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

Prostate Cancer Metastatic Clinical Trial

— PERSEUS  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01360840
• Other study ID #: EMR 62242-006
• Status: Completed
• Phase: Phase 2
• First received: April 15, 2011
• Last updated: November 9, 2015
• Start date: April 2011
• Est. completion date: July 2014

Study information

• Verified date: November 2015
• Source: EMD Serono
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicinal Products and Health ProductsBelgium: All Ethics Committees involved (1 per site)Germany: Ethics CommissionGermany: Paul-Ehrlich-InstitutPoland: Lead Ethics CommitteePoland: 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 CommitteeFrance: 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 applicableFrance : Comité de Protection des Personnes (CPP) = Consultative Ethical CommitteeFrance : Commission Nationale de l'Ordre des Médecins (CNOM) = French Board of Pysicians.France : Hospital Internal Review Board if applicableRussia: Ministry of Health and Social Development of Russian FederationRussia: Ethics Council of The Ministry of Health and Social Development of Russian FederationRussia: Scientific Center on Expertise of Medical Application Products of The Ministry of Health and Social Development of Russian FederationNetherlands: The Central Committee on Research Involving Human Subjects (CCMO)Netherlands: Medical Ethics Review Committee (METC)Netherlands: Local Ethics Committee (1 per site)Canada: Ethics CommitteesCanada: Health CanadaUnited States: Food and Drug AdministrationUnited States: Institutional Review BoardSpain: Ministry of HealthSpain: Ministry of Health and ConsumptionSlovakia: State Institute for Drug ControlAustralia: Department of Health and Ageing Therapeutic Goods AdministrationAustralia: Human Research Ethics CommitteeAustralia: National Health and Medical Research CouncilSouth Africa: Department of HealthSouth Africa: Human Research Ethics CommitteeSouth Africa: Medicines Control CouncilSouth Africa: National Health Research Ethics Council
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 180
• Est. completion date: July 2014
• Est. primary completion date: April 2013
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

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

Related Conditions & MeSH terms

• Prostate Cancer Metastatic
• Prostatic Neoplasms

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.
• 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.
• Standard of Care (SoC)
All the subjects followed the SoC consisting of the continued treatment with luteinizing-hormone releasing hormone agonists (or antagonists).

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
EMD Serono

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  France,  Germany,  Netherlands,  Poland,  Russian Federation,  Slovakia,  South Africa,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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	No
Primary	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	No
Secondary	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	No
Secondary	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	Yes
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Minimum Percentage Change From Baseline in PSA Serum Concentration		Baseline, up to data cut-off date (30 April 2013), assessed up to 2 years	No
Secondary	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	No
Secondary	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	No
Secondary	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	Yes
Secondary	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	No
Secondary	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	No