Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

All Drugs and Chemicals

Hormones

Prolactin Release-Inhibiting Factors

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.

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.

Placebo

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

Standard of Care (SoC)

Medical Responsible

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).

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)

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.

Overall Survival was defined as the time from the date of randomization to the date of death from any cause.

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.

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.

New bone lesions were evaluated by bone scintigraphy for subjects with bone lesions at baseline.

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 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.

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.

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.

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.

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).

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).

EMD Serono

Subjects were administered with placebo 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. All the subjects followed the SoC consisting of the continued treatment with luteinizing-hormone releasing hormone agonists (or antagonists). In order to avoid any confounding effects, bisphosphonate treatment was initiated 2 days before start of treatment with EMD 525797.

Placebo + SoC

Subjects were administered with EMD 525797 at a dose of 750 milligram (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. All the subjects followed the SoC consisting of the continued treatment with luteinizing-hormone releasing hormone agonists (or antagonists). In order to avoid any confounding effects, bisphosphonate treatment was initiated 2 days before start of treatment with EMD 525797.

EMD 525797 750 mg + SoC

Subjects were administered with EMD 525797 at a dose of 1500 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. All the subjects followed the SoC consisting of the continued treatment with luteinizing-hormone releasing hormone agonists (or antagonists). In order to avoid any confounding effects, bisphosphonate treatment was initiated 2 days before start of treatment with EMD 525797.

EMD 525797 1500 mg + SoC

Subjects were administered with placebo 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. All the subjects followed the SoC consisting of the continued treatment with luteinizing-hormone releasing hormone agonists (or antagonists). In order to avoid any confounding effects, bisphosphonate treatment was initiated 2 days before start of treatment with EMD 525797.

Subjects were 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. All the subjects followed the SoC consisting of the continued treatment with luteinizing-hormone releasing hormone agonists (or antagonists). In order to avoid any confounding effects, bisphosphonate treatment was initiated 2 days before start of treatment with EMD 525797.

Total

Age, Continuous

Sex: Female, Male

All Subjects (ALL) analysis set included subjects who signed the Informed consent document.

Merck KGaA Communication Center

Intention-to-treat (ITT) analysis set included all the subjects who were randomized in the study.

Progression Free Survival (PFS) Time

ITT analysis set included all the subjects who were randomized in the study.

Overall Survival

Time to Tumor Progression

Tumor response

Disease control

ITT analysis set included all the subjects who were randomized in the study. "N" signifies the total number of subjects evaluable for this outcome measure.

Number of Subjects With Presence of Tumor Response and Disease Control (DC) in Soft Tissue Lesions

ITT analysis set included all the subjects randomized in the study. "N" signifies the total number of subjects evaluable for this outcome measure.

Number of Subjects With New Bone Lesions Compared to Baseline

Week 13

Week 19

Week 25

ITT analysis set included all the subjects randomized in the study.

Number of Subjects With Presence of DC in Bone Lesions

Bone and Soft Tissue Lesions Composite Tumor Response

Number of Subjects With Presence of Skeletal Related Events

Number of Subjects With Presence of Prostate Specific Antigen (PSA) Response

Minimum Percentage Change From Baseline in PSA Serum Concentration

Minimum Percentage Change From Baseline in the Number of Circulating Tumor Cells (CTCs)

Overall Minimum Percentage Change From Previous Time Point in Circulating Tumor Cells (CTC)

TEAEs

Serious TEAEs

TEAEs leading to death

TEAEs Leading to Permanent Discontinuation

The Safety analysis set included all the randomized subjects who received at least 1 dose of planned trial treatment and had at least one safety assessment following the trial treatment.

Number of Subjects With Any Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, and TEAEs Leading to Discontinuation

First dose: CL (n=4, 6)

Fifth dose: CLss (n=2, 4)

Pharmacokinetic Analysis Set (PKA) included all the randomized subjects who received at least the first dose of the trial drug and provided sufficient data for a concentration time profile for EMD 525797. "n" signifies the number of subjects evaluable for each category in the evaluated group, respectively.

Pharmacokinetic Parameter: Clearance of Intravenously Administered EMD 525797 After First Dose (CL) and Clearance in Steady State of EMD52597 After Fifth Dose (CLss)

First dose (n=4, 6)

Fifth dose (n=2, 4)

PKA included all the randomized subjects who received at least the first dose of the trial drug and provided sufficient data for a concentration time profile for EMD 525797. "n" signifies the number of subjects evaluable for each category in the evaluated group, respectively.

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

Data for this outcome measure was presented graphically as per planned analysis but not statistically summarized.

To Explore the Relationship Between Number and/or Changes of Numbers of Biomarker and the Clinical Outcome

Subjects were administered with placebo 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. All the subjects followed the standard of care (SoC) consisting of the continued treatment with luteinizing-hormone releasing hormone agonists (or antagonists). In order to avoid any confounding effects, bisphosphonate treatment was initiated 2 days before start of treatment with EMD 525797.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
EMD 525797 in Subjects With Asymptomatic or Mildly Symptomatic Metastatic Castrate-resistant Prostate Cancer	NCT01360840	Prostate Cancer...	EMD 525797 EMD 525797 Placebo Standard of Car...	18 Years -	EMD Serono
EMD 525797 in Subjects With Asymptomatic or Mildly Symptomatic Metastatic Castrate-resistant Prostate Cancer	NCT01360840	Prostate Cancer...	EMD 525797 EMD 525797 Placebo Standard of Car...	18 Years -	EMD Serono
EMD 525797 in Subjects With Asymptomatic or Mildly Symptomatic Metastatic Castrate-resistant Prostate Cancer	NCT01360840	Prostate Cancer...	EMD 525797 EMD 525797 Placebo Standard of Car...	18 Years -	EMD Serono

Spots Global Cancer Trial Database for mildly symptomatic