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

• ClinicalTrials.gov Identifier: NCT01360840
• Recruitment Status: Completed
• First Posted: May 26, 2011
• Results First Posted: December 14, 2015
• Last Update Posted: December 14, 2015
• Sponsor: EMD Serono
• Information provided by (Responsible Party): EMD Serono

Tracking Information

• First Submitted Date: April 15, 2011
• First Posted Date: May 26, 2011
• Results First Submitted Date: July 24, 2015
• Results First Posted Date: December 14, 2015
• Last Update Posted Date: December 14, 2015
• Study Start Date: April 2011
• Actual Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 9, 2015)

Progression Free Survival (PFS) Time [ Time Frame: 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.

• Original Primary Outcome Measures (submitted: May 25, 2011): Progression Free Survival [ Time Frame: anticipated average time frame of 2 years ]

Current Secondary Outcome Measures (submitted: November 9, 2015)

• Overall Survival [ Time Frame: 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.
• Time to Tumor Progression [ Time Frame: 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 Frame: 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 Frame: 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 [ Time Frame: 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 Frame: 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 Skeletal Related Events [ Time Frame: 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.
• Number of Subjects With Presence of Prostate Specific Antigen (PSA) Response [ Time Frame: 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 [ Time Frame: 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 Frame: 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) [ 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 ]
• Number of Subjects With Any Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, and TEAEs Leading to Discontinuation [ 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 ]
  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) [ 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 ]
  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 [ 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 ]
  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).

Original Secondary Outcome Measures (submitted: May 25, 2011)

• Overall survival [ Time Frame: anticipated average time frame of 2 years ]
• Time to progression [ Time Frame: anticipated average time frame of 2 years ]
• PSA response [ Time Frame: anticipated average time frame of 2 years ]
• Population pharmacokinetics data will be used to study of the sources of variability in drug concentrations among individuals which may have an impact on efficacy or safety of EMD525797 such as CL (L/h) and Vd (L) [ Time Frame: anticipated average time frame of 2 years ]
• Number of treatment emergent adverse events [ Time Frame: anticipated average time frame of 2 years ]
• To explore the relationship between number and/or changes of numbers of circulating tumor cells (CTCs) and the clinical outcome [ Time Frame: anticipated average time frame of 2 years ]

• Current Other Pre-specified Outcome Measures (submitted: November 9, 2015): 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 ]
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: EMD 525797 in Subjects With Asymptomatic or Mildly Symptomatic Metastatic Castrate-resistant Prostate Cancer
• Official Title: 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)
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Prostate Cancer Metastatic

Intervention

• 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.
• 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).

Study Arms

• Placebo Comparator: Placebo + Standard of care (SoC)
  Interventions:

  • Other: Placebo
  • Other: Standard of Care (SoC)
• Experimental: EMD 525797 750 mg + SoC
  Interventions:

  • Drug: EMD 525797
  • Other: Standard of Care (SoC)
• Experimental: EMD 525797 1500 mg + SoC
  Interventions:

  • Drug: EMD 525797
  • Other: Standard of Care (SoC)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 13, 2014): 180
• Original Estimated Enrollment (submitted: May 25, 2011): 216
• Actual Study Completion Date: July 2014
• Actual Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Belgium, Canada, France, Germany, Netherlands, Poland, Russian Federation, Slovakia, South Africa, Spain, United States

Administrative Information

• NCT Number: NCT01360840
• Other Study ID Numbers: EMR 62242-006
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: EMD Serono
• Original Responsible Party: Dr. Dr. Heinrich Lannert, MD, PhD, Medical Director, Merck KGaA
• Current Study Sponsor: EMD Serono
• Original Study Sponsor: Merck KGaA, Darmstadt, Germany
• Collaborators: Not Provided

Investigators

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

• PRS Account: EMD Serono
• Verification Date: November 2015