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| ID | Type | Description | Link |
|---|---|---|---|
| 2008-001820-30 | EudraCT Number |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| EMD 525797 | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| EMD 525797 | Biological | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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. | 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. | 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. | Screening 1, screening 2, Week 1 Day 2, Week 1 Day 5, and Week 2 Day 1 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Responsible | Merck KGaA, Darmstadt, Germany | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Christie Hospital | Manchester | United Kingdom |
Enrolled: 61 screened for eligibility; 20 excluded (mainly non-fulfillment of inclusion or exclusion criteria), 41 participants were enrolled into the study.
First/last participant (informed consent): Feb2009/Sep 2013. Study completion date: 28 Nov 2013. The study was conducted at 2 centers in United Kingdom and Spain.
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| ID | Title | Description |
|---|---|---|
| FG000 | Abituzumab 250 mg | Abituzumab was administered as an intravenous infusion for an hour at a dose of 250 milligram (mg) at Weeks 1, 3 and 5. In case of clinical benefit (stable disease [SD], complete response [CR], or partial response [PR]) as assessed by the Response Evaluation Criteria in Solid Tumors version (RECIST) Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator. |
| FG001 | Abituzumab 500 mg | Abituzumab was administered as an intravenous infusion for an hour at a dose of 500 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator. |
| FG002 | Abituzumab 1000 mg | Abituzumab was administered as an intravenous infusion for an hour at a dose of 1000 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator. |
| FG003 | Abituzumab 1500 mg | Abituzumab was administered as an intravenous infusion for an hour at a dose of 1500 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
All subjects analysis set included all subjects who entered the trial (that is, all subjects who signed informed consent).
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Abituzumab 250 mg | Abituzumab was administered as an intravenous infusion for an hour at a dose of 250 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Dose escalation analysis set included all subjects in the safety analysis set who experienced any DLT during the DLT observation period, regardless of the number of investigational medicinal product (IMP) administrations and subjects who received the IMP at Weeks 1, 3, and 5 for Cohort 1 and at Weeks 1 and 3 for all other cohorts. | Posted | Number | Subjects | Up to Week 4 |
|
From the initiation of the trial treatment until 30 days after last administration of trial treatment.
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Abituzumab 250 mg | Abituzumab was administered as an intravenous infusion for an hour at a dose of 250 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Myocardial ischaemia | Cardiac disorders | MedDRA version 17.1 | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA version 17.1 | Non-systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Merck KGaA Communication Center | Merck Serono, a division of Merck KGaA | +49-6151-72-5200 | service@merckgroup.com |
Not provided
| ID | Term |
|---|---|
| C000592911 | Abituzumab |
Not provided
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|
| 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. | Screening 1, screening 2, Week 1 Day 2, Week 1 Day 5, and Week 2 Day 1 |
| 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. | 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. | 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. | 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. | 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) |
| BG001 | Abituzumab 500 mg | Abituzumab was administered as an intravenous infusion for an hour at a dose of 500 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator. |
| BG002 | Abituzumab 1000 mg | Abituzumab was administered as an intravenous infusion for an hour at a dose of 1000 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator. |
| BG003 | Abituzumab 1500 mg | Abituzumab was administered as an intravenous infusion for an hour at a dose of 1500 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator. |
| BG004 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| OG000 | Abituzumab 250 mg | Abituzumab was administered as an intravenous infusion for an hour at a dose of 250 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator. |
| OG001 | Abituzumab 500 mg | Abituzumab was administered as an intravenous infusion for an hour at a dose of 500 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator. |
| OG002 | Abituzumab 1000 mg | Abituzumab was administered as an intravenous infusion for an hour at a dose of 1000 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator. |
| OG003 | Abituzumab 1500 mg | Abituzumab was administered as an intravenous infusion for an hour at a dose of 1500 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator. |
|
|
| Primary | 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. | The DCE-MRI analysis set included all subjects who had at least one valid predose scan and at least one valid postdose (that is, after the infusion) scan. | Posted | Mean | Standard Deviation | min^-1 | Screening 1, screening 2, Week 1 Day 2, Week 1 Day 5, and Week 2 Day 1 |
|
|
|
| Secondary | 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. | The safety analysis set included all subjects who received at least one dose of IMP administration. | Posted | Number | Subjects | From the initiation of the trial treatment until 30 days after last administration of trial treatment. |
|
|
|
| Secondary | 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. | The full analysis set included all subjects who received at least one dose of IMP administration. "N" signifies the total number of participants evaluable for this outcome measure. Same subjects may be reported in more than one category. | Posted | Number | Subjects | Up to 4 years |
|
|
|
| Secondary | 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. | The safety analysis set included all subjects who received at least one dose of IMP administration. | Posted | Number | Subjects | Up to 4 weeks after last dose administration |
|
|
|
| Secondary | 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. | The immunogenicity analysis set included all subjects who received at least one dose of study drug administration and provided sufficient data from the antibodies samples. 'N' (number of subjects analyzed) signifies the subjects evaluable for this outcome measure. "n" signifies the number of subjects evaluable for each time point, respectively. | Posted | Number | Subjects | 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) |
|
|
|
| Primary | Blood Plasma Volume and Extravascular/Extracellular Volume | Blood plasma volume and extracellular/extravascular volume was measured using DCE-MRI. | The DCE-MRI analysis set included all subjects who had at least one valid predose scan and at least one valid postdose (that is, after the infusion) scan. | Posted | Mean | Standard Deviation | milliliter | Screening 1, screening 2, Week 1 Day 2, Week 1 Day 5, and Week 2 Day 1 |
|
|
|
| Primary | 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. | The DCE-MRI analysis set included all subjects who had at least one valid predose scan and at least one valid postdose (that is, after the infusion) scan. | Posted | Mean | Standard Deviation | (Millimoles/liter)*sec | Screening 1, screening 2, Week 1 Day 2, Week 1 Day 5, and Week 2 Day 1 |
|
|
|
| Primary | 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. | The DCE-MRI analysis set included all subjects who had at least one valid predose scan and at least one valid postdose (that is, after the infusion) scan. | Posted | Mean | Standard Deviation | Cubic millimeter (mm^3) | Screening 1, screening 2, Week 1 Day 2, Week 1 Day 5, and Week 2 Day 1 |
|
|
|
| Secondary | 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. | The safety analysis set included all subjects who received at least one dose of IMP administration. | Posted | Median | Full Range | months | 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) |
|
|
|
| 5 |
| 10 |
| 10 |
| 10 |
| EG001 | Abituzumab 500 mg | Abituzumab was administered as an intravenous infusion for an hour at a dose of 500 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator. | 7 | 13 | 13 | 13 |
| EG002 | Abituzumab 1000 mg | Abituzumab was administered as an intravenous infusion for an hour at a dose of 1000 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator. | 5 | 8 | 8 | 8 |
| EG003 | Abituzumab 1500 mg | Abituzumab was administered as an intravenous infusion for an hour at a dose of 1500 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator. | 7 | 10 | 10 | 10 |
| Abdominal pain | Gastrointestinal disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Ascites | Gastrointestinal disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Pyrexia | General disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Asthenia | General disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Disease progression | General disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Cholangitis | Hepatobiliary disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Hepatic failure | Hepatobiliary disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Drug hypersensitivity | Immune system disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Biliary tract infection | Infections and infestations | MedDRA version 17.1 | Non-systematic Assessment |
|
| International normalised ratio increased | Investigations | MedDRA version 17.1 | Non-systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Malignant ascites | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version 17.1 | Non-systematic Assessment |
|
| Haemorrhage intracranial | Nervous system disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Hemiparesis | Nervous system disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Hepatobiliary infection | Infections and infestations | MedDRA version 17.1 | Non-systematic Assessment |
|
| Hypochromic Anaemia | Blood and lymphatic system disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Lacrimation Increased | Eye disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Abdominal Distension | Gastrointestinal disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Abdominal Pain | Gastrointestinal disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Anal haemorrhage | Gastrointestinal disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Ascites | Gastrointestinal disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Dysphagia | Gastrointestinal disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Flatulence | Gastrointestinal disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Asthenia' | General disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Early Satiety | General disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Fatigue | General disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Influenza like illness | General disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Localised oedema | General disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Oedema | General disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| oedema peripheral | General disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Pain | General disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Pyrexia | General disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Hepatic function abnormal | Hepatobiliary disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Hepatic pain | Hepatobiliary disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Hepatomegaly | Hepatobiliary disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Drug hypersensitivity | Immune system disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Bacterial vaginosis | Infections and infestations | MedDRA version 17.1 | Non-systematic Assessment |
|
| Infection | Infections and infestations | MedDRA version 17.1 | Non-systematic Assessment |
|
| Lower respiratory tract infection | Infections and infestations | MedDRA version 17.1 | Non-systematic Assessment |
|
| Oral Candidiasis | Infections and infestations | MedDRA version 17.1 | Non-systematic Assessment |
|
| Oral Herpes | Infections and infestations | MedDRA version 17.1 | Non-systematic Assessment |
|
| Respiratory tract infection | Infections and infestations | MedDRA version 17.1 | Non-systematic Assessment |
|
| Rhinitis | Infections and infestations | MedDRA version 17.1 | Non-systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA version 17.1 | Non-systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA version 17.1 | Non-systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | MedDRA version 17.1 | Non-systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA version 17.1 | Non-systematic Assessment |
|
| Blood alkaline phosphatase increased | Investigations | MedDRA version 17.1 | Non-systematic Assessment |
|
| Blood bilirubin increased | Investigations | MedDRA version 17.1 | Non-systematic Assessment |
|
| Blood cholesterol increased | Investigations | MedDRA version 17.1 | Non-systematic Assessment |
|
| Blood creatinine increased | Investigations | MedDRA version 17.1 | Non-systematic Assessment |
|
| Blood potassium increased | Investigations | MedDRA version 17.1 | Non-systematic Assessment |
|
| Electrocardiogram Qt prolonged | Investigations | MedDRA version 17.1 | Non-systematic Assessment |
|
| Eosinophil count increased | Investigations | MedDRA version 17.1 | Non-systematic Assessment |
|
| Haemoglobin decreased | Investigations | MedDRA version 17.1 | Non-systematic Assessment |
|
| International normalised ratio increased | Investigations | MedDRA version 17.1 | Non-systematic Assessment |
|
| Platelet count decreased | Investigations | MedDRA version 17.1 | Non-systematic Assessment |
|
| Cachexia | Metabolism and nutrition disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Peritumoural oedema | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version 17.1 | Non-systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Lethargy | Nervous system disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Bladder Spasm | Renal and urinary disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Dysuria | Renal and urinary disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Polyuria | Renal and urinary disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Proteinuria | Renal and urinary disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Pelvic pain | Reproductive system and breast disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Vulvovaginal pruritus | Reproductive system and breast disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Hiccups | Respiratory, thoracic and mediastinal disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Pulmonary haemorrhage | Respiratory, thoracic and mediastinal disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Dermatitis alergic | Skin and subcutaneous tissue disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Eczema | Skin and subcutaneous tissue disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Night sweats | Skin and subcutaneous tissue disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Pruritus generalised | Skin and subcutaneous tissue disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Rash erythematous | Skin and subcutaneous tissue disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Rash macular | Skin and subcutaneous tissue disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Rash pruritic | Skin and subcutaneous tissue disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Flushing | Vascular disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Hot flush | Vascular disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA version 17.1 | Non-systematic Assessment |
|
Not provided
| Screening 2 |
|
| Week 1 Day 2 |
|
| Week 1 Day 5 |
|
| Week 2 Day 1 |
|
| Serious TEAEs |
|
| TEAEs leading to Discontinuation |
|
| TEAEs Leading to Death |
|
| PR |
|
| SD |
|
| Progressive Disease |
|
| Not Assessable |
|
| Tumor Response |
|
| Clinical Benefit |
|
| Week 3 Day 1 (n=9,11,7,7) |
|
| Week 5 Day 1 (n=6,9,6,2) |
|
| Week 6 Day 1 (n=0,6,5,2) |
|
| Week 7 Day 1 (n=0,5,5,2) |
|
| Week 8 Day 1 (n=4,0,0,0) |
|
| Week 11 (n=0,1,3,0) |
|
| EOS Visit (n=6,3,2,1) |
|
| Blood Plasma Volume: Screening 2 |
|
| Blood Plasma Volume: Week 1 Day 2 |
|
| Blood Plasma Volume: Week 1 Day 5 |
|
| Blood Plasma Volume: Week 2 Day 1 |
|
| Extravascular Volume: Screening 1 |
|
| Extravascular Volume: Screening 2 |
|
| Extravascular Volume: Week 1 Day 2 |
|
| Extravascular Volume: Week 1 Day 5 |
|
| Extravascular Volume: Week 2 Day 1 |
|
| Screening 2 |
|
| Week 1 Day 2 |
|
| Week 1 Day 5 |
|
| Week 2 Day 1 |
|
| Whole tumor volume: Screening 2 |
|
| Whole tumor volume: Week 1 Day 2 |
|
| Whole tumor volume: Week 1 Day 5 |
|
| Whole tumor volume: Week 2 Day 1 |
|
| EnhancingTumor Volume: Screening 1 |
|
| Enhancing tumor volume: Screening 2 |
|
| Enhancing tumor volume: Week 1 Day 2 |
|
| Enhancing tumor volume: Week 1 Day 5 |
|
| Enhancing tumor volume: Week 2 Day 1 |
|