A Study of EMD525797 in Solid Tumor Patients in Japan

NCT01327313 | Completed Phase 1 Results

• 1 other identifier: EMR200017-007
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

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.

Conditions

Solid Tumor

Keywords

alpha v integrin; antibody; solid tumor; Japanese; EMD525797

Outcome Measures

Primary Outcomes (10)

• 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.

  Baseline up to Week 4

• Maximum Observed Serum Concentration (Cmax): After Single Dose

  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

  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).

  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.

  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).

  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.

  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.

  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).

  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.

  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

  Baseline up to Week 36

• Number of Subjects With Clinical Benefit

  Baseline up to Week 36

• Progression-free Survival (PFS)

  From first dosing date until disease progression or death, maximum up to Week 36

• Apparent Terminal Half Life (t1/2): After Single Dose

  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

  Pre-dose, EOI, 4, 8, 24, 48, and 96 hours after start of infusion at Week 5

Study Arms (4)

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

Interventions

EMD525797 BIOLOGICAL

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

EMD525797 250 milligram (mg)

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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;
• 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

Sponsors & Collaborators

• Merck KGaA, Darmstadt, Germany: lead

Study Sites (1)

For Recruiting

Locations in, Japan

Location

Results Point of Contact

• Title: Merck KGaA Communication Center
• Organization: Merck Serono, a division of Merck KGaA

service@merckgroup.com

+49-6151-72-5200

Study Officials

• Medical Responsible

  Merck Serono Co., Ltd., Japan

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 30, 2011
• First Posted: April 1, 2011
• Study Start: January 1, 2011
• Primary Completion: July 1, 2012
• Study Completion: October 1, 2012
• Last Updated: May 13, 2016
• Results First Posted: May 13, 2016

Record last verified: 2016-04

Locations

JP (1)