Solid TumorPhase 1NCT01327313

A Study of EMD525797 in Solid Tumor Patients in Japan

A Phase 1 study testing EMD525797 in people with Solid Tumor, run by Merck KGaA, Darmstadt, Germany at 1 site in Japan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

The primary objectives are to assess the safety and tolerability of single and repeated doses of EMD525797, and characterize Pharmacokinetics (PK). The secondary objectives are to investigate the immunogenicity and Progressive disease (PD), and to assess the anti-tumor activity of EMD525797. Read more about this study

Who is it for?: Ages 20 years and older
Conditions the study is for: Solid Tumor
What is being tested?: EMD525797
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 27 participants
Where: 1 siteJapan
Study dates: Jan 2011to Oct 2012
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 20 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Age greater than or equal to (>=) 20 years
Histologically or cytologically proven advanced or metastatic solid tumor
Evidence of progressive disease after standard chemotherapy or no standard chemotherapy
Confirmation of availability of formalin-fixed paraffin-embedded (FFPE) tumor block(s) or tissue sections
Presence of at least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.0 complete tumor assessment to be performed within the 30 days prior to the first EMD525797 administration
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1

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Estimated life expectancy of at least 3 months
Absolute Neutrophil Count (ANC) >= 1.5 x 10^9 per liter (/Liter)
Platelets >= 100 x 10^9/Liter
Haemoglobin >= 9.0 gram per deciliter (g/dL) (without transfusions)
Total bilirubin less than or equal to (<=) 1.5 x upper limit of normal (ULN)
Aspartate transaminase (AST), alanine transaminase (ALT) less than or equal to (<=) 3 x ULN
In subjects with hepatic metastasis, total bilirubin <= 3 x ULN, AST and ALT <= 5 x ULN
Prothrombin time (PT), prothrombin time/international normalized ratio (PT/INR), and activated partial thromboplastin time (APTT) within normal limits
Creatinine clearance >= 50 milliliter per minute (mL/min)
Other protocol defined inclusion criteria could also apply

Who cannot join

Previous treatment with anti-integrin therapy
Radiotherapy to bone lesions, systemic surgery, orthopedic surgery (all within the 4 week prior to treatment with EMD525797), clinically significant unhealed wound, or unrecovered bone fracture
Chronic doses of oral steroids, defined as >= 10 milligram of prednisone equivalents per day
Confirmed or clinically suspected brain or leptomeningeal metastases
Known hypersensitivity to EMD525797 or its excipients
History of allergic reactions to other monoclonal antibody therapy

Show all 20Show fewer

Antibody treatment within the past 8 weeks or chemotherapy within the 4 weeks prior to treatment with EMD525797
Uncontrolled diabetes
Uncontrolled hypertension defined as systolic blood pressure >= 160 millimeter of mercury (mmHg) and/or diastolic blood pressure >= 100 millimeter of mercury (mmHg) under resting conditions
Autoimmune diseases
Current history of chronic daily acetylsalicylic acid (ASS) therapy (ASS at doses <=100 mg is permitted)
Bleeding disorders;
History of thromboembolic events (history of superficial thrombophlebitis is not an exclusion
Anticoagulants within the past 10 days prior to the first treatment and during treatment period
Severe peripheral vascular disease or ulceration
Unstable angina pectoris, or myocardial infarction or other severe heart diseases within the past 6 months before treatment with EMD 525797
Clinical significant abnormal ECG at screening
Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent
Known HIV infection, active or chronic carrier of hepatitis B virus (HBV antigen positive or HBV DNA positive) or hepatitis C virus (HCV antibody positive)
Other protocol defined exclusion criteria could also apply

Trial locations and contacts

1 site in 1 country.

Japan1 site

For Recruiting
Locations in

Other trials in Japan

About this study

Official title: A Phase I, Open-label Trial to Investigate the Safety, Tolerability, and Pharmacokinetics of EMD525797 After Single Dose and Repeated Dosing at Different Dose Levels in Japanese Patients With Advanced or Metastatic Solid Tumors and Progressive Diseases Following Prior Chemotherapy

Conditions: Solid Tumor
Being tested: EMD525797
Keywords: alpha v integrin, antibody, solid tumor, Japanese, EMD525797

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

EMD525797Biological
Subjects will receive 250 milligram (mg) of EMD525797 intravenously every 2 weeks, until progressive disease (PD), unacceptable toxicity or withdrawal of consent.
EMD525797Biological
Subjects will receive 500 mg of EMD525797 intravenously every 2 weeks, until PD or unacceptable toxicity or withdrawal of consent.
EMD525797Biological
Subjects will receive 1000 mg of EMD525797 intravenously every 2 weeks, until PD or unacceptable toxicity or withdrawal of consent.
EMD525797Biological
Subjects will receive 1500 mg of EMD525797 intravenously every 2 weeks, until PD or unacceptable toxicity, or withdrawal of consent.

Study groups in NCT01327313
Study group	Role	What they receive
EMD525797 250 milligram (mg)	Experimental	Not described Receives: Biological: EMD525797
EMD525797 500 mg	Experimental	Not described Receives: Biological: EMD525797
EMD525797 1000 mg	Experimental	Not described Receives: Biological: EMD525797
EMD525797 1500 mg	Experimental	Not described Receives: Biological: EMD525797

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Subjects With Dose-limiting Toxicities (DLTs)
DLT was defined as any Grade 3 or 4 haematological or non-haematological toxicity occurring at any dose level until the end of Week 4, and suspected to be reasonably related to the investigational medicinal product by the Investigator and/or Sponsor. Toxicities not considered to be DLTs are as follows- Allergic reactions or anaphylaxis; any Grade 3 or 4 out-of-range laboratory values without any clinical correlate, which were reversible within 7 days, unless the Investigator decided this event is clinically significant. For this reason Grade 3 or 4 out-of-range laboratory values must be re-assessed within 7 days. In case the Investigator provides the subject any treatment(s) due to the out-of-range laboratory values, the event was regarded as a DLT.
Measured: Baseline up to Week 4
Maximum Observed Serum Concentration (Cmax): After Single Dose
Measured: Pre-dose, hour 1(end of infusion [EOI]), 4, 8, 24, 48, and 96 hours after start of infusion at Week 1
Maximum Observed Serum Concentration (Cmax) of EMD 525797:After Multiple Dose
Measured: Pre-dose, hour 1 (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 5
Area Under the Curve From Time Zero to Last Quantifiable Concentration(AUC0-t) of EMD 525797: After Single Dose
Area under the serum concentration-time curve from time zero to the last sampling time at which the concentration is at or above Lower limit of quantification (LLQ).
Measured: Pre-dose, hour 1 (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 1
Area Under the Curve From Time Zero to Last Quantifiable Concentration(AUC0-t) of EMD 525797: After Multiple Dose
Area under the serum concentration-time curve from time zero to the last sampling time at which the concentration is at or above LLQ.
Measured: Pre-dose, hour 1 (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 5
Total Body Clearance (CL) of EMD 525797: After Single Dose
Total body clearance of drug in serum was calculated: as CL= Dose divided by Area under the serum concentration-time curve from time zero to infinity (AUC0-inf).
Measured: Pre-dose, hour 1 (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 1
Total Body Clearance at Steady State (CLss) of EMD 525797
Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. CL of drug in serum was calculated as : CL= Dose/ AUC0-inf. Area under the serum concentration-time curve from time zero to infinity (AUC0-inf), calculated as AUC0-t + AUCextra. AUCextra represents an extrapolated value obtained by Clast / λz, where Clast is the calculated serum concentration at the last sampling time point at which the measured serum concentration is at or above LLQ and λz is the elimination rate constant.
Measured: Pre-dose, hour 1 (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 5
Apparent Volume of Distribution (Vz): After Single Dose
Apparent volume of distribution during the terminal phase, calculated as Vz = Dose/AUC0-inf multiplied by elimination rate constant [λz]) following single dose. Area under the serum concentration-time curve from time zero to infinity, calculated (AUC0-inf) as AUC0-t + AUCextra. AUCextra represents an extrapolated value obtained by Clast / λz, where Clast is the calculated serum concentration at the last sampling time point at which the measured serum concentration is at or above LLQ and λz is the elimination rate constant. And the elimination rate constant obtained from linear regression of the terminal phase of the log transformed concentration-time data. A minimum of three points is required to calculate λz.
Measured: Pre-dose, hour 1 (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 1
Pharmacokinetics of EMD 525797 - Trough Values
The observed serum concentration immediately before next dosing determined directly from the serum concentration-time profile of each subject (= trough concentration).
Measured: Pre-dose, hour 1 (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 5
Apparent Volume of Distribution: After Multiple Dose
Apparent volume of distribution during the terminal phase, calculated as Vz = Dose/(Area under the serum concentration-time curve within one complete dosing interval [AUCtau]* λz) following multiple dose.
Measured: Pre-dose, hour 1 (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 5

Secondary outcomes (19)

Number of Subjects With Overall Tumor Response
Overall tumor response was defined as the presence of at least one confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.0. Complete response was defined as the disappearance of all target and non-target lesions and normalization of serum levels of tumor markers. PR is at least a 30 percent (%) decrease in the sum of the longest diameter (LD) of target lesions, taking as a reference the baseline sum LD.
Measured: Baseline up to Week 36
Number of Subjects With Clinical Benefit
Clinical benefit was defined as presence of at least one confirmed CR, PR, or stable disease (SD) lasting at least 12 weeks according to RECIST v1.0. Per RECIST v1.0: CR was defined as disappearance of all target and non-target lesions and normalization of serum levels of tumor markers . PR was defined as >=30% decrease in sum of longest diameters of target lesions taking as reference baseline sum longest diameters associated to non-progressive disease response for non-target lesions. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease taking as reference smallest sum of longest dimensions since treatment started associated to non-progressive disease response for non-target lesions.
Measured: Baseline up to Week 36
Progression-free Survival (PFS)
PFS time was defined as the time (in months) from the first dosing date to the date of first documentation of disease progression as reported and documented by the Investigator (i.e. radiological progression per RECIST version 1.0) or death for any cause within 12 weeks after last tumor assessment. Subjects without event are censored on the date of last tumor assessment.
Measured: From first dosing date until disease progression or death, maximum up to Week 36
Apparent Terminal Half Life (t1/2): After Single Dose
Measured: Pre-dose, end of infusion (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 1
Apparent Terminal Half Life (t1/2): After Multiple Dose
Measured: Pre-dose, EOI, 4, 8, 24, 48, and 96 hours after start of infusion at Week 5
Time to Maximum Observed Serum Concentration (Tmax): After Single Dose
Measured: Pre-dose, end of infusion (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 1
Time to Maximum Observed Serum Concentration (Tmax): After Multiple Dose
Measured: Pre-dose, EOI, 4, 8, 24, 48, and 96 hours after start of infusion at Week 5
Elimination Rate Constant (λz): After Single Dose
The elimination rate constant obtained from linear regression of the terminal phase of the log transformed concentration-time data.
Measured: Pre-dose, end of infusion (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 1
Elimination Rate Constant ( λ z): After Multiple Dose
The elimination rate constant obtained from linear regression of the terminal phase of the log transformed concentration-time data.
Measured: Pre-dose, EOI, 4, 8, 24, 48, and 96 hours after start of infusion at Week 5
Minimum Observed Serum Concentration (Cmin) After Multiple Doses
The observed minimum serum concentration determined directly from the serum concentration-time profile of each subject.
Measured: Pre-dose, EOI, 4, 8, 24, 48, and 96 hours after start of infusion at Week 5
Observed Serum Concentration Immediately Before Next Dosing (Cpre)
The observed serum concentration immediately before next dosing determined directly from the serum concentration-time profile of each subject (= trough concentration)
Measured: Pre-dose, EOI, 4, 8, 24, 48, and 96 hours after start of infusion at Week 5
Average Serum Concentration at Steady State (Cav)
The Cav was calculated by dividing the area under the serum concentration-time curve within one complete dosing interval (AUCtau) by the dosing interval (2 weeks or 336 hoursi.e. Cav =AUCtau/tau).
Measured: Pre-dose, EOI, 4, 8, 24, 48, and 96 hours after start of infusion at Week 5
Area Under the Serum Concentration-time Curve Within One Complete Dosing Interval( AUCtau): After Single Dose
Measured: Pre-dose, end of infusion (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 1
Area Under the Serum Concentration-time Curve Within One Complete Dosing Interval( AUCtau): After Multiple Dose
Measured: Pre-dose, EOI, 4, 8, 24, 48, and 96 hours after start of infusion at Week 5
Volume of Distribution at Steady State (Vss)
Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) was the apparent volume of distribution at steady-state.
Measured: Pre-dose, EOI, 4, 8, 24, 48, and 96 hours after start of infusion at Week 5
Mean Residency Time (MRT0-inf)
MRT0-inf of drug in the body was calculated by dividing the area under the first moment curve from time zero to infinity with area under the first moment curve from time zero to infinity minus half of infusion of duration (MRT0-inf = AUMC0-inf/AUMC0-inf - T/2).
Measured: Pre-dose, end of infusion (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 1
Mean Residence Time at Steady State (MRTss)
MRTss = (AUMCtau + tau(AUCinf - AUCtau))/ AUCtau) - T/2, where AUMCtau was the area under the first moment curve within one complete dosing interval and T was the infusion duration. Area under the serum concentration-time curve from time zero to infinity, calculated as AUC0-t + AUCextra. AUCextra represents an extrapolated value obtained by Clast / λz, where Clast is the calculated serum concentration at the last sampling time point at which the measured serum concentration is at or above LLQ and λz is the elimination rate constant.
Measured: Pre-dose, EOI, 4, 8, 24, 48, and 96 hours after start of infusion at Week 5
Percentage Peak-Trough Fluctuation (PTF)
The peak trough fluctuation over one dosing interval at steady state, calculated as PTF (%) = ( [Cmax - Cmin] / Cav ) multiplied by 100.
Measured: Pre-dose, EOI, 4, 8, 24, 48, and 96 hours after start of infusion at Week 5
Accumulation Ratio (Rac)
Accumulation ratio for AUC, calculated as area under the serum concentration-time curve within one complete dosing interval at 3rd infusion divided by area under the serum concentration-time curve within one complete dosing interval at 1st infusion.
Measured: Pre-dose, end of infusion (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 1 and Week 5

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jan 2011Oct 2012

First posted1 Apr 2011 (estimated)
Study startJan 2011
Primary completionJul 2012
Study completionOct 2012

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Solid TumorStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 27 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01327313
Sponsor's protocol ID: EMR200017-007
Status last verified: Apr 2016
First submitted: 30 Mar 2011
Last updated: 13 May 2016
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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A Safety and Efficacy Extension Study of Pertuzumab in Patients With Solid Tumors Previously Enrolled in a Hoffmann-La Roche-Sponsored Pertuzumab Clinical Trial
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IL-12 Genetically Engineered Myeloid Cells in Participants With Relapsed, Refractory Solid Tumors
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All Solid Tumor trials

Study at a glance

From the registry record, last updated by the sponsor on 13 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase I, Open-label Trial to Investigate the Safety, Tolerability, and Pharmacokinetics of EMD525797 After Single Dose and Repeated Dosing at Different Dose Levels in Japanese Patients With Advanced or Metastatic Solid Tumors and Progressive Diseases Following Prior Chemotherapy
ClinicalTrials.gov ID: NCT01327313
Acronym / sponsor ID: EMR200017-007
Conditions: Solid Tumor
Keywords: alpha v integrin, antibody, solid tumor, Japanese, EMD525797
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 27 participants (actual)
Lead sponsor: Merck KGaA, Darmstadt, GermanyIndustry (pharma, biotech, devices)
Study start: Jan 2011
Primary completion: Jul 2012 (actual)
Study completion: Oct 2012 (actual)
First posted: 1 Apr 2011 (estimated)
Results: Posted 13 May 2016

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 4

Arm	Type	Receives
EMD525797 250 milligram (mg)	Experimental	Biological: EMD525797
EMD525797 500 mg	Experimental	Biological: EMD525797
EMD525797 1000 mg	Experimental	Biological: EMD525797
EMD525797 1500 mg	Experimental	Biological: EMD525797

Who may qualify

Ages: 20 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (16 listed)

Age greater than or equal to (>=) 20 years
Histologically or cytologically proven advanced or metastatic solid tumor
Evidence of progressive disease after standard chemotherapy or no standard chemotherapy
Confirmation of availability of formalin-fixed paraffin-embedded (FFPE) tumor block(s) or tissue sections
Presence of at least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.0 complete tumor assessment to be performed within the 30 days prior to the first EMD525797 administration

Key exclusion criteria (20 listed)

Previous treatment with anti-integrin therapy
Radiotherapy to bone lesions, systemic surgery, orthopedic surgery (all within the 4 week prior to treatment with EMD525797), clinically significant unhealed wound, or unrecovered bone fracture
Chronic doses of oral steroids, defined as >= 10 milligram of prednisone equivalents per day
Confirmed or clinically suspected brain or leptomeningeal metastases
Known hypersensitivity to EMD525797 or its excipients

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
EMD525797Subjects will receive 250 milligram (mg) of EMD525797 intravenously every 2 weeks, until progressive disease (PD), unacceptable toxicity or withdrawal of consent.	Biological	EMD525797 250 milligram (mg)
EMD525797Subjects will receive 500 mg of EMD525797 intravenously every 2 weeks, until PD or unacceptable toxicity or withdrawal of consent.	Biological	EMD525797 500 mg
EMD525797Subjects will receive 1000 mg of EMD525797 intravenously every 2 weeks, until PD or unacceptable toxicity or withdrawal of consent.	Biological	EMD525797 1000 mg
EMD525797Subjects will receive 1500 mg of EMD525797 intravenously every 2 weeks, until PD or unacceptable toxicity, or withdrawal of consent.	Biological	EMD525797 1500 mg

Primary outcome

Number of Subjects With Dose-limiting Toxicities (DLTs)
Time frame: Baseline up to Week 4
DLT was defined as any Grade 3 or 4 haematological or non-haematological toxicity occurring at any dose level until the end of Week 4, and suspected to be reasonably related to the investigational medicinal product by the Investigator and/or Sponsor. Toxicities not considered to be DLTs are as follows- Allergic reactions or anaphylaxis; any Grade 3 or 4 out-of-range laboratory values without any clinical correlate, which were reversible within 7 days, unless the Investigator decided this event is clinically significant. For this reason Grade 3 or 4 out-of-range laboratory values must be re-assessed within 7 days. In case the Investigator provides the subject any treatment(s) due to the out-of-range laboratory values, the event was regarded as a DLT.
Maximum Observed Serum Concentration (Cmax): After Single Dose
Time frame: Pre-dose, hour 1(end of infusion [EOI]), 4, 8, 24, 48, and 96 hours after start of infusion at Week 1
Maximum Observed Serum Concentration (Cmax) of EMD 525797:After Multiple Dose
Time frame: Pre-dose, hour 1 (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 5
Area Under the Curve From Time Zero to Last Quantifiable Concentration(AUC0-t) of EMD 525797: After Single Dose
Time frame: Pre-dose, hour 1 (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 1
Area under the serum concentration-time curve from time zero to the last sampling time at which the concentration is at or above Lower limit of quantification (LLQ).
Area Under the Curve From Time Zero to Last Quantifiable Concentration(AUC0-t) of EMD 525797: After Multiple Dose
Time frame: Pre-dose, hour 1 (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 5
Area under the serum concentration-time curve from time zero to the last sampling time at which the concentration is at or above LLQ.
Total Body Clearance (CL) of EMD 525797: After Single Dose
Time frame: Pre-dose, hour 1 (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 1
Total body clearance of drug in serum was calculated: as CL= Dose divided by Area under the serum concentration-time curve from time zero to infinity (AUC0-inf).
Total Body Clearance at Steady State (CLss) of EMD 525797
Time frame: Pre-dose, hour 1 (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 5
Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. CL of drug in serum was calculated as : CL= Dose/ AUC0-inf. Area under the serum concentration-time curve from time zero to infinity (AUC0-inf), calculated as AUC0-t + AUCextra. AUCextra represents an extrapolated value obtained by Clast / λz, where Clast is the calculated serum concentration at the last sampling time point at which the measured serum concentration is at or above LLQ and λz is the elimination rate constant.
Apparent Volume of Distribution (Vz): After Single Dose
Time frame: Pre-dose, hour 1 (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 1
Apparent volume of distribution during the terminal phase, calculated as Vz = Dose/AUC0-inf multiplied by elimination rate constant [λz]) following single dose. Area under the serum concentration-time curve from time zero to infinity, calculated (AUC0-inf) as AUC0-t + AUCextra. AUCextra represents an extrapolated value obtained by Clast / λz, where Clast is the calculated serum concentration at the last sampling time point at which the measured serum concentration is at or above LLQ and λz is the elimination rate constant. And the elimination rate constant obtained from linear regression of the terminal phase of the log transformed concentration-time data. A minimum of three points is required to calculate λz.
Pharmacokinetics of EMD 525797 - Trough Values
Time frame: Pre-dose, hour 1 (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 5
The observed serum concentration immediately before next dosing determined directly from the serum concentration-time profile of each subject (= trough concentration).
Apparent Volume of Distribution: After Multiple Dose
Time frame: Pre-dose, hour 1 (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 5
Apparent volume of distribution during the terminal phase, calculated as Vz = Dose/(Area under the serum concentration-time curve within one complete dosing interval [AUCtau]* λz) following multiple dose.

19 secondary outcomes

Number of Subjects With Overall Tumor Response
Time frame: Baseline up to Week 36
Number of Subjects With Clinical Benefit
Time frame: Baseline up to Week 36
Progression-free Survival (PFS)
Time frame: From first dosing date until disease progression or death, maximum up to Week 36
Apparent Terminal Half Life (t1/2): After Single Dose
Time frame: Pre-dose, end of infusion (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 1
Apparent Terminal Half Life (t1/2): After Multiple Dose
Time frame: Pre-dose, EOI, 4, 8, 24, 48, and 96 hours after start of infusion at Week 5
Time to Maximum Observed Serum Concentration (Tmax): After Single Dose
Time frame: Pre-dose, end of infusion (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 1
Time to Maximum Observed Serum Concentration (Tmax): After Multiple Dose
Time frame: Pre-dose, EOI, 4, 8, 24, 48, and 96 hours after start of infusion at Week 5
Elimination Rate Constant (λz): After Single Dose
Time frame: Pre-dose, end of infusion (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 1
Elimination Rate Constant ( λ z): After Multiple Dose
Time frame: Pre-dose, EOI, 4, 8, 24, 48, and 96 hours after start of infusion at Week 5
Minimum Observed Serum Concentration (Cmin) After Multiple Doses
Time frame: Pre-dose, EOI, 4, 8, 24, 48, and 96 hours after start of infusion at Week 5
Observed Serum Concentration Immediately Before Next Dosing (Cpre)
Time frame: Pre-dose, EOI, 4, 8, 24, 48, and 96 hours after start of infusion at Week 5
Average Serum Concentration at Steady State (Cav)
Time frame: Pre-dose, EOI, 4, 8, 24, 48, and 96 hours after start of infusion at Week 5
Area Under the Serum Concentration-time Curve Within One Complete Dosing Interval( AUCtau): After Single Dose
Time frame: Pre-dose, end of infusion (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 1
Area Under the Serum Concentration-time Curve Within One Complete Dosing Interval( AUCtau): After Multiple Dose
Time frame: Pre-dose, EOI, 4, 8, 24, 48, and 96 hours after start of infusion at Week 5
Volume of Distribution at Steady State (Vss)
Time frame: Pre-dose, EOI, 4, 8, 24, 48, and 96 hours after start of infusion at Week 5
Mean Residency Time (MRT0-inf)
Time frame: Pre-dose, end of infusion (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 1
Mean Residence Time at Steady State (MRTss)
Time frame: Pre-dose, EOI, 4, 8, 24, 48, and 96 hours after start of infusion at Week 5
Percentage Peak-Trough Fluctuation (PTF)
Time frame: Pre-dose, EOI, 4, 8, 24, 48, and 96 hours after start of infusion at Week 5
Accumulation Ratio (Rac)
Time frame: Pre-dose, end of infusion (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 1 and Week 5

Results and safety

Results posted to the registry on 13 May 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
EMD525797 250 mg	8	8
EMD525797 500 mg	6	6
EMD525797 1000 mg	6	6
EMD525797 1500 mg	7	7

Primary outcome: Number of Subjects With Dose-limiting Toxicities (DLTs)

Time frame: Baseline up to Week 4. Number. Unit: subjects

Measure	EMD525797 250 mg n = 8	EMD525797 500 mg n = 6	EMD525797 1000 mg n = 6	EMD525797 1500 mg n = 6
Value	0	0	0	0

Population analysed: Dose escalation analysis set/DLT analysis set included all subjects who experienced a DLT or subjects who did not experience a DLT and had a relative dose intensity of \>= 75 percent (%) during the DLT observation period.

Primary outcome: Maximum Observed Serum Concentration (Cmax): After Single Dose

Time frame: Pre-dose, hour 1(end of infusion [EOI]), 4, 8, 24, 48, and 96 hours after start of infusion at Week 1. Geometric mean (Geometric Coefficient of Variation). Unit: microgram per milliliter (mcg/mL)

Measure	EMD525797 250 mg n = 8	EMD525797 500 mg n = 6	EMD525797 1000 mg n = 6	EMD525797 1500 mg n = 7
Value	73.12 (12.1)	162.48 (15.2)	419.26 (16.4)	683.46 (28.0)

Population analysed: The pharmacokinetic (PK) analysis set included all subjects who received at least the first dose of the study drug and who provided sufficient data for a concentration-time profile for EMD 525797.

Primary outcome: Maximum Observed Serum Concentration (Cmax) of EMD 525797:After Multiple Dose

Time frame: Pre-dose, hour 1 (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 5. Geometric mean (Geometric Coefficient of Variation). Unit: mcg/mL

Measure	EMD525797 250 mg n = 6	EMD525797 500 mg n = 6	EMD525797 1000 mg n = 6	EMD525797 1500 mg n = 6
Value	89.336 (6.6)	198.728 (20.1)	680.022 (18.1)	1170.73 (22.2)

Population analysed: The PK analysis set included all subjects who received at least the first dose of the study drug and who provided sufficient data for a concentration-time profile for EMD 525797. Here N (number of subjects analyzed) signifies the total number of subjects evaluable for this outcome measure.

Primary outcome: Area Under the Curve From Time Zero to Last Quantifiable Concentration(AUC0-t) of EMD 525797: After Single Dose

Time frame: Pre-dose, hour 1 (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 1. Geometric mean (Geometric Coefficient of Variation). Unit: hour*mcg/mL

Measure	EMD525797 250 mg n = 8	EMD525797 500 mg n = 6	EMD525797 1000 mg n = 6	EMD525797 1500 mg n = 7
Value	7942.6 (19.6)	21562.3 (14.0)	67545.6 (18.9)	95369.6 (40.9)

Population analysed: The PK analysis set included all subjects who received at least the first dose of the study drug and who provided sufficient data for a concentration-time profile for EMD 525797.

19 secondary outcomes are reported in the full results.

Adverse events

Time frame: First dose of the study drug up to 31+/-3 days after the last administration of EMD 525797, assessed upto maximum of 22 months.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
EMD525797 250 mg	1 of 8 (12.5%)	8 of 8 (100%)	Not reported
EMD525797 500 mg	1 of 6 (16.7%)	6 of 6 (100%)	Not reported
EMD525797 1000 mg	1 of 6 (16.7%)	6 of 6 (100%)	Not reported
EMD525797 1500 mg	1 of 7 (14.3%)	7 of 7 (100%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 13 May 2016.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Responsible study director

Merck Serono Co., Ltd., Japan

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing EMD525797 in people with Solid Tumor, run by Merck KGaA, Darmstadt, Germany at 1 site in Japan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 May 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 May 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Subjects With Dose-limiting Toxicities (DLTs) (time frame: Baseline up to Week 4). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01327313.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 May 2016.