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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
EMD Serono
ClinicalTrials.gov Identifier:
NCT01360840
First received: April 15, 2011
Last updated: November 9, 2015
Last verified: November 2015

April 15, 2011
November 9, 2015
April 2011
April 2013   (final data collection date for primary outcome measure)
Progression Free Survival (PFS) Time [ Time Frame: Time from randomization until data cut-off date (30 April 2013), assessed up to 2 years ] [ Designated as safety issue: No ]
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.
Progression Free Survival [ Time Frame: anticipated average time frame of 2 years ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01360840 on ClinicalTrials.gov Archive Site
  • Overall Survival [ Time Frame: Time from randomization until data cut-off date (30 April 2013), assessed up to 2 years ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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).
  • Overall Survival [ Time Frame: anticipated average time frame of 2 years ] [ Designated as safety issue: No ]
  • Time to progression [ Time Frame: anticipated average time frame of 2 years ] [ Designated as safety issue: Yes ]
  • PSA response [ Time Frame: anticipated average time frame of 2 years ] [ Designated as safety issue: No ]
  • 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 EMD 525797 such as CL (L/h) and Vd (L) [ Time Frame: anticipated average time frame of 2 years ] [ Designated as safety issue: Yes ]
  • Number of treatment emergent adverse events [ Time Frame: anticipated average time frame of 2 years ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
Not Provided
 
EMD 525797 in Subjects With Asymptomatic or Mildly Symptomatic Metastatic Castrate-resistant Prostate Cancer
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).
Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Prostate Cancer Metastatic
  • 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).
  • 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)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
180
July 2014
April 2013   (final data collection date for primary outcome measure)

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
Male
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Australia,   Belgium,   Canada,   France,   Germany,   Netherlands,   Poland,   Russian Federation,   Slovakia,   South Africa,   Spain
 
NCT01360840
EMR 62242-006
Yes
Not Provided
Not Provided
EMD Serono
EMD Serono
Not Provided
Study Director: Medical Responsible EMD Serono Inc., an affiliate of Merck KGaA, Darmstadt, Germany
EMD Serono
November 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP