Actual): 180
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Bendigo, Australia
    • Research Site
  • Coffs Harbour, Australia
    • Research Site
  • Darlinghurst, Australia
    • Research Site
  • Frankston, Australia
    • Research Site
  • Gosford, Australia
    • Research Site
  • Kurralta Park, Australia
    • Research Site
  • Northmead, Australia
    • Research Site
  • Port Macquarie, Australia
    • Research Site
  • Randwick, Australia
    • Research Site
  • Turnhout, Australia
    • Research Site
• Belgium
  • Antwerp, Belgium
    • ZNA Middelheim Oncologie
• Canada
  • Abbotsford, Canada
    • Exdeo Clinical Research Inc.
  • Province of British Columbia, Canada
    • Can-Med Clinical Research Inc.
  • Toronto, Canada
    • Sunnybrook Health Sciences Centre
  • Victoria, Canada
    • Research Site
  • Windsor, Canada
    • Research Site
  • Ontario
    • Brantford, Ontario, Canada
      • Brandord Urology Research
• France
  • Angers, France
    • Research Site
  • Bourgogne, France
    • Center Alexis Vaurrin
  • Caen Cedex 05, France
    • Research Site
  • Colmar, France
    • Hôpitaux Civils de Colmar-CH Louis Pasteur
  • Paris, France
    • Research Site
  • Reims, France
    • Research Site
  • Villejuif, France
    • Institute Gustave Roussy
• Germany
  • Aachen, Germany
    • Research Site
  • Berlin, Germany
    • Universitätsmedizin Charité, Campus Benjamin Franklin, Urologische Klinik and Poliklinik
  • Darmstadt, Germany
    • Research Site
  • Dresden, Germany
    • Universitätsklinikum Carl Gustav Carus an der Techischen Universität Dresden, Klinik und Poliklinik für Urologie
  • Esslingen, Germany
    • Research Site
  • Freiburg, Germany
    • Research Site
  • Hannover, Germany
    • Research Site
  • Nürtingen, Germany
    • Research Site
  • Reutlingen, Germany
    • Studienpraxis Urologie
  • Tübingen, Germany
    • Universitätsklinikum Tübinger, Klinik und Poliklinik für Urologie
• Netherlands
  • Blaricum, Netherlands
    • Research Site
  • Groningen, Netherlands
    • Research Site
  • Haarlem, Netherlands
    • Research Site
• Poland
  • Gdańsk, Poland
    • Research Site
  • Lublin, Poland
    • Research Site
  • Łódź, Poland
    • Research Site
• Russian Federation
  • Barnaul, Russian Federation
    • Research Site
  • Barnaul, Russian Federation
    • Altay Regional Oncology Dispensary
  • Ekaterinburg, Russian Federation
    • Research Site
  • Ivanovo, Russian Federation
    • State Institution of Healthcare Ivanovo Regional Oncology Dispensary
  • Izhevsk, Russian Federation
    • Budzhet Clinical Oncology Center
  • Kazan, Russian Federation
    • Research Site
  • Krasnoyarsk, Russian Federation
    • Krasnoyarsk State Medical University Oncology and Radiotherapy Territorial Dispensary
  • Omsk, Russian Federation
    • Research Site
  • Petersburg, Russian Federation
    • City Hospital # 2
  • Stavropol, Russian Federation
    • Research Site
• Slovakia
  • Presov, Slovakia
    • Research Site
• South Africa
  • Gauteng, South Africa
    • Research Site
  • Kwa-Zulu Natal, South Africa
    • Research Site
  • Pretoria Gauteng, South Africa
    • Research Site
  • Western Cape, South Africa
    • Research Site
• Spain
  • Barcelone, Spain
    • Research Site
  • Madrid, Spain
    • Research Site
  • Pamplona, Spain
    • Research Site
  • Sabadell, Barcelone, Spain
    • Research Site
• United States
  • California
    • Pleasant Hill, California, United States
      • Research Site
  • Illinois
    • Chicago, Illinois, United States
      • Research Site
  • Louisiana
    • New Orleans, Louisiana, United States
      • Research Site
  • Michigan
    • Ann Arbor, Michigan, United States
      • Research Site
    • Detroit, Michigan, United States
      • Research Site
  • New Jersey
    • New Brunswick, New Jersey, United States
      • Research Site
  • Ohio
    • Cleveland, Ohio, United States
      • Research Site
  • Texas
    • Dallas, Texas, United States
      • Research Site
    • Houston, Texas, United States
      • Research Site
    • Tyler, Texas, United States
      • Research Site
  • Virginia
    • Roanoke, Virginia, United States
      • Research Site
  • Washington
    • Spokane, Washington, United States
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo + Standard of care (SoC)	Other: Placebo; 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.; Other: Standard of Care (SoC); All the subjects followed the SoC consisting of the continued treatment with luteinizing-hormone releasing hormone agonists (or antagonists).
Experimental: EMD 525797 750 mg + SoC	Other: Standard of Care (SoC); All the subjects followed the SoC consisting of the continued treatment with luteinizing-hormone releasing hormone agonists (or antagonists).; Drug: EMD 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.; Drug: EMD 525797; Subjects will be 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.
Experimental: EMD 525797 1500 mg + SoC	Other: Standard of Care (SoC); All the subjects followed the SoC consisting of the continued treatment with luteinizing-hormone releasing hormone agonists (or antagonists).; Drug: EMD 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.; Drug: EMD 525797; Subjects will be 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 from randomization until data cut-off date (30 April 2013), assessed up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Overall Survival was defined as the time from the date of randomization to the date of death from any cause.	Time from randomization until data cut-off date (30 April 2013), assessed up to 2 years
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 from randomization until data cut-off date (30 April 2013), assessed up to 2 years
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 from randomization until data cut-off date (30 April 2013), assessed up to 2 years
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 from randomization until data cut-off date (30 April 2013), assessed up to 2 years
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.	At Weeks 13, 19 and 25
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 from randomization until data cut-off date (30 April 2013), assessed up to 2 years
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 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	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 from randomization until data cut-off date (30 April 2013), assessed up to 2 years
Minimum Percentage Change From Baseline in PSA Serum Concentration		Baseline, up to data cut-off date (30 April 2013), assessed up to 2 years
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	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.	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
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).	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
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).	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

Other Outcome Measures

Outcome 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

Collaborators and Investigators

• Sponsor: EMD Serono
• Investigators: Study Director: Medical Responsible, EMD Serono Inc., an affiliate of Merck KGaA, Darmstadt, Germany

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (Actual): April 1, 2013
• Study Completion (Actual): July 1, 2014

Study Registration Dates

• First Submitted: April 15, 2011
• First Submitted That Met QC Criteria: May 25, 2011
• First Posted (Estimate): May 26, 2011

Study Record Updates

• Last Update Posted (Estimate): December 14, 2015
• Last Update Submitted That Met QC Criteria: November 9, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Keywords: mCRPC; Asymptomatic; mildly symptomatic; metastatic castrate-resistant prostate cancer
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms
• Other Study ID Numbers: EMR 62242-006