Clinical trial NCT01327313: A Study of EMD525797 in Solid Tumor Patients in Japan
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumor
Keywords: alpha v integrin
antibody
solid tumor
Japanese
EMD525797
Lead sponsor: Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
First posted: 2011-04-01
Enrollment: 27
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: Inclusion Criteria:

* 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
* 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

Exclusion Criteria:

* 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
* 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

Primary outcomes:
measure: Number of Subjects With Dose-limiting Toxicities (DLTs)
timeFrame: Baseline up to Week 4
measure: Maximum Observed Serum Concentration (Cmax): After Single Dose
timeFrame: Pre-dose, hour 1(end of infusion [EOI]), 4, 8, 24, 48, and 96 hours after start of infusion at Week 1
measure: Maximum Observed Serum Concentration (Cmax) of EMD 525797:After Multiple Dose
timeFrame: Pre-dose, hour 1 (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 5
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration(AUC0-t) of EMD 525797: After Single Dose
timeFrame: Pre-dose, hour 1 (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 1
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration(AUC0-t) of EMD 525797: After Multiple Dose
timeFrame: Pre-dose, hour 1 (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 5
measure: Total Body Clearance (CL) of EMD 525797: After Single Dose
timeFrame: Pre-dose, hour 1 (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 1
measure: Total Body Clearance at Steady State (CLss) of EMD 525797
timeFrame: Pre-dose, hour 1 (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 5
measure: Apparent Volume of Distribution (Vz): After Single Dose
timeFrame: Pre-dose, hour 1 (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 1
measure: Pharmacokinetics of EMD 525797 - Trough Values
timeFrame: Pre-dose, hour 1 (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 5
measure: Apparent Volume of Distribution: After Multiple Dose
timeFrame: Pre-dose, hour 1 (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 5
Secondary outcomes:
measure: Number of Subjects With Overall Tumor Response
timeFrame: Baseline up to Week 36
measure: Number of Subjects With Clinical Benefit
timeFrame: Baseline up to Week 36
measure: Progression-free Survival (PFS)
timeFrame: From first dosing date until disease progression or death, maximum up to Week 36
measure: Apparent Terminal Half Life (t1/2): After Single Dose
timeFrame: Pre-dose, end of infusion (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 1
measure: Apparent Terminal Half Life (t1/2): After Multiple Dose
timeFrame: Pre-dose, EOI, 4, 8, 24, 48, and 96 hours after start of infusion at Week 5
measure: Time to Maximum Observed Serum Concentration (Tmax): After Single Dose
timeFrame: Pre-dose, end of infusion (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 1
measure: Time to Maximum Observed Serum Concentration (Tmax): After Multiple Dose
timeFrame: Pre-dose, EOI, 4, 8, 24, 48, and 96 hours after start of infusion at Week 5
measure: Elimination Rate Constant (λz): After Single Dose
timeFrame: Pre-dose, end of infusion (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 1
measure: Elimination Rate Constant ( λ z): After Multiple Dose
timeFrame: Pre-dose, EOI, 4, 8, 24, 48, and 96 hours after start of infusion at Week 5
measure: Minimum Observed Serum Concentration (Cmin) After Multiple Doses
timeFrame: Pre-dose, EOI, 4, 8, 24, 48, and 96 hours after start of infusion at Week 5
measure: Observed Serum Concentration Immediately Before Next Dosing (Cpre)
timeFrame: Pre-dose, EOI, 4, 8, 24, 48, and 96 hours after start of infusion at Week 5
measure: Average Serum Concentration at Steady State (Cav)
timeFrame: Pre-dose, EOI, 4, 8, 24, 48, and 96 hours after start of infusion at Week 5
measure: Area Under the Serum Concentration-time Curve Within One Complete Dosing Interval( AUCtau): After Single Dose
timeFrame: Pre-dose, end of infusion (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 1
measure: Area Under the Serum Concentration-time Curve Within One Complete Dosing Interval( AUCtau): After Multiple Dose
timeFrame: Pre-dose, EOI, 4, 8, 24, 48, and 96 hours after start of infusion at Week 5
measure: Volume of Distribution at Steady State (Vss)
timeFrame: Pre-dose, EOI, 4, 8, 24, 48, and 96 hours after start of infusion at Week 5
measure: Mean Residency Time (MRT0-inf)
timeFrame: Pre-dose, end of infusion (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 1
measure: Mean Residence Time at Steady State (MRTss)
timeFrame: Pre-dose, EOI, 4, 8, 24, 48, and 96 hours after start of infusion at Week 5
measure: Percentage Peak-Trough Fluctuation (PTF)
timeFrame: Pre-dose, EOI, 4, 8, 24, 48, and 96 hours after start of infusion at Week 5
measure: Accumulation Ratio (Rac)
timeFrame: Pre-dose, end of infusion (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 1 and Week 5
Other outcomes:
Locations:
city: Locations in
country: Japan
facility: For Recruiting
Study officials:
affiliation: Merck Serono Co., Ltd., Japan
name: Medical Responsible
role: STUDY_DIRECTOR
References: