Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

EMD 525797 in Colorectal and Ovarian Cancer Patients With Liver Metastases

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck KGaA
ClinicalTrials.gov Identifier:
NCT00848510
First received: February 19, 2009
Last updated: November 9, 2015
Last verified: November 2015
  Purpose

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.


Condition Intervention Phase
Colorectal and Ovarian Cancer Patients With Liver Metastases
Biological: EMD 525797
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Merck KGaA:

Primary Outcome Measures:
  • Number of Subjects With Dose Limiting Toxicities (DLTs) [ Time Frame: Up to Week 4 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Screening 1, screening 2, Week 1 Day 2, Week 1 Day 5, and Week 2 Day 1 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Screening 1, screening 2, Week 1 Day 2, Week 1 Day 5, and Week 2 Day 1 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Screening 1, screening 2, Week 1 Day 2, Week 1 Day 5, and Week 2 Day 1 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Screening 1, screening 2, Week 1 Day 2, Week 1 Day 5, and Week 2 Day 1 ] [ Designated as safety issue: No ]
    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 [ Time Frame: From the initiation of the trial treatment until 30 days after last administration of trial treatment. ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to 4 weeks after last dose administration ] [ Designated as safety issue: No ]
    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 [ 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) ] [ Designated as safety issue: No ]
    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 [ 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) ] [ Designated as safety issue: No ]
    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.


Enrollment: 41
Study Start Date: February 2009
Study Completion Date: November 2013
Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: EMD 525797 Biological: EMD 525797
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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  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: NCT00848510

Locations
United Kingdom
Christie Hospital
Manchester, United Kingdom
Sponsors and Collaborators
Merck KGaA
Investigators
Study Director: Medical Responsible Merck KGaA
  More Information

Responsible Party: Merck KGaA
ClinicalTrials.gov Identifier: NCT00848510     History of Changes
Other Study ID Numbers: EMR 62242-003  2008-001820-30 
Study First Received: February 19, 2009
Results First Received: July 24, 2015
Last Updated: November 9, 2015
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: National Health Service
United Kingdom: Research Ethics Committee
United States: Food and Drug Administration
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Spain: Comité Ético de Investigación Clínica
Spain: Departament de Salut de la Generalitat de Catalunya
Spain: Ethics Committee
Spain: Ministerio de Sanidad, Servicios Sociales e Igualdad
Spain: Ministry of Health
Spain: Ministry of Health and Consumption
Spain: Spanish Agency of Medicines
Spain: CEIC Puerta hierro

Additional relevant MeSH terms:
Neoplasm Metastasis
Ovarian Neoplasms
Liver Neoplasms
Neoplastic Processes
Neoplasms
Pathologic Processes
Endocrine Gland Neoplasms
Neoplasms by Site
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Digestive System Neoplasms
Digestive System Diseases
Liver Diseases

ClinicalTrials.gov processed this record on December 02, 2016