A Study of EMD525797 in Solid Tumor Patients in Japan

Solid Tumor Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01327313
• Other study ID #: EMR200017-007
• Status: Completed
• Phase: Phase 1
• First received: March 30, 2011
• Last updated: June 13, 2014
• Start date: January 2011
• Est. completion date: October 2012

Study information

• Verified date: June 2014
• Source: Merck KGaA
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Pharmaceuticals and Medical Devices Agency
• Study type: Interventional

Clinical Trial Summary

The primary objectives are to assess the safety and tolerability of single and repeated doses of EMD525797, and characterize PK of following single and repeated doses. The secondary objectives are to investigate the immunogenicity and PD, and to assess the anti-tumor activity of EMD525797.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: October 2012
• Est. primary completion date: July 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years and older

Eligibility

Inclusion Criteria:

• Age = 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 RECIST version 1.0. Complete tumor assessment to be performed within the 30 days prior to the first EMD 525797 administration;

• ECOG performance status of 0 to 1;

• Estimated life expectancy of at least 3 months;

• Absolute Neutrophil Count (ANC) = 1.5 x 109/L;

• Platelets = 100 x 109/L;

• Hemoglobin = 9.0 g/dL (without transfusions);

• Total bilirubin = 1.5 x upper limit of normal (ULN);

• Aspartate transaminase (AST), alanine transaminase (ALT) = 3 x ULN;

• In subjects with hepatic metastasis, total bilirubin = 3 x UNL, AST and ALT = 5 x UNL;

• Prothrombin time (PT), prothrombin time/international normalized ratio (PT/INR), and activated partial thromboplastin time (APTT) within normal limits;

• Creatinine clearance = 50 mL/min

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 EMD 525797), clinically significant unhealed wound, or unrecovered bone fracture;

• Chronic doses of oral steroids, defined as = 10 mg of prednisone equivalents per day;

• Confirmed or clinically suspected brain or leptomeningeal metastases;

• Known hypersensitivity to EMD 525797 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 EMD 525797;

• Uncontrolled diabetes;

• Uncontrolled hypertension defined as systolic blood pressure = 160 mmHg and/or diastolic blood pressure = 100 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)

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Solid Tumor

Intervention

Biological:
• EMD525797
250mg of EMD525797 intravenously every 2 weeks, until DLT, PD or unacceptable toxicity develops.
• EMD525797
500mg of EMD525797 intravenously every 2 weeks, until DLT, PD or unacceptable toxicity develops.
• EMD525797
1000 mg of EMD525797 intravenously every 2 weeks, until DLT, PD or unacceptable toxicity develops.
• EMD525797
1500 mg of EMD525797 intravenously every 2 weeks, until DLT, PD or unacceptable toxicity develops.

Locations

Country	Name	City	State
Japan	For Recruiting	Locations in

Sponsors (1)

Lead Sponsor	Collaborator
Merck KGaA

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose-limiting toxicities (DLTs) occurring during the first 4 weeks of treatment, using the National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0.	Any Grade 3 or 4 hematological or non-hematological toxicity (with the exception of toxicities detailed below) 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 are reversible within 7 days, unless the Investigator decides this event is clinically significant.	4 weeks	No
Primary	Pharmacokinetics of EMD 525797 - Cmax	Observed maximum serum concentration	8 weeks	No
Primary	Pharmacokinetics of EMD 525797 - AUC0-t	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	8 weeks	No
Primary	Pharmacokinetics of EMD 525797 - CL	Total body clearance of drug from serum	8 weeks	No
Primary	Pharmacokinetics of EMD 525797 - Vz	Apparent volume of distribution during the terminal phase	8 weeks	No
Primary	Pharmacokinetics of EMD 525797 - trough values		8 weeks	No
Secondary	Overall tumor response - complete or partial response	Number of participants with at least one confirmed CR or PR according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.0	From first dosing date until complete response (CR) or partial response (PR), reported between day of first patient participation, Dec 2010, until cut-off date expected Dec 2012	No
Secondary	Clinical benefit - complete or partial response, or stable disease	Number of participants with at least one confirmed CR, PR, or SD lasting at least 12 weeks according to RECIST version 1.0	From first dosing date until CR, PR, or stable disease (SD), reported between day of first patient participation, Dec 2010, until cut-off date expected Dec 2012	No
Secondary	Progression-free survival	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.	From first dosing date until disease progression or death, reported between day of first patient participation, Dec 2010, until cut-off date expected Dec 2012	No
Secondary	Pharmacokinetics of EMD 525797 - t1/2	Apparent terminal half-life	8 weeks	No
Secondary	Pharmacokinetics of EMD 525797 - tmax	Time to reach Cmax	8 weeks	No
Secondary	Pharmacokinetics of EMD 525797 - ?z	The elimination rate constant obtained from linear regression of the terminal phase of the log transformed concentration-time data	8 weeks	No
Secondary	Pharmacokinetics of EMD 525797 - Cmin	Observed minimum serum concentration during a dosing interval	8 weeks	No
Secondary	Pharmacokinetics of EMD 525797 - Cpre	Observed serum concentration immediately before next dosing	8 weeks	No
Secondary	Pharmacokinetics of EMD 525797 - Cav	Average serum concentration at steady state	8 weeks	No
Secondary	Pharmacokinetics of EMD 525797 - AUCt	Plasma concentration at the end of an intravenous infusion	8 weeks	No
Secondary	Pharmacokinetics of EMD 525797 - Vss	Apparent volume of distribution at steady state	8 weeks	No
Secondary	Pharmacokinetics of EMD 525797 - MRT	Mean residence time of drug in the body	8 weeks	No
Secondary	Pharmacokinetics of EMD 525797 - Percentage PTF	Peak trough fluctuation	8 weeks	No
Secondary	Pharmacokinetics of EMD 525797 - Accumulation ratio		8 weeks	No