A Study of EMD525797 in Solid Tumor Patients in Japan

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck KGaA
ClinicalTrials.gov Identifier:
NCT01327313
First received: March 30, 2011
Last updated: June 13, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Solid Tumor
Biological: EMD525797
Phase 1

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

Resource links provided by NLM:


Further study details as provided by Merck KGaA:

Primary Outcome Measures:
  • 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. [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]

    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.


  • Pharmacokinetics of EMD 525797 - Cmax [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Observed maximum serum concentration

  • Pharmacokinetics of EMD 525797 - AUC0-t [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    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

  • Pharmacokinetics of EMD 525797 - CL [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Total body clearance of drug from serum

  • Pharmacokinetics of EMD 525797 - Vz [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Apparent volume of distribution during the terminal phase

  • Pharmacokinetics of EMD 525797 - trough values [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall tumor response - complete or partial response [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Number of participants with at least one confirmed CR or PR according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.0

  • Clinical benefit - complete or partial response, or stable disease [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Number of participants with at least one confirmed CR, PR, or SD lasting at least 12 weeks according to RECIST version 1.0

  • Progression-free survival [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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.

  • Pharmacokinetics of EMD 525797 - t1/2 [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Apparent terminal half-life

  • Pharmacokinetics of EMD 525797 - tmax [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Time to reach Cmax

  • Pharmacokinetics of EMD 525797 - λz [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    The elimination rate constant obtained from linear regression of the terminal phase of the log transformed concentration-time data

  • Pharmacokinetics of EMD 525797 - Cmin [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Observed minimum serum concentration during a dosing interval

  • Pharmacokinetics of EMD 525797 - Cpre [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Observed serum concentration immediately before next dosing

  • Pharmacokinetics of EMD 525797 - Cav [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Average serum concentration at steady state

  • Pharmacokinetics of EMD 525797 - AUCτ [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Plasma concentration at the end of an intravenous infusion

  • Pharmacokinetics of EMD 525797 - Vss [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Apparent volume of distribution at steady state

  • Pharmacokinetics of EMD 525797 - MRT [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Mean residence time of drug in the body

  • Pharmacokinetics of EMD 525797 - Percentage PTF [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Peak trough fluctuation

  • Pharmacokinetics of EMD 525797 - Accumulation ratio [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

Enrollment: 30
Study Start Date: January 2011
Study Completion Date: October 2012
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1 Biological: EMD525797
250mg of EMD525797 intravenously every 2 weeks, until DLT, PD or unacceptable toxicity develops.
Experimental: Arm 2 Biological: EMD525797
500mg of EMD525797 intravenously every 2 weeks, until DLT, PD or unacceptable toxicity develops.
Experimental: Arm 3 Biological: EMD525797
1000 mg of EMD525797 intravenously every 2 weeks, until DLT, PD or unacceptable toxicity develops.
Experimental: Arm 4 Biological: EMD525797
1500 mg of EMD525797 intravenously every 2 weeks, until DLT, PD or unacceptable toxicity develops.

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01327313

Locations
Japan
For Recruiting
Locations in, Japan
Sponsors and Collaborators
Merck KGaA
  More Information

No publications provided

Responsible Party: Merck KGaA
ClinicalTrials.gov Identifier: NCT01327313     History of Changes
Other Study ID Numbers: EMR200017-007
Study First Received: March 30, 2011
Last Updated: June 13, 2014
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency

Keywords provided by Merck KGaA:
alpha v integrin
antibody
solid tumor
Japanese

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on August 25, 2014