search
Back to results

EMD 525797 in Colorectal and Ovarian Cancer Patients With Liver Metastases

Primary Purpose

Colorectal and Ovarian Cancer Patients With Liver Metastases

Status
Completed
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
EMD 525797
Sponsored by
Merck KGaA, Darmstadt, Germany
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Colorectal and Ovarian Cancer Patients With Liver Metastases

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Provision of signed written informed consent
  • Male or female subjects, aged at least 18 years
  • Subjects with liver metastases (3 to 10 centimeter [cm] diameter) from colorectal and ovarian cancers
  • Failure of standard cancer therapy
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 at study entry and an estimated life expectancy of at least 3 months
  • Adequate haematological function, defined by absolute neutrophil count (ANC) greater than or equal to (>=) 1.5 x 10^9 per liter (/L), platelet count >= 100 x 10^9 / L, and haemoglobin concentration >= 9 gram per deciliter (g/dL)
  • As subjects with documented liver metastases are treated in this trial, liver function test values are accepted as followed: up to the upper limit of Grade 2 as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0. This includes total bilirubin level less than or equal to (=<) 3 times the upper limit of normal (ULN), and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels =<5 x ULN
  • Adequate renal function defined by serum creatinine =<1.5 x ULN or a creatinine clearance of >=50 milliliter per minute (mL/min) calculated by Cockcroft-Gault
  • Effective contraception (example: double barrier method) for both male and female subjects if the risk of conception exists. These subjects must be willing to avoid pregnancy during the study (screening to end of study [EOS]) as well as for at least 3 months after the last dosing.

Exclusion Criteria:

  • Any systemic cancer treatment within 30 days before treatment with EMD 525797
  • Thrombolytics or oral or parenteral anticoagulants (except to maintain patency of preexisting, permanent indwelling intravenous catheters) within 10 days prior to study start and during treatment
  • Radiotherapy, chemotherapy, surgery, or any investigational drug in the 30 days before the start of treatment in this study, and/or diagnostic biopsies within 2 weeks before the start of treatment in this study
  • Previous treatment with anti-integrin therapy or anti angiogenic therapy within the last 6 months
  • Confirmed or clinically suspected brain metastases
  • Known hypersensitivity reactions to the study medication
  • History of allergic reactions to other monoclonal antibody (mAb) therapy
  • Uncontrolled hypertension (systolic blood pressure greater than (>) 180 millimeter of mercury (mmHg), diastolic >100 mmHg)
  • Current history of chronic daily aspirin therapy (doses of =< 150 mg is permitted), bleeding disorders, and/or history of thromboembolic events
  • Severe peripheral vascular disease or ulceration
  • Unstable angina pectoris, or myocardial infarction within 6 months before start of study treatment, clinical significant abnormal electrocardiogram (ECG) at screening;
  • In women of childbearing potential, pregnancy (absence to be confirmed by beta human chorionic gonadotropin [β HCG] test, unless a subject has previously undergone hysterectomy or bilateral ovariectomy), or lactation period
  • Known alcohol or drug abuse
  • Participation in another clinical trial within the past 30 days before start of study treatment
  • All other significant diseases which, in the opinion of the principal investigator (PI), might impair the subject's tolerance of study treatment
  • Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent
  • Legal incapacity or limited legal capacity (not applicable only in rare cases)
  • Known human immuno deficiency (HIV) infection and/or active hepatitis B or C virus infections
  • Ongoing uncontrolled infections
  • Contraindications to magnetic resonance imaging (MRI)

Sites / Locations

  • Christie Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

EMD 525797

Arm Description

Outcomes

Primary Outcome Measures

Number of Subjects With Dose Limiting Toxicities (DLTs)
Toxicity was graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0. A DLT was defined as any Grade 3 or 4 haematological or non-haematological toxicity occurring during the first 4 weeks of treatment (that is, until the beginning of Week 5, with the exception of Grade 3 asymptomatic increase in liver function tests (aspartate aminotransferase [AST], alanine aminotransferase [ALT], and alkaline phosphatase [ALP]) returning to Baseline within 7 days.), at any dose level, for which a causal relationship to the investigative medicinal product could not be ruled out by the Investigator and/or the Sponsor.
Volume Transfer Coefficient of Contrast Agent Across the Capillary Walls
Volume transfer coefficient was defined as the volume transfer coefficient of contrast agent across the capillary wall, reflecting endothelial permeability and blood flow. Volumetric transfer coefficient was measured by dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). DCE-MRI is a noninvasive quantitative method of investigating microvascular structure and function by tracking the pharmacokinetics of injected low molecular weight contrast agents as they pass through tumor vasculature.
Blood Plasma Volume and Extravascular/Extracellular Volume
Blood plasma volume and extracellular/extravascular volume was measured using DCE-MRI.
Initial Area Under the DCE-MRI Contrast Agent Concentration Time Curve After 60 Seconds (IAUC60)
IAUC 60 was used to give a gross indication of the delivery and uptake of contrast agent within the tumor (indicating the degree of perfusion and endothelial permeability. IAUC60 was measured using DCE-MRI.
Whole Tumor Volume and Enhancing Tumor Volume
Tumor volume (three-dimensional measurement) and the enhancing fraction of the tumor, which provides a gross measure of the proportion of the tumor that has a measurable level of perfusion, were assessed using DCE-MRI.

Secondary Outcome Measures

Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation and TEAEs Leading to Death
An adverse event (AE) was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/ significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAEs were the AEs that occurred between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state.
Number of Subjects With Best Overall Response, Tumor Response and Clinical Benefit
Tumor response was assessed by the Investigator, based on Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.0 criteria. Tumor response was defined as the presence of a "best overall response" of complete response (CR) or partial response (PR). CR: Disappearance of all target and non-target lesions and/or normalization of serum levels of tumor markers. PR: At least a 30 percent decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum of the LD of target lesions. The qualification of a CR or of a PR needed a confirmation by a second computed tomography (CT) scan at least 4 weeks after the first scan. Best overall response was derived programmatically as the best response recorded from the first investigation medicinal product administration until disease progression. Clinical benefit was defined as the presence of a "best overall response" of complete response or partial response or stable disease lasting at least 6 weeks.
Number of Subjects With Worsened Post Baseline Shift in ECOG Performance Status Score
The number of subjects who experienced worse post baseline shift were assessed as per ECOG performance status score recorded during the treatment. The ECOG score is categorized as Grade 0, 1, 2, 3 and 4 where Grade 0=fully active, Grade 1=restricted in physically strenuous activity, Grade 2=unable to carry out any work activities, Grade 3=capable of only limited self-care and Grade 4=completely disabled.
Number of Subjects With Positive Binding Abituzumab Antibodies
Subjects were defined as abituzumab positive if at least one positive result of antibodies against abituzumab was observed. In all other cases, subjects were defined as abituzumab negative.
Progression-Free Survival (PFS) Time
PFS was defined as the time from first study drug intake until radiological progression (based on RECIST Version 1.0) or death due to any cause. Only deaths within 84 days of last tumor assessment are considered. Subjects without event were censored on the date of last tumor assessment. Investigator read was the assessment of all imaging by the treating physician at the local trial site.

Full Information

First Posted
February 19, 2009
Last Updated
November 9, 2015
Sponsor
Merck KGaA, Darmstadt, Germany
search

1. Study Identification

Unique Protocol Identification Number
NCT00848510
Brief Title
EMD 525797 in Colorectal and Ovarian Cancer Patients With Liver Metastases
Official Title
A Phase I, Open-label, Dose-escalation Study to Investigate the Safety, Tolerability, PD and PK of EMD 525797 Using DCE-MRI as a PK Measure of Response in Colorectal and Ovarian Cancer Patients With Liver Metastases After Failure of Standard Therapy
Study Type
Interventional

2. Study Status

Record Verification Date
November 2015
Overall Recruitment Status
Completed
Study Start Date
February 2009 (undefined)
Primary Completion Date
November 2013 (Actual)
Study Completion Date
November 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck KGaA, Darmstadt, Germany

4. Oversight

5. Study Description

Brief Summary
This study is intended to test an experimental drug called EMD 525797 (Abituzumab). This drug is not yet approved for sale and has only been tested in a small number of people to date (prior to this study starting another research study was carried out involving 37 healthy volunteers receiving the study drug). Until more is known about this study drug, it can only be used in research studies. This research study is planned to answer important questions about how the study drug is tolerated and how it may work in subjects with ovarian and colorectal cancer which has spread to the liver (i.e. metastatic cancer). The Sponsor (Merck KGaA) of this study is developing the study drug.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal and Ovarian Cancer Patients With Liver Metastases

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
41 (Actual)

8. Arms, Groups, and Interventions

Arm Title
EMD 525797
Arm Type
Experimental
Intervention Type
Biological
Intervention Name(s)
EMD 525797
Intervention Description
Abituzumab will be administered as an intravenous infusion for an hour at a dose of 250 milligram (mg) to 1500 mg at Weeks 1, 3 and 5. In case of clinical benefit (stable disease [SD], complete response [CR], or partial response [PR]) that will be assessed by the Response Evaluation Criteria in Solid Tumors (RECIST Version 1.0) during initial 6 Weeks, subjects will be allowed to continue treatment at the start of Week 7 at the given dose (250 mg or 500 mg or 1000 mg or 1500 mg) every second week until intolerance to treatment, withdrawal of consent, or the subject is no longer benefiting from treatment in the opinion of the Investigator.
Primary Outcome Measure Information:
Title
Number of Subjects With Dose Limiting Toxicities (DLTs)
Description
Toxicity was graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0. A DLT was defined as any Grade 3 or 4 haematological or non-haematological toxicity occurring during the first 4 weeks of treatment (that is, until the beginning of Week 5, with the exception of Grade 3 asymptomatic increase in liver function tests (aspartate aminotransferase [AST], alanine aminotransferase [ALT], and alkaline phosphatase [ALP]) returning to Baseline within 7 days.), at any dose level, for which a causal relationship to the investigative medicinal product could not be ruled out by the Investigator and/or the Sponsor.
Time Frame
Up to Week 4
Title
Volume Transfer Coefficient of Contrast Agent Across the Capillary Walls
Description
Volume transfer coefficient was defined as the volume transfer coefficient of contrast agent across the capillary wall, reflecting endothelial permeability and blood flow. Volumetric transfer coefficient was measured by dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). DCE-MRI is a noninvasive quantitative method of investigating microvascular structure and function by tracking the pharmacokinetics of injected low molecular weight contrast agents as they pass through tumor vasculature.
Time Frame
Screening 1, screening 2, Week 1 Day 2, Week 1 Day 5, and Week 2 Day 1
Title
Blood Plasma Volume and Extravascular/Extracellular Volume
Description
Blood plasma volume and extracellular/extravascular volume was measured using DCE-MRI.
Time Frame
Screening 1, screening 2, Week 1 Day 2, Week 1 Day 5, and Week 2 Day 1
Title
Initial Area Under the DCE-MRI Contrast Agent Concentration Time Curve After 60 Seconds (IAUC60)
Description
IAUC 60 was used to give a gross indication of the delivery and uptake of contrast agent within the tumor (indicating the degree of perfusion and endothelial permeability. IAUC60 was measured using DCE-MRI.
Time Frame
Screening 1, screening 2, Week 1 Day 2, Week 1 Day 5, and Week 2 Day 1
Title
Whole Tumor Volume and Enhancing Tumor Volume
Description
Tumor volume (three-dimensional measurement) and the enhancing fraction of the tumor, which provides a gross measure of the proportion of the tumor that has a measurable level of perfusion, were assessed using DCE-MRI.
Time Frame
Screening 1, screening 2, Week 1 Day 2, Week 1 Day 5, and Week 2 Day 1
Secondary Outcome Measure Information:
Title
Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation and TEAEs Leading to Death
Description
An adverse event (AE) was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/ significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAEs were the AEs that occurred between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state.
Time Frame
From the initiation of the trial treatment until 30 days after last administration of trial treatment.
Title
Number of Subjects With Best Overall Response, Tumor Response and Clinical Benefit
Description
Tumor response was assessed by the Investigator, based on Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.0 criteria. Tumor response was defined as the presence of a "best overall response" of complete response (CR) or partial response (PR). CR: Disappearance of all target and non-target lesions and/or normalization of serum levels of tumor markers. PR: At least a 30 percent decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum of the LD of target lesions. The qualification of a CR or of a PR needed a confirmation by a second computed tomography (CT) scan at least 4 weeks after the first scan. Best overall response was derived programmatically as the best response recorded from the first investigation medicinal product administration until disease progression. Clinical benefit was defined as the presence of a "best overall response" of complete response or partial response or stable disease lasting at least 6 weeks.
Time Frame
Up to 4 years
Title
Number of Subjects With Worsened Post Baseline Shift in ECOG Performance Status Score
Description
The number of subjects who experienced worse post baseline shift were assessed as per ECOG performance status score recorded during the treatment. The ECOG score is categorized as Grade 0, 1, 2, 3 and 4 where Grade 0=fully active, Grade 1=restricted in physically strenuous activity, Grade 2=unable to carry out any work activities, Grade 3=capable of only limited self-care and Grade 4=completely disabled.
Time Frame
Up to 4 weeks after last dose administration
Title
Number of Subjects With Positive Binding Abituzumab Antibodies
Description
Subjects were defined as abituzumab positive if at least one positive result of antibodies against abituzumab was observed. In all other cases, subjects were defined as abituzumab negative.
Time Frame
Day 1 of Weeks 1, 3, 5, 6, 7, 8, and week 11 and end of study (EOS) visit (4 weeks after last dose administration)
Title
Progression-Free Survival (PFS) Time
Description
PFS was defined as the time from first study drug intake until radiological progression (based on RECIST Version 1.0) or death due to any cause. Only deaths within 84 days of last tumor assessment are considered. Subjects without event were censored on the date of last tumor assessment. Investigator read was the assessment of all imaging by the treating physician at the local trial site.
Time Frame
Time from first study drug intake to disease progression, death or last tumor assessment until end of trial visit (4 weeks after last dose administration)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Provision of signed written informed consent Male or female subjects, aged at least 18 years Subjects with liver metastases (3 to 10 centimeter [cm] diameter) from colorectal and ovarian cancers Failure of standard cancer therapy Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 at study entry and an estimated life expectancy of at least 3 months Adequate haematological function, defined by absolute neutrophil count (ANC) greater than or equal to (>=) 1.5 x 10^9 per liter (/L), platelet count >= 100 x 10^9 / L, and haemoglobin concentration >= 9 gram per deciliter (g/dL) As subjects with documented liver metastases are treated in this trial, liver function test values are accepted as followed: up to the upper limit of Grade 2 as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0. This includes total bilirubin level less than or equal to (=<) 3 times the upper limit of normal (ULN), and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels =<5 x ULN Adequate renal function defined by serum creatinine =<1.5 x ULN or a creatinine clearance of >=50 milliliter per minute (mL/min) calculated by Cockcroft-Gault Effective contraception (example: double barrier method) for both male and female subjects if the risk of conception exists. These subjects must be willing to avoid pregnancy during the study (screening to end of study [EOS]) as well as for at least 3 months after the last dosing. Exclusion Criteria: Any systemic cancer treatment within 30 days before treatment with EMD 525797 Thrombolytics or oral or parenteral anticoagulants (except to maintain patency of preexisting, permanent indwelling intravenous catheters) within 10 days prior to study start and during treatment Radiotherapy, chemotherapy, surgery, or any investigational drug in the 30 days before the start of treatment in this study, and/or diagnostic biopsies within 2 weeks before the start of treatment in this study Previous treatment with anti-integrin therapy or anti angiogenic therapy within the last 6 months Confirmed or clinically suspected brain metastases Known hypersensitivity reactions to the study medication History of allergic reactions to other monoclonal antibody (mAb) therapy Uncontrolled hypertension (systolic blood pressure greater than (>) 180 millimeter of mercury (mmHg), diastolic >100 mmHg) Current history of chronic daily aspirin therapy (doses of =< 150 mg is permitted), bleeding disorders, and/or history of thromboembolic events Severe peripheral vascular disease or ulceration Unstable angina pectoris, or myocardial infarction within 6 months before start of study treatment, clinical significant abnormal electrocardiogram (ECG) at screening; In women of childbearing potential, pregnancy (absence to be confirmed by beta human chorionic gonadotropin [β HCG] test, unless a subject has previously undergone hysterectomy or bilateral ovariectomy), or lactation period Known alcohol or drug abuse Participation in another clinical trial within the past 30 days before start of study treatment All other significant diseases which, in the opinion of the principal investigator (PI), might impair the subject's tolerance of study treatment Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent Legal incapacity or limited legal capacity (not applicable only in rare cases) Known human immuno deficiency (HIV) infection and/or active hepatitis B or C virus infections Ongoing uncontrolled infections Contraindications to magnetic resonance imaging (MRI)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Responsible
Organizational Affiliation
Merck KGaA, Darmstadt, Germany
Official's Role
Study Director
Facility Information:
Facility Name
Christie Hospital
City
Manchester
Country
United Kingdom

12. IPD Sharing Statement

Learn more about this trial

EMD 525797 in Colorectal and Ovarian Cancer Patients With Liver Metastases

We'll reach out to this number within 24 hrs