Aflibercept Compared to Placebo in Term of Efficacy in Pa... | NCT00574275

ID	Type	Description	Link
EudraCT 2007-003476-19

Name	Class
Regeneron Pharmaceuticals	INDUSTRY

Description Module

Label	Type	Description	Intervention Names
Placebo and Gemcitabine	Placebo Comparator	Participants with metastatic pancreatic cancer administered Placebo and 1000 mg/m^2 Gemcitabine.	Drug: Placebo Drug: Gemcitabine
Aflibercept and Gemcitabine	Experimental	Participants with metastatic pancreatic cancer administered 4 mg/kg Aflibercept and 1000 mg/m^2 Gemcitabine.	Drug: Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®) Drug: Gemcitabine

Name	Type	Description	Arm Group Labels	Other Names
Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®)	Drug	4 mg/kg was administered intravenously (IV) over 1 hour once every 2 weeks, on Days 1 and 15 of each 28-day cycle.

Measure	Description	Time Frame
Overall Survival (OS)	OS is the time interval from the date of randomization to the date of death due to any cause. If death was not observed during the study, data on OS were censored at the earlier of the last date participant was known to be alive, or the study data cutoff date (11 September 2009). OS time was estimated from Kaplan-Meier Plots.	From the first randomization until the end of study data cutoff date (approximately 2 years)

Measure	Description	Time Frame
Progression Free Survival (PFS) Based on Response Evaluation Criteria in Solid Tumors [RECIST] Criteria	PFS was the time interval from the date of registration to the date of progression, or death from any cause if it occurs before tumor progression is documented. Tumor progression was assessed using RECIST criteria, by which progression was a pre-defined increase in the size of existing tumors or appearance of one or more new tumors. If a participant did not progress or die, the progression was censored to the date of the last valid tumor assessment or data cut-off, whichever was earlier. Median PFS time was estimated from Kaplan-Meier Plots.

Name	Affiliation	Role
Clinical Sciences & Operations	Sanofi	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Sanofi-Aventis Administrative Office		Bridgewater	New Jersey	08807	United States
Sanofi-Aventis Administrative Office

PubMed Identifier	Type	Citation	Retractions
23642329	Result	Rougier P, Riess H, Manges R, Karasek P, Humblet Y, Barone C, Santoro A, Assadourian S, Hatteville L, Philip PA. Randomised, placebo-controlled, double-blind, parallel-group phase III study evaluating aflibercept in patients receiving first-line treatment with gemcitabine for metastatic pancreatic cancer. Eur J Cancer. 2013 Aug;49(12):2633-42. doi: 10.1016/j.ejca.2013.04.002. Epub 2013 Apr 30.

ID	Title	Description
FG000	Placebo and Gemcitabine	Placebo: 4 mg/kg was administered IV over 1 hour once every 2 weeks, on Days 1 and 15 of each 28-day cycle. Gemcitabine: 1000 mg/m^2 administered IV over 30 minutes on Days 1, 8, 15, and 22 of Cycle 1 (28 days), and then Days 1, 8, and 15 of subsequent 28-day cycles.
FG001

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

Overall Survival (OS)

OS is the time interval from the date of randomization to the date of death due to any cause. If death was not observed during the study, data on OS were censored at the earlier of the last date participant was known to be alive, or the study data cutoff date (11 September 2009).

OS time was estimated from Kaplan-Meier Plots.

Intent-to-treat (ITT) population, which included all randomized participants.

Posted

Median

95% Confidence Interval

months

From the first randomization until the end of study data cutoff date (approximately 2 years)

OS Event (Death)

Participants

ID	Title	Description
OG000	Placebo and Gemcitabine	Placebo: 4 mg/kg was administered IV over 1 hour once every 2 weeks, on Days 1 and 15 of each 28-day cycle. Gemcitabine: 1000 mg/m^2 administered IV over 30 minutes on Days 1, 8, 15, and 22 of Cycle 1 (28 days), and then Days 1, 8, and 15 of subsequent 28-day cycles.
OG001	Aflibercept and Gemcitabine	Aflibercept: 4 mg/kg was administered IV over 1 hour once every 2 weeks, on Days 1 and 15 of each 28-day cycle. Gemcitabine: 1000 mg/m^2 administered IV over 30 minutes on Days 1, 8, 15, and 22 of Cycle 1 (28 days), and then Days 1, 8, and 15 of subsequent 28-day cycles.

Units	Counts
Participants	OG000275 OG001271
OS Event (Death)	OG000142 OG001

Title

Denominators

Categories

Title	Measurements
	OG0007.75(6.768 to 8.575) OG0016.54(5.552 to 7.852)

Secondary

Progression Free Survival (PFS) Based on Response Evaluation Criteria in Solid Tumors [RECIST] Criteria

PFS was the time interval from the date of registration to the date of progression, or death from any cause if it occurs before tumor progression is documented. Tumor progression was assessed using RECIST criteria, by which progression was a pre-defined increase in the size of existing tumors or appearance of one or more new tumors.

If a participant did not progress or die, the progression was censored to the date of the last valid tumor assessment or data cut-off, whichever was earlier.

Median PFS time was estimated from Kaplan-Meier Plots.

Intent-to-treat (ITT) population, which included all randomized participants.

Posted

Median

95% Confidence Interval

months

From the first randomization until the end of study data cutoff date (approximately 2 years)

PFS Events

Participants

ID	Title	Description
OG000	Placebo and Gemcitabine	Placebo: 4 mg/kg was administered IV over 1 hour once every 2 weeks, on Days 1 and 15 of each 28-day cycle. Gemcitabine: 1000 mg/m^2 administered IV over 30 minutes on Days 1, 8, 15, and 22 of Cycle 1 (28 days), and then Days 1, 8, and 15 of subsequent 28-day cycles.
OG001	Aflibercept and Gemcitabine	Aflibercept: 4 mg/kg was administered IV over 1 hour once every 2 weeks, on Days 1 and 15 of each 28-day cycle. Gemcitabine: 1000 mg/m^2 administered IV over 30 minutes on Days 1, 8, 15, and 22 of Cycle 1 (28 days), and then Days 1, 8, and 15 of subsequent 28-day cycles.

Secondary

Objective Response Rate (ORR) Assessed by the Investigators According to RECIST Criteria

Objective response (OR) included complete response [CR] and partial response [PR]. OR was to be assessed by the Investigators according to RECIST criteria, and confirmed by repeating tumor imaging at least 4 weeks after the first radiological documentation of response.

CR would reflect the disappearance of all tumor lesions and PR would reflect a defined reduction of tumor burden.

However, OR analysis was not performed, as the study was terminated due to futility.

Since the study was terminated due to futility, this analysis was not performed.

Posted

From the first randomization until the end of the study data cutoff date (approximately 2 years)

ID	Title	Description
OG000	Placebo and Gemcitabine	Placebo: 4 mg/kg was administered IV over 1 hour once every 2 weeks, on Days 1 and 15 of each 28-day cycle. Gemcitabine: 1000 mg/m^2 administered IV over 30 minutes on Days 1, 8, 15, and 22 of Cycle 1 (28 days), and then Days 1, 8, and 15 of subsequent 28-day cycles.
OG001	Aflibercept and Gemcitabine	Aflibercept: 4 mg/kg was administered IV over 1 hour once every 2 weeks, on Days 1 and 15 of each 28-day cycle. Gemcitabine: 1000 mg/m^2 administered IV over 30 minutes on Days 1, 8, 15, and 22 of Cycle 1 (28 days), and then Days 1, 8, and 15 of subsequent 28-day cycles.

Secondary

Clinical Benefit

Clinical benefit was to be assessed in all participants by time to symptom worsening (TTSW), evaluated from the time of randomization to symptom worsening, as well as by improvement in tumor related symptoms.

However, this analysis was not performed, as the study was terminated due to futility.

Since the study was terminated due to futility, analysis for this endpoint was not performed.

Posted

From the first randomization until the end of the study data cutoff date (approximately 2 years)

ID	Title	Description
OG000	Placebo and Gemcitabine	Placebo: 4 mg/kg was administered IV over 1 hour once every 2 weeks, on Days 1 and 15 of each 28-day cycle. Gemcitabine: 1000 mg/m^2 administered IV over 30 minutes on Days 1, 8, 15, and 22 of Cycle 1 (28 days), and then Days 1, 8, and 15 of subsequent 28-day cycles.
OG001	Aflibercept and Gemcitabine	Aflibercept: 4 mg/kg was administered IV over 1 hour once every 2 weeks, on Days 1 and 15 of each 28-day cycle. Gemcitabine: 1000 mg/m^2 administered IV over 30 minutes on Days 1, 8, 15, and 22 of Cycle 1 (28 days), and then Days 1, 8, and 15 of subsequent 28-day cycles.

Units	Counts

Secondary

Safety-Number of Participants With Adverse Events (AE)

All AEs regardless of seriousness or relationship to study treatment, spanning from the signature of informed consent until 30 days after the last administration of study treatment, were recorded. The number of participants with all treatment emergent adverse events (TEAE), serious adverse events (SAE), TEAE leading to death, and TEAE leading to permanent treatment discontinuation are reported.

The safety population included all randomized participants who were administered at least 1 dose of study medications (placebo, aflibercept, or gemcitabine). For safety analyses, participants were analyzed according to the treatment received.

Posted

Number

participants

up to 30 days after treatment discontinuation. SAEs and related AEs were followed till resolved or stabilized.

ID	Title	Description
OG000	Placebo and Gemcitabine	Placebo: 4 mg/kg was administered IV over 1 hour once every 2 weeks, on Days 1 and 15 of each 28-day cycle. Gemcitabine: 1000 mg/m^2 administered IV over 30 minutes on Days 1, 8, 15, and 22 of Cycle 1 (28 days), and then Days 1, 8, and 15 of subsequent 28-day cycles.
OG001	Aflibercept and Gemcitabine	Aflibercept: 4 mg/kg was administered IV over 1 hour once every 2 weeks, on Days 1 and 15 of each 28-day cycle. Gemcitabine: 1000 mg/m^2 administered IV over 30 minutes on Days 1, 8, 15, and 22 of Cycle 1 (28 days), and then Days 1, 8, and 15 of subsequent 28-day cycles.

Secondary

Number of Participants With Anti-drug Antibodies

Anti-drug antibodies in the participants blood sample were detected using a validated immunoassay. The validated lower limit of detection (LLOD) for the assay was about 5.4 ng/mL in the absence of aflibercept and about 25.2 ng/mL in the presence of 20 μg/mL of aflibercept.

Safety population with samples available for analysis

Posted

Number

participants

Up to 90 days post last dose of study drug

ID	Title	Description
OG000	Placebo and Gemcitabine	Placebo: 4 mg/kg was administered IV over 1 hour once every 2 weeks, on Days 1 and 15 of each 28-day cycle. Gemcitabine: 1000 mg/m^2 administered IV over 30 minutes on Days 1, 8, 15, and 22 of Cycle 1 (28 days), and then Days 1, 8, and 15 of subsequent 28-day cycles.
OG001	Aflibercept and Gemcitabine	Aflibercept: 4 mg/kg was administered IV over 1 hour once every 2 weeks, on Days 1 and 15 of each 28-day cycle. Gemcitabine: 1000 mg/m^2 administered IV over 30 minutes on Days 1, 8, 15, and 22 of Cycle 1 (28 days), and then Days 1, 8, and 15 of subsequent 28-day cycles.

Units	Counts
Participants

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Urinary tract infection	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0003 affected271 at risk EG0010 affected270 at risk
Pneumonia	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0003 affected271 at risk EG0012 affected270 at risk
Pharyngitis	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Influenza	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Sepsis	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0002 affected271 at risk EG0012 affected270 at risk
Abdominal abscess	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0001 affected271 at risk EG0011 affected270 at risk
Bronchopneumonia	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Bacterascites	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0012 affected270 at risk
Escherichia urinary tract infection	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Skin infection	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Cellulitis	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0001 affected271 at risk EG0010 affected270 at risk
Device related infection	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0003 affected271 at risk EG0010 affected270 at risk
Biliary sepsis	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0002 affected271 at risk EG0011 affected270 at risk
Clostridium difficile colitis	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Enterocolitis infectious	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Febrile infection	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Liver abscess	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Peritoneal infection	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Subdiaphragmatic abscess	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Escherichia sepsis	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0002 affected271 at risk EG0010 affected270 at risk
Anal abscess	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0001 affected271 at risk EG0010 affected270 at risk
Cholecystitis infective	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0001 affected271 at risk EG0010 affected270 at risk
Fungal oesophagitis	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0001 affected271 at risk EG0010 affected270 at risk
Pyelonephritis	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0001 affected271 at risk EG0010 affected270 at risk
Urosepsis	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0001 affected271 at risk EG0010 affected270 at risk
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.1	Systematic Assessment	EG0002 affected271 at risk EG0011 affected270 at risk
Cancer pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.1	Systematic Assessment	EG0001 affected271 at risk EG0012 affected270 at risk
Malignant ascites	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.1	Systematic Assessment	EG0002 affected271 at risk EG0010 affected270 at risk
Bladder neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Tumour associated fever	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.1	Systematic Assessment	EG0002 affected271 at risk EG0010 affected270 at risk
Paraneoplastic syndrome	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.1	Systematic Assessment	EG0001 affected271 at risk EG0010 affected270 at risk
Tumour haemorrhage	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.1	Systematic Assessment	EG0001 affected271 at risk EG0010 affected270 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0012 affected270 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected271 at risk EG0012 affected270 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA 13.1	Systematic Assessment	EG0002 affected271 at risk EG0014 affected270 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected271 at risk EG0011 affected270 at risk
Splenic vein thrombosis	Blood and lymphatic system disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected271 at risk EG0011 affected270 at risk
Anaemia of malignant disease	Blood and lymphatic system disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected271 at risk EG0011 affected270 at risk
Splenic infarction	Blood and lymphatic system disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected271 at risk EG0010 affected270 at risk
Disseminated intravascular coagulation	Blood and lymphatic system disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected271 at risk EG0010 affected270 at risk
Inappropriate antidiuretic hormone secretion	Endocrine disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 13.1	Systematic Assessment	EG0002 affected271 at risk EG0011 affected270 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 13.1	Systematic Assessment	EG0005 affected271 at risk EG0015 affected270 at risk
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected271 at risk EG0011 affected270 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Failure to thrive	Metabolism and nutrition disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 13.1	Systematic Assessment	EG0002 affected271 at risk EG0010 affected270 at risk
Confusional state	Psychiatric disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0012 affected270 at risk
Completed suicide	Psychiatric disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Mental status changes	Psychiatric disorders	MedDRA 13.1	Systematic Assessment	EG0002 affected271 at risk EG0010 affected270 at risk
Syncope	Nervous system disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Ischaemic stroke	Nervous system disorders	MedDRA 13.1	Systematic Assessment	EG0002 affected271 at risk EG0011 affected270 at risk
Cerebellar syndrome	Nervous system disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Cerebral haemorrhage	Nervous system disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Cerebral infarction	Nervous system disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Diabetic ketoacidotic hyperglycaemic coma	Nervous system disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Convulsion	Nervous system disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected271 at risk EG0010 affected270 at risk
Hepatic encephalopathy	Nervous system disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected271 at risk EG0010 affected270 at risk
Intracranial pressure increased	Nervous system disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected271 at risk EG0010 affected270 at risk
Monoplegia	Nervous system disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected271 at risk EG0010 affected270 at risk
Spinal cord compression	Nervous system disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected271 at risk EG0010 affected270 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0012 affected270 at risk
Cardiac failure	Cardiac disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0012 affected270 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected271 at risk EG0011 affected270 at risk
Atrial flutter	Cardiac disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Extrasystoles	Cardiac disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Left ventricular failure	Cardiac disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Myocardial ischaemia	Cardiac disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Ventricular extrasystoles	Cardiac disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected271 at risk EG0010 affected270 at risk
Sinus bradycardia	Cardiac disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected271 at risk EG0010 affected270 at risk
Ventricular fibrillation	Cardiac disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected271 at risk EG0010 affected270 at risk
Hypertension	Vascular disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0014 affected270 at risk
Deep vein thrombosis	Vascular disorders	MedDRA 13.1	Systematic Assessment	EG0002 affected271 at risk EG0013 affected270 at risk
Thrombophlebitis superficial	Vascular disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected271 at risk EG0011 affected270 at risk
Jugular vein thrombosis	Vascular disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Hypertensive crisis	Vascular disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0012 affected270 at risk
Embolism arterial	Vascular disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0012 affected270 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Systematic Assessment	EG0003 affected271 at risk EG0012 affected270 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Systematic Assessment	EG00011 affected271 at risk EG0014 affected270 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0012 affected270 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Interstitial lung disease	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Systematic Assessment	EG0002 affected271 at risk EG0011 affected270 at risk
Pneumonia aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected271 at risk EG0011 affected270 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Tachypnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected271 at risk EG0010 affected270 at risk
Pleuritic pain	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected271 at risk EG0010 affected270 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected271 at risk EG0010 affected270 at risk
Nausea	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0003 affected271 at risk EG0013 affected270 at risk
Vomiting	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0006 affected271 at risk EG00110 affected270 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0002 affected271 at risk EG0011 affected270 at risk
Constipation	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected271 at risk EG0010 affected270 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG00011 affected271 at risk EG0016 affected270 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0012 affected270 at risk
Ascites	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0002 affected271 at risk EG0014 affected270 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected271 at risk EG0011 affected270 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0004 affected271 at risk EG0014 affected270 at risk
Dysphagia	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected271 at risk EG0010 affected270 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected271 at risk EG0014 affected270 at risk
Haematemesis	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected271 at risk EG0010 affected270 at risk
Duodenal obstruction	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected271 at risk EG0013 affected270 at risk
Duodenal stenosis	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected271 at risk EG0013 affected270 at risk
Gastrointestinal obstruction	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected271 at risk EG0011 affected270 at risk
Melaena	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0012 affected270 at risk
Ileus	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0003 affected271 at risk EG0011 affected270 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected271 at risk EG0011 affected270 at risk
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Duodenal ulcer haemorrhage	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Enteritis	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Enterocutaneous fistula	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Gastric ulcer haemorrhage	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Ileus paralytic	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Intestinal perforation	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Oesophageal stenosis	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Pancreatitis chronic	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Peritonitis	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Colonic obstruction	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected271 at risk EG0010 affected270 at risk
Gastrointestinal ischaemia	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected271 at risk EG0010 affected270 at risk
Gastrointestinal oedema	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected271 at risk EG0010 affected270 at risk
Oesophagitis haemorrhagic	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected271 at risk EG0010 affected270 at risk
Pancreatitis	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected271 at risk EG0010 affected270 at risk
Thrombosis mesenteric vessel	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected271 at risk EG0010 affected270 at risk
Jaundice	Hepatobiliary disorders	MedDRA 13.1	Systematic Assessment	EG0002 affected271 at risk EG0013 affected270 at risk
Hyperbilirubinaemia	Hepatobiliary disorders	MedDRA 13.1	Systematic Assessment	EG0002 affected271 at risk EG0013 affected270 at risk
Cholangitis	Hepatobiliary disorders	MedDRA 13.1	Systematic Assessment	EG0004 affected271 at risk EG0015 affected270 at risk
Bile duct obstruction	Hepatobiliary disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected271 at risk EG0012 affected270 at risk
Bile duct stenosis	Hepatobiliary disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0012 affected270 at risk
Portal vein thrombosis	Hepatobiliary disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0012 affected270 at risk
Cholangitis acute	Hepatobiliary disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected271 at risk EG0011 affected270 at risk
Cholecystitis acute	Hepatobiliary disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Jaundice cholestatic	Hepatobiliary disorders	MedDRA 13.1	Systematic Assessment	EG0002 affected271 at risk EG0010 affected270 at risk
Hepatic failure	Hepatobiliary disorders	MedDRA 13.1	Systematic Assessment	EG0002 affected271 at risk EG0010 affected270 at risk
Portal hypertension	Hepatobiliary disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected271 at risk EG0010 affected270 at risk
Dermatitis	Skin and subcutaneous tissue disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Urticaria	Skin and subcutaneous tissue disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Skin ulcer	Skin and subcutaneous tissue disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected271 at risk EG0010 affected270 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Groin pain	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Myositis	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Systematic Assessment	EG0002 affected271 at risk EG0010 affected270 at risk
Proteinuria	Renal and urinary disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Haematuria	Renal and urinary disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Nephrotic syndrome	Renal and urinary disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0012 affected270 at risk
Renal failure	Renal and urinary disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Renal failure acute	Renal and urinary disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected271 at risk EG0011 affected270 at risk
Epididymitis	Reproductive system and breast disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Fatigue	General disorders	MedDRA 13.1	Systematic Assessment	EG0005 affected271 at risk EG0011 affected270 at risk
Pyrexia	General disorders	MedDRA 13.1	Systematic Assessment	EG0005 affected271 at risk EG0013 affected270 at risk
Asthenia	General disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected271 at risk EG0013 affected270 at risk
Disease progression	General disorders	MedDRA 13.1	Systematic Assessment	EG00025 affected271 at risk EG00138 affected270 at risk
Pain	General disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected271 at risk EG0010 affected270 at risk
Device occlusion	General disorders	MedDRA 13.1	Systematic Assessment	EG0002 affected271 at risk EG0013 affected270 at risk
Performance status decreased	General disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Malaise	General disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Non-cardiac chest pain	General disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected271 at risk EG0011 affected270 at risk
Device dislocation	General disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Sudden death	General disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Death	General disorders	MedDRA 13.1	Systematic Assessment	EG0004 affected271 at risk EG0010 affected270 at risk
Weight decreased	Investigations	MedDRA 13.1	Systematic Assessment	EG0001 affected271 at risk EG0010 affected270 at risk
Hepatic enzyme increased	Investigations	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Ejection fraction decreased	Investigations	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Blood glucose fluctuation	Investigations	MedDRA 13.1	Systematic Assessment	EG0001 affected271 at risk EG0010 affected270 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA 13.1	Systematic Assessment	EG0001 affected271 at risk EG0010 affected270 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Anastomotic leak	Injury, poisoning and procedural complications	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Hip fracture	Injury, poisoning and procedural complications	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk
Therapeutic agent toxicity	Injury, poisoning and procedural complications	MedDRA 13.1	Systematic Assessment	EG0000 affected271 at risk EG0011 affected270 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Urinary tract infection	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG00017 affected271 at risk EG00116 affected270 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 13.1	Systematic Assessment	EG00071 affected271 at risk EG00185 affected270 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 13.1	Systematic Assessment	EG00017 affected271 at risk EG00147 affected270 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 13.1	Systematic Assessment	EG00072 affected271 at risk EG00178 affected270 at risk
Insomnia	Psychiatric disorders	MedDRA 13.1	Systematic Assessment	EG00018 affected271 at risk EG00128 affected270 at risk
Depression	Psychiatric disorders	MedDRA 13.1	Systematic Assessment	EG0008 affected271 at risk EG00119 affected270 at risk
Anxiety	Psychiatric disorders	MedDRA 13.1	Systematic Assessment	EG00013 affected271 at risk EG00116 affected270 at risk
Headache	Nervous system disorders	MedDRA 13.1	Systematic Assessment	EG00019 affected271 at risk EG00151 affected270 at risk
Dysgeusia	Nervous system disorders	MedDRA 13.1	Systematic Assessment	EG0008 affected271 at risk EG00115 affected270 at risk
Hypertension	Vascular disorders	MedDRA 13.1	Systematic Assessment	EG00017 affected271 at risk EG00196 affected270 at risk
Deep vein thrombosis	Vascular disorders	MedDRA 13.1	Systematic Assessment	EG00016 affected271 at risk EG0019 affected270 at risk
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Systematic Assessment	EG0006 affected271 at risk EG00140 affected270 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Systematic Assessment	EG0005 affected271 at risk EG00137 affected270 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Systematic Assessment	EG00016 affected271 at risk EG00126 affected270 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Systematic Assessment	EG00014 affected271 at risk EG00114 affected270 at risk
Nausea	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG000124 affected271 at risk EG001102 affected270 at risk
Vomiting	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG00077 affected271 at risk EG00182 affected270 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG00057 affected271 at risk EG00165 affected270 at risk
Constipation	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG00073 affected271 at risk EG00164 affected270 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG00061 affected271 at risk EG00154 affected270 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG00016 affected271 at risk EG00143 affected270 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG00028 affected271 at risk EG00133 affected270 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 13.1	Systematic Assessment	EG00019 affected271 at risk EG00117 affected270 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Systematic Assessment	EG00023 affected271 at risk EG00127 affected270 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Systematic Assessment	EG00010 affected271 at risk EG00115 affected270 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Systematic Assessment	EG0004 affected271 at risk EG00114 affected270 at risk
Proteinuria	Renal and urinary disorders	MedDRA 13.1	Systematic Assessment	EG0006 affected271 at risk EG00130 affected270 at risk
Fatigue	General disorders	MedDRA 13.1	Systematic Assessment	EG000103 affected271 at risk EG00197 affected270 at risk
Pyrexia	General disorders	MedDRA 13.1	Systematic Assessment	EG00047 affected271 at risk EG00151 affected270 at risk
Asthenia	General disorders	MedDRA 13.1	Systematic Assessment	EG00042 affected271 at risk EG00151 affected270 at risk
Oedema peripheral	General disorders	MedDRA 13.1	Systematic Assessment	EG00043 affected271 at risk EG00133 affected270 at risk
Weight decreased	Investigations	MedDRA 13.1	Systematic Assessment	EG00043 affected271 at risk EG00181 affected270 at risk

ID	Title	Description
BG000	Placebo/Gemcitabine	Placebo: 4 mg/kg was administered IV over 1 hour once every 2 weeks, on Days 1 and 15 of each 28-day cycle. Gemcitabine: 1000 mg/m^2 administered IV over 30 minutes on Days 1, 8, 15, and 22 of Cycle 1 (28 days), and then Days 1, 8, and 15 of subsequent 28-day cycles.
BG001	Aflibercept/Gemcitabine	Aflibercept: 4 mg/kg was administered IV over 1 hour once every 2 weeks, on Days 1 and 15 of each 28-day cycle. Gemcitabine: 1000 mg/m^2 administered IV over 30 minutes on Days 1, 8, 15, and 22 of Cycle 1 (28 days), and then Days 1, 8, and 15 of subsequent 28-day cycles.
BG002	Total	Total of all reporting groups

ID	Term
D004067	Digestive System Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D004701	Endocrine Gland Neoplasms
D004066	Digestive System Diseases
D010182	Pancreatic Diseases
D004700	Endocrine System Diseases

ID	Term
D006571	Heterocyclic Compounds
D003841	Deoxycytidine
D003562	Cytidine
D011741	Pyrimidine Nucleosides
D011743	Pyrimidines
D006573	Heterocyclic Compounds, 1-Ring

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo and Gemcitabine	Placebo: 4 mg/kg was administered IV over 1 hour once every 2 weeks, on Days 1 and 15 of each 28-day cycle. Gemcitabine: 1000 mg/m^2 administered IV over 30 minutes on Days 1, 8, 15, and 22 of Cycle 1 (28 days), and then Days 1, 8, and 15 of subsequent 28-day cycles.			122	271	239	271
EG001	Aflibercept and Gemcitabine	Aflibercept: 4 mg/kg was administered IV over 1 hour once every 2 weeks, on Days 1 and 15 of each 28-day cycle. Gemcitabine: 1000 mg/m^2 administered IV over 30 minutes on Days 1, 8, 15, and 22 of Cycle 1 (28 days), and then Days 1, 8, and 15 of subsequent 28-day cycles.			148	270	249	270