Colorectal and Ovarian Cancer Patients With Liver MetastasesPhase 1NCT00848510
EMD 525797 in Colorectal and Ovarian Cancer Patients With Liver Metastases
A Phase 1 study testing EMD 525797 in people with Colorectal and Ovarian Cancer Patients With Liver Metastases, run by Merck KGaA, Darmstadt, Germany at 1 site in United Kingdom.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal and Ovarian Cancer Patients With Liver Metastases
- What is being tested?
- EMD 525797
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Feb 2009to Nov 2013
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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.
Who cannot join
- 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
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- 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)
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
- Being tested
- EMD 525797
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EMD 525797Biological
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.
| Study group | Role | What they receive |
|---|---|---|
| EMD 525797 | Experimental | Not described Receives: Biological: EMD 525797 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to Week 4
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.
Measured: Screening 1, screening 2, Week 1 Day 2, Week 1 Day 5, and Week 2 Day 1
Blood Plasma Volume and Extravascular/Extracellular Volume
Blood plasma volume and extracellular/extravascular volume was measured using DCE-MRI.
Measured: Screening 1, screening 2, Week 1 Day 2, Week 1 Day 5, and Week 2 Day 1
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.
Measured: Screening 1, screening 2, Week 1 Day 2, Week 1 Day 5, and Week 2 Day 1
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.
Measured: Screening 1, screening 2, Week 1 Day 2, Week 1 Day 5, and Week 2 Day 1
Secondary outcomes (5)
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.
Measured: From the initiation of the trial treatment until 30 days after last administration of trial treatment.
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.
Measured: Up to 4 years
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.
Measured: Up to 4 weeks after last dose administration
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.
Measured: 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)
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.
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Feb 2009 (estimated)
- Study startFeb 2009
- Primary completionNov 2013
- Study completionNov 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Colorectal and Ovarian Cancer Patients With Liver MetastasesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck KGaA, Darmstadt, Germany
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Responsible, Study director, Merck KGaA, Darmstadt, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00848510
- Sponsor's protocol ID
- EMR 62242-003
- Other IDs
- 2008-001820-30, 2008
- Status last verified
- Nov 2015
- First submitted
- 19 Feb 2009
- Last updated
- 14 Dec 2015
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 14 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00848510
- Acronym / sponsor ID
- EMR 62242-003
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- Merck KGaA, Darmstadt, GermanyIndustry (pharma, biotech, devices)
- Study start
- Feb 2009
- Primary completion
- Nov 2013 (actual)
- Study completion
- Nov 2013 (actual)
- First posted
- 20 Feb 2009 (estimated)
- Results
- Posted 14 Dec 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| EMD 525797 | Experimental | Biological: EMD 525797 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (20 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EMD 525797Abituzumab 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. | Biological | EMD 525797 |
Primary outcome
Number of Subjects With Dose Limiting Toxicities (DLTs)
Time frame: Up to Week 4
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
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
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
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
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.
5 secondary outcomes
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.
Number of Subjects With Best Overall Response, Tumor Response and Clinical Benefit
Time frame: Up to 4 years
Number of Subjects With Worsened Post Baseline Shift in ECOG Performance Status Score
Time frame: Up to 4 weeks after last dose administration
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)
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)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Dec 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Responsible study director
Merck KGaA, Darmstadt, Germany
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing EMD 525797 in people with Colorectal and Ovarian Cancer Patients With Liver Metastases, run by Merck KGaA, Darmstadt, Germany at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Dec 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Dec 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Subjects With Dose Limiting Toxicities (DLTs) (time frame: Up to Week 4). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Dec 2015.