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
  Purpose
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).

Condition Intervention Phase
Prostate Cancer Metastatic
Drug: EMD 525797
Other: Placebo
Other: Standard of Care (SoC)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by EMD Serono:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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).


Other Outcome Measures:
  • 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 ]

Enrollment: 180
Study Start Date: April 2011
Study Completion Date: July 2014
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 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: 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 1500 mg + SoC 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.
Other: Standard of Care (SoC)
All the subjects followed the SoC consisting of the continued treatment with luteinizing-hormone releasing hormone agonists (or antagonists).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01360840

  Show 71 Study Locations
Sponsors and Collaborators
EMD Serono
Investigators
Study Director: Medical Responsible EMD Serono Inc., an affiliate of Merck KGaA, Darmstadt, Germany
  More Information

No publications provided

Responsible Party: EMD Serono
ClinicalTrials.gov Identifier: NCT01360840     History of Changes
Other Study ID Numbers: EMR 62242-006 
Study First Received: April 15, 2011
Results First Received: July 24, 2015
Last Updated: November 9, 2015
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
Belgium: All Ethics Committees involved (1 per site)
Germany: Ethics Commission
Germany: Paul-Ehrlich-Institut
Poland: Lead Ethics Committee
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products - this organization act as reviewer in the name of Ministry of Health.
France: Institutional Ethical Committee
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
France : Commission Nationale d'Informatique et des Libertés (CNIL) = French Data Protection Authority if applicable
France : Comité de Protection des Personnes (CPP) = Consultative Ethical Committee
France : Commission Nationale de l'Ordre des Médecins (CNOM) = French Board of Pysicians.
France : Hospital Internal Review Board if applicable
Russia: Ministry of Health and Social Development of Russian Federation
Russia: Ethics Council of The Ministry of Health and Social Development of Russian Federation
Russia: Scientific Center on Expertise of Medical Application Products of The Ministry of Health and Social Development of Russian Federation
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Netherlands: Medical Ethics Review Committee (METC)
Netherlands: Local Ethics Committee (1 per site)
Canada: Ethics Committees
Canada: Health Canada
United States: Food and Drug Administration
United States: Institutional Review Board
Spain: Ministry of Health
Spain: Ministry of Health and Consumption
Slovakia: State Institute for Drug Control
Australia: Department of Health and Ageing Therapeutic Goods Administration
Australia: Human Research Ethics Committee
Australia: National Health and Medical Research Council
South Africa: Department of Health
South Africa: Human Research Ethics Committee
South Africa: Medicines Control Council
South Africa: National Health Research Ethics Council

Keywords provided by EMD Serono:
Asymptomatic
mildly symptomatic
metastatic castrate-resistant prostate cancer
mCRPC

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Diseases, Male
Genital Neoplasms, Male
Neoplasms
Neoplasms by Site
Prostatic Diseases
Urogenital Neoplasms

ClinicalTrials.gov processed this record on February 09, 2016