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

EMD Serono180 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

180

Conditions

Prostate Cancer Metastatic

Interventions

EMD 525797DRUG

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 525797DRUG

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.

PlaceboOTHER

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.

Eligibility

Sex: MALEMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (71)

Outcomes

Primary Outcomes

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 frame: Time from randomization until data cut-off date (30 April 2013), assessed up to 2 years

Secondary Outcomes

Overall Survival

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

Time frame: Time from randomization until data cut-off date (30 April 2013), assessed up to 2 years

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.

Data from ClinicalTrials.gov

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Standard of Care (SoC)OTHER

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

Research Site

Pleasant Hill, California, United States

Research Site

Chicago, Illinois, United States

Research Site

New Orleans, Louisiana, United States

Research Site

Ann Arbor, Michigan, United States

Research Site

Detroit, Michigan, United States

Research Site

New Brunswick, New Jersey, United States

Research Site

Cleveland, Ohio, United States

Research Site

Dallas, Texas, United States

Research Site

Houston, Texas, United States

Research Site

Tyler, Texas, United States

...and 61 more locations

Time frame: Time from randomization until data cut-off date (30 April 2013), assessed up to 2 years

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 frame: Time from randomization until data cut-off date (30 April 2013), assessed up to 2 years

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 frame: Time from randomization until data cut-off date (30 April 2013), assessed up to 2 years

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.

Time frame: At Weeks 13, 19 and 25

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 frame: Time from randomization until data cut-off date (30 April 2013), assessed up to 2 years

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 frame: Time from randomization until data cut-off date (30 April 2013), assessed up to 2 years

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 frame: Time from randomization until data cut-off date (30 April 2013), assessed up to 2 years

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

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.

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

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).

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

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).