A Study of Ramucirumab (LY3009806) in Combination With Pa... | NCT02514551

ID	Type	Description	Link
I4T-MC-JVCZ	Other Identifier	Eli Lilly and Company
2014-005067-32	EudraCT Number

Label	Type	Description	Intervention Names
12mg/kg Ramucirumab + 80 mg/m² Paclitaxel	Experimental	12 milligram per kilogram (mg/kg) ramucirumab administered intravenously (IV) on day 1 and day 15 (28 day cycles) in combination with 80 milligram per square meter (mg/m²) paclitaxel administered IV on day 1, day 8 and day 15.	Drug: Ramucirumab Drug: Paclitaxel
8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel	Active Comparator	8 mg/kg ramucirumab administered IV on day 1 and day 15 (28 day cycles) in combination with 80 mg/m² paclitaxel administered IV on day 1, day 8 and day 15.	Drug: Ramucirumab Drug: Paclitaxel

Name	Type	Description	Arm Group Labels	Other Names
Ramucirumab	Drug	Administered IV	12mg/kg Ramucirumab + 80 mg/m² Paclitaxel 8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel

Measure	Description	Time Frame
Progression Free Survival (PFS) in Ramucirumab 12mg/kg Arm I4T-MC-JVCZ	PFS was defined as time from the date of randomization(RD) to date of radiographic documentation of progression(RDP) or the date of death due to any cause, whichever is earlier as defined by RECIST v.1.1. Participants with no tumor progression and no death were censored at date of last adequate radiological assessment (AST) or date of RD(whichever is later).PD is at least a 20% increase in sum of diameters of target lesions,taking as reference the smallest sum on study.In addition to the relative increase of 20%,the sum must also demonstrate an absolute increase of at least 5 mm.The appearance of 1 or more new lesions is also considered progression.Non-Target PD is unequivocal progression of existing nontarget lesions.A participant with incomplete baseline disease had PFS time censored at the enrollment date.A participant not known to have died or have RDP as of the data inclusion cutoff date for the analysis had PFS time censored at date of the last complete RDP-free disease AST.	Randomization to Objective Progressive Disease or Death (Up To 21 Months)

Measure	Description	Time Frame
Progression Free Survival (PFS) Ramucirumab 12mg/kg Arm and 8mg/kg Arm in I4T-MC-JVCZ	PFS was defined as time from the date of randomization(RD) to date of radiographic documentation of progression(RDP) or the date of death due to any cause, whichever is earlier as defined by RECIST v.1.1. Participants with no tumor progression and no death were censored at date of last adequate radiological assessment(AST) or date of RD(whichever is later).PD is at least a 20% increase in sum of diameters of target lesions,taking as reference the smallest sum on study.In addition to the relative increase of 20%,the sum must also demonstrate an absolute increase of at least 5 mm.The appearance of 1 or more new lesions is also considered progression.Non-Target PD is unequivocal progression of existing nontarget lesions.A participant with incomplete baseline disease had PFS time censored at the enrollment date.A participant not known to have died or have RDP as of the data inclusion cutoff date for the analysis had PFS time censored at date of the last complete RDP-free disease AST.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

The participant has a diagnosis of gastric or GEJ adenocarcinoma.
The participant has disease progression during or within 4 months after last dose of first-line chemotherapy or during or within 6 months after the last dose of neoadjuvant or adjuvant therapy.
The participant received combination chemotherapy, which must include a platinum and/or a fluoropyrimidine and must not include a taxane or antiangiogenic agent.
The disease is evaluable by imaging per Response Evaluation Criteria in Solid Tumors 1.1.
The participant has an Eastern Cooperative Oncology Group performance status of 0 or 1.
The participant has adequate organ function:
- Total bilirubin ≤1.5 × the upper limit of normal (ULN) and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 × ULN. If the liver has tumor involvement, AST and ALT <5 × ULN.
- Serum creatinine ≤1.5 × ULN or calculated creatinine clearance ≥50 milliliters/minute.
- Urinary protein is <2+.
- Absolute neutrophil count ≥1.5 × 10^9/liter (L), platelets ≥100 × 10^9/L, and hemoglobin ≥9 grams/deciliter (5.58 millimoles/L).
- International normalized ratio ≤1.5 × ULN and partial thromboplastin time ≤5 seconds above ULN.
The participant has an estimated life expectancy of minimum 12 weeks.
The participant has resolution to Grade 1 or less by Common Terminology Criteria for Adverse Events Version 4.0, of all clinically significant toxic effects of previous therapy.
The participant, if male, is sterile or agrees to use a reliable method of birth control.
The participant, if female, is surgically sterile, is postmenopausal, or agrees to use a highly effective method of birth control.
The participant, if female and of child-bearing potential, must have a negative pregnancy test.

Exclusion Criteria:

The participant is receiving therapy with any of the following:
- Nonsteroidal anti-inflammatory agents.
- Other anti-platelet agents; Aspirin use at doses up to 325 milligrams (mg)/day is permitted.
The participant received radiotherapy within 14 days prior to randomization.
The participant received previous chemotherapy with a cumulative dose of >900 mg per meter squared (mg/m^2) of epirubicin or >400 mg/m^2 of doxorubicin.
The participant has documented brain metastases or leptomeningeal disease.
The participant has a significant bleeding disorder or vasculitis.
The participant experienced any arterial thromboembolic event within 6 months.
The participant has symptomatic congestive heart failure or symptomatic cardiac arrhythmia.
The participant has uncontrolled hypertension, despite antihypertensive intervention.
The participant underwent major surgery within 28 days.
The participant has a history of gastrointestinal perforation or fistula within 6 months.
The participant has a history of inflammatory bowel disease or Crohn's disease requiring medical intervention within 12 months.
The participant has bowel obstruction or history of chronic diarrhea that is considered clinically significant.
The participant has either of the following:
- Child-pugh B or C cirrhosis.
The participant has a serious illness or medical condition including:
- Human immunodeficiency virus infection.
The participant has a concurrent active malignancy other than the following:
- Nonmelanomatous skin cancer.
- In situ carcinoma of the cervix or other noninvasive carcinoma or in situ neoplasm.
The participant has a serious nonhealing: (a) wound, (b) peptic ulcer, or (c) bone fracture.
The participant experienced any Grade 3 or 4 venous thromboembolic event that is not adequately treated.

Name	Affiliation	Role
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)	Eli Lilly and Company	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
City of Hope National Medical Center		Duarte	California	91010-0269	United States
University of Kansas Medical Center

ID	Title	Description
FG000	12mg/kg Ramucirumab + 80 mg/m² Paclitaxel	12 milligram per kilogram (mg/kg) ramucirumab administered intravenously (IV) on day 1 and day 15 (28 day cycles) in combination with 80 milligram per square meter (mg/m²) paclitaxel administered IV on day 1, day 8 and day 15.
FG001	8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	May 7, 2015	Aug 10, 2018

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

Progression Free Survival (PFS) in Ramucirumab 12mg/kg Arm I4T-MC-JVCZ

PFS was defined as time from the date of randomization(RD) to date of radiographic documentation of progression(RDP) or the date of death due to any cause, whichever is earlier as defined by RECIST v.1.1. Participants with no tumor progression and no death were censored at date of last adequate radiological assessment (AST) or date of RD(whichever is later).PD is at least a 20% increase in sum of diameters of target lesions,taking as reference the smallest sum on study.In addition to the relative increase of 20%,the sum must also demonstrate an absolute increase of at least 5 mm.The appearance of 1 or more new lesions is also considered progression.Non-Target PD is unequivocal progression of existing nontarget lesions.A participant with incomplete baseline disease had PFS time censored at the enrollment date.A participant not known to have died or have RDP as of the data inclusion cutoff date for the analysis had PFS time censored at date of the last complete RDP-free disease AST.

All randomized participants in arm 12mg/kg Ramucirumab + 80 mg/m² Paclitaxel. Number of participants censored: Ramucirumab 12 mg/kg + 80 mg/m² Paclitaxel= 25. All randomized participants (including the censored participants) were included in the analyses.

Posted

Median

95% Confidence Interval

months

Randomization to Objective Progressive Disease or Death (Up To 21 Months)

ID	Title	Description
OG000	I4T-MC-JVCZ: 12mg/kg Ramucirumab + 80 mg/m² Paclitaxel	12mg/kg ramucirumab administered intravenously (IV) on day 1 and day 15 (28 day cycles) in combination with 80 mg/m² paclitaxel administered IV on day 1, day 8 and day 15.

Units	Counts
Participants	OG000123

Title

Denominators

Categories

Title	Measurements
	OG0005.42(4.40 to 6.01)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000	This analysis were comparison of PFS for participants treated with ramucirumab 12 mg/kg plus paclitaxel in Study I4T-MC-JVCZ versus placebo plus paclitaxel in I4T-IE-JVBE (NCT01170663) using meta-analysis. Placebo + 80 mg/m² Paclitaxel in I4T-IE-JVBE Number of participants: 335, Median (95% CI), months: 2.86 (2.79 to 3.02)					Hazard Ratio (HR)	0.617			2-Sided	95	0.447	0.853			Unstratified cox proportional hazards model comparing Ramucirumab I4T-MC-JVCZ and I4T-IE-JVBE (NCT01170663)		Superiority

Secondary

Progression Free Survival (PFS) Ramucirumab 12mg/kg Arm and 8mg/kg Arm in I4T-MC-JVCZ

PFS was defined as time from the date of randomization(RD) to date of radiographic documentation of progression(RDP) or the date of death due to any cause, whichever is earlier as defined by RECIST v.1.1. Participants with no tumor progression and no death were censored at date of last adequate radiological assessment(AST) or date of RD(whichever is later).PD is at least a 20% increase in sum of diameters of target lesions,taking as reference the smallest sum on study.In addition to the relative increase of 20%,the sum must also demonstrate an absolute increase of at least 5 mm.The appearance of 1 or more new lesions is also considered progression.Non-Target PD is unequivocal progression of existing nontarget lesions.A participant with incomplete baseline disease had PFS time censored at the enrollment date.A participant not known to have died or have RDP as of the data inclusion cutoff date for the analysis had PFS time censored at date of the last complete RDP-free disease AST.

All randomized participants. Number of participants censored: Ramucirumab 12 mg/kg + Paclitaxel 80 mg/m2= 25 and 8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel =23. All randomized participants (including the censored participants) were included in the analyses.

Posted

Median

95% Confidence Interval

months

Randomization to Objective Progressive Disease or Death (Up To 21 Months)

ID	Title	Description
OG000	12mg/kg Ramucirumab + 80 mg/m² Paclitaxel	12mg/kg ramucirumab administered intravenously (IV) on day 1 and day 15 (28 day cycles) in combination with 80 mg/m² paclitaxel administered IV on day 1, day 8 and day 15.

Secondary

Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab in Combination With Paclitaxel

Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab in Combination with Paclitaxel

All randomized participants who received at least one dose of study drug and had evaluable PK data.

Posted

Geometric Mean

Geometric Coefficient of Variation

Microgram per milliliter (µg/mL)

Cycle(C) 1 Day(D) 1: Prior to Infusion(PTI),1 to 1.5 hours(hrs) after end of Infusion(EOI); C1 D15: 3 days PTI; C2 D1: 3 days PTI; C2 D15: 3 days PTI,1 to 1.5 hrs after EOI; C3 D1 and 15: 3 days PTI; C4 D1: 3 days PTI and 1 to 1.5 hrs after EOI

ID	Title	Description
OG000	12mg/kg Ramucirumab + 80 mg/m² Paclitaxel	12mg/kg ramucirumab administered intravenously (IV) on day 1 and day 15 (28 day cycles) in combination with 80 mg/m² paclitaxel administered IV on day 1, day 8 and day 15.
OG001	8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel	8 mg/kg ramucirumab administered IV on day 1 and day 15 (28 day cycles) in combination with 80 mg/m² paclitaxel administered IV on day 1, day 8 and day 15.

Units	Counts
Participants

Secondary

Percentage of Participants Who Achieve Best Overall Tumor Response of Complete Response (CR) or Partial Response (PR) (Objective Response Rates [ORR])

ORR was defined as the percentage of participants who achieved a PR or CR per RECIST v.1.1.CR is the disappearance of all target lesions.Any pathological lymph nodes(whether target or non-target)must have reduction in short axis to<10mm.Tumor marker results must have normalized.PR is at least a 30% decrease in the sum of diameter of target lesions,taking as reference the baseline sum diameters.ORR is calculated as a total number of participants with CR or PR divided by the total number of participants treated multiplied by 100.

All randomized participants.

Posted

Number

percentage of participants

Baseline to Objective Progressive Disease (Up To 21 Months)

ID	Title	Description
OG000	12mg/kg Ramucirumab + 80 mg/m² Paclitaxel	12mg/kg ramucirumab administered intravenously (IV) on day 1 and day 15 (28 day cycles) in combination with 80 mg/m² paclitaxel administered IV on day 1, day 8 and day 15.
OG001	8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel	8 mg/kg ramucirumab administered IV on day 1 and day 15 (28 day cycles) in combination with 80 mg/m² paclitaxel administered IV on day 1, day 8 and day 15.

Secondary

Percentage of Participants Who Exhibit Stable Disease (SD) or Confirmed Response (CR) or Partial Response (PR) [Disease Control Rate (DCR)]

DCR is defined as the percentage of participants who achieved CR, PR, or SD per RECIST v.1.1. CR is the disappearance of all target lesions. Any pathological lymph nodes (target or non-target) must have reduction in short axis to <10 mm.Tumor marker results must have normalized. PR is at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.The appearance of 1 or more new lesions is also considered progression. Non-Target PD is unequivocal progression of existing nontarget lesions. DCR=CR+PR+SD/total number of participants*100.

All randomized participants.

Posted

Number

percentage of participants

Baseline to Objective Progressive Disease (Up To 21 Months)

ID	Title	Description
OG000	12mg/kg Ramucirumab + 80 mg/m² Paclitaxel	12mg/kg ramucirumab administered intravenously (IV) on day 1 and day 15 (28 day cycles) in combination with 80 mg/m² paclitaxel administered IV on day 1, day 8 and day 15.
OG001	8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel

Secondary

Number of Participants With Anti-Ramucirumab Antibodies

Participants who had anti-ramucirumab antibodies at postbaseline.

All randomized participants who received at least one dose of study drug and were evaluable for ramucirumab anti-drug antibody.

Posted

Count of Participants

Participants

Cycle 1 Predose through Follow-up (Up To 24 Months)

ID	Title	Description
OG000	12mg/kg Ramucirumab + 80 mg/m² Paclitaxel	12mg/kg ramucirumab administered intravenously (IV) on day 1 and day 15 (28 day cycles) in combination with 80 mg/m² paclitaxel administered IV on day 1, day 8 and day 15.
OG001	8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel	8 mg/kg ramucirumab administered IV on day 1 and day 15 (28 day cycles) in combination with 80 mg/m² paclitaxel administered IV on day 1, day 8 and day 15.

Units	Counts
Participants	OG000

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 21.1	Systematic Assessment	EG0003 events3 affected123 at risk EG0013 events3 affected120 at risk
Bone marrow failure	Blood and lymphatic system disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected123 at risk EG0012 events1 affected120 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 21.1	Systematic Assessment	EG0004 events4 affected123 at risk EG0013 events3 affected120 at risk
Leukocytosis	Blood and lymphatic system disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected123 at risk EG0010 events0 affected120 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected123 at risk EG0012 events1 affected120 at risk
Cardiac failure	Cardiac disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected123 at risk EG0010 events0 affected120 at risk
Cardiopulmonary failure	Cardiac disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected123 at risk EG0011 events1 affected120 at risk
Cardiovascular insufficiency	Cardiac disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected123 at risk EG0011 events1 affected120 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0005 events4 affected123 at risk EG0012 events2 affected120 at risk
Ascites	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected123 at risk EG0011 events1 affected120 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected123 at risk EG0011 events1 affected120 at risk
Dysphagia	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected123 at risk EG0010 events0 affected120 at risk
Gastric haemorrhage	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0006 events3 affected123 at risk EG0011 events1 affected120 at risk
Gastric perforation	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected123 at risk EG0011 events1 affected120 at risk
Gastric stenosis	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected123 at risk EG0010 events0 affected120 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0002 events2 affected123 at risk EG0010 events0 affected120 at risk
Haematemesis	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected123 at risk EG0010 events0 affected120 at risk
Ileus	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected123 at risk EG0012 events2 affected120 at risk
Large intestinal haemorrhage	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected123 at risk EG0010 events0 affected120 at risk
Nausea	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected123 at risk EG0010 events0 affected120 at risk
Oesophageal fistula	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected123 at risk EG0010 events0 affected120 at risk
Oesophageal haemorrhage	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected123 at risk EG0011 events1 affected120 at risk
Oesophageal obstruction	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected123 at risk EG0010 events0 affected120 at risk
Oesophageal perforation	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected123 at risk EG0011 events1 affected120 at risk
Pneumoperitoneum	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected123 at risk EG0011 events1 affected120 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected123 at risk EG0011 events1 affected120 at risk
Tongue oedema	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected123 at risk EG0010 events0 affected120 at risk
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected123 at risk EG0011 events1 affected120 at risk
Vomiting	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0003 events3 affected123 at risk EG0011 events1 affected120 at risk
Asthenia	General disorders	MedDRA 21.1	Systematic Assessment	EG0002 events2 affected123 at risk EG0010 events0 affected120 at risk
Death	General disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected123 at risk EG0010 events0 affected120 at risk
Fatigue	General disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected123 at risk EG0011 events1 affected120 at risk
General physical health deterioration	General disorders	MedDRA 21.1	Systematic Assessment	EG0002 events2 affected123 at risk EG0010 events0 affected120 at risk
Localised oedema	General disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected123 at risk EG0010 events0 affected120 at risk
Malaise	General disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected123 at risk EG0011 events1 affected120 at risk
Oedema	General disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected123 at risk EG0010 events0 affected120 at risk
Organ failure	General disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected123 at risk EG0010 events0 affected120 at risk
Pyrexia	General disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected123 at risk EG0010 events0 affected120 at risk
Cholangitis	Hepatobiliary disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected123 at risk EG0011 events1 affected120 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected123 at risk EG0011 events1 affected120 at risk
Cholecystitis acute	Hepatobiliary disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected123 at risk EG0010 events0 affected120 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected123 at risk EG0010 events0 affected120 at risk
Gallbladder rupture	Hepatobiliary disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected123 at risk EG0010 events0 affected120 at risk
Hepatitis toxic	Hepatobiliary disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected123 at risk EG0010 events0 affected120 at risk
Jaundice	Hepatobiliary disorders	MedDRA 21.1	Systematic Assessment	EG0003 events2 affected123 at risk EG0010 events0 affected120 at risk
Bacteraemia	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected123 at risk EG0011 events1 affected120 at risk
Bronchitis	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected123 at risk EG0011 events1 affected120 at risk
Clostridium difficile colitis	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected123 at risk EG0010 events0 affected120 at risk
Device related infection	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected123 at risk EG0011 events1 affected120 at risk
Enteritis infectious	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected123 at risk EG0010 events0 affected120 at risk
Escherichia infection	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected123 at risk EG0011 events1 affected120 at risk
Infection	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0002 events2 affected123 at risk EG0010 events0 affected120 at risk
Lung infection	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected123 at risk EG0011 events1 affected120 at risk
Peritonitis	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected123 at risk EG0011 events1 affected120 at risk
Pneumonia	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected123 at risk EG0012 events1 affected120 at risk
Pneumonia necrotising	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected123 at risk EG0011 events1 affected120 at risk
Respiratory tract infection	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected123 at risk EG0010 events0 affected120 at risk
Sepsis	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected123 at risk EG0010 events0 affected120 at risk
Septic shock	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected123 at risk EG0010 events0 affected120 at risk
Femoral neck fracture	Injury, poisoning and procedural complications	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected123 at risk EG0011 events1 affected120 at risk
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected123 at risk EG0010 events0 affected120 at risk
Tibia fracture	Injury, poisoning and procedural complications	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected123 at risk EG0010 events0 affected120 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected123 at risk EG0010 events0 affected120 at risk
Blood bilirubin increased	Investigations	MedDRA 21.1	Systematic Assessment	EG0002 events2 affected123 at risk EG0010 events0 affected120 at risk
Neutrophil count decreased	Investigations	MedDRA 21.1	Systematic Assessment	EG0006 events6 affected123 at risk EG0010 events0 affected120 at risk
Cachexia	Metabolism and nutrition disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected123 at risk EG0010 events0 affected120 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected123 at risk EG0011 events1 affected120 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected123 at risk EG0011 events1 affected120 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected123 at risk EG0010 events0 affected120 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected123 at risk EG0010 events0 affected120 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected123 at risk EG0010 events0 affected120 at risk
Malnutrition	Metabolism and nutrition disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected123 at risk EG0010 events0 affected120 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected123 at risk EG0011 events1 affected120 at risk
Lymphangiosis carcinomatosa	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected123 at risk EG0011 events1 affected120 at risk
Tumour haemorrhage	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected123 at risk EG0011 events1 affected120 at risk
Tumour perforation	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected123 at risk EG0010 events0 affected120 at risk
Syncope	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected123 at risk EG0011 events1 affected120 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 21.1	Systematic Assessment	EG0002 events1 affected123 at risk EG0010 events0 affected120 at risk
Proteinuria	Renal and urinary disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected123 at risk EG0011 events1 affected120 at risk
Renal failure	Renal and urinary disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected123 at risk EG0010 events0 affected120 at risk
Oedema genital	Reproductive system and breast disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected123 at risk EG0010 events0 affected120 at risk
Aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected123 at risk EG0011 events1 affected120 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG0002 events1 affected123 at risk EG0011 events1 affected120 at risk
Hiccups	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected123 at risk EG0010 events0 affected120 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected123 at risk EG0011 events1 affected120 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected123 at risk EG0011 events1 affected120 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected123 at risk EG0010 events0 affected120 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected123 at risk EG0011 events1 affected120 at risk
Pulmonary hypertension	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected123 at risk EG0011 events1 affected120 at risk
Respiratory distress	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected123 at risk EG0011 events1 affected120 at risk
Hypotension	Vascular disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected123 at risk EG0011 events1 affected120 at risk
Shock haemorrhagic	Vascular disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected123 at risk EG0010 events0 affected120 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 21.1	Systematic Assessment	EG00072 events34 affected123 at risk EG00177 events39 affected120 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA 21.1	Systematic Assessment	EG00044 events9 affected123 at risk EG00118 events9 affected120 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 21.1	Systematic Assessment	EG00078 events22 affected123 at risk EG00162 events24 affected120 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 21.1	Systematic Assessment	EG00010 events7 affected123 at risk EG0015 events4 affected120 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0009 events7 affected123 at risk EG0018 events6 affected120 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG00031 events20 affected123 at risk EG00122 events19 affected120 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG00013 events8 affected123 at risk EG00116 events12 affected120 at risk
Ascites	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG00011 events9 affected123 at risk EG0018 events5 affected120 at risk
Constipation	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG00033 events23 affected123 at risk EG00127 events21 affected120 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG00078 events31 affected123 at risk EG00165 events35 affected120 at risk
Dysphagia	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG00012 events11 affected123 at risk EG0014 events4 affected120 at risk
Nausea	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG00052 events27 affected123 at risk EG00195 events38 affected120 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG00019 events15 affected123 at risk EG00141 events18 affected120 at risk
Vomiting	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG00051 events29 affected123 at risk EG00144 events27 affected120 at risk
Asthenia	General disorders	MedDRA 21.1	Systematic Assessment	EG00035 events15 affected123 at risk EG00149 events19 affected120 at risk
Fatigue	General disorders	MedDRA 21.1	Systematic Assessment	EG00085 events43 affected123 at risk EG00182 events46 affected120 at risk
Oedema peripheral	General disorders	MedDRA 21.1	Systematic Assessment	EG00011 events10 affected123 at risk EG00122 events16 affected120 at risk
Pyrexia	General disorders	MedDRA 21.1	Systematic Assessment	EG00010 events9 affected123 at risk EG0018 events8 affected120 at risk
Alanine aminotransferase increased	Investigations	MedDRA 21.1	Systematic Assessment	EG00027 events14 affected123 at risk EG0018 events7 affected120 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 21.1	Systematic Assessment	EG00043 events20 affected123 at risk EG00115 events8 affected120 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA 21.1	Systematic Assessment	EG00025 events9 affected123 at risk EG00114 events10 affected120 at risk
Blood bilirubin increased	Investigations	MedDRA 21.1	Systematic Assessment	EG00012 events8 affected123 at risk EG0013 events2 affected120 at risk
Neutrophil count decreased	Investigations	MedDRA 21.1	Systematic Assessment	EG00091 events30 affected123 at risk EG00160 events24 affected120 at risk
Platelet count decreased	Investigations	MedDRA 21.1	Systematic Assessment	EG00015 events9 affected123 at risk EG00113 events7 affected120 at risk
Weight decreased	Investigations	MedDRA 21.1	Systematic Assessment	EG00016 events14 affected123 at risk EG00117 events13 affected120 at risk
White blood cell count decreased	Investigations	MedDRA 21.1	Systematic Assessment	EG00033 events13 affected123 at risk EG00135 events14 affected120 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 21.1	Systematic Assessment	EG00041 events25 affected123 at risk EG00158 events32 affected120 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 21.1	Systematic Assessment	EG00018 events8 affected123 at risk EG00120 events11 affected120 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA 21.1	Systematic Assessment	EG00013 events10 affected123 at risk EG00134 events14 affected120 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 21.1	Systematic Assessment	EG00013 events7 affected123 at risk EG0018 events7 affected120 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 21.1	Systematic Assessment	EG00013 events8 affected123 at risk EG0015 events5 affected120 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 21.1	Systematic Assessment	EG00013 events10 affected123 at risk EG00114 events9 affected120 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 21.1	Systematic Assessment	EG00018 events11 affected123 at risk EG00116 events9 affected120 at risk
Dysgeusia	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG0005 events5 affected123 at risk EG00113 events9 affected120 at risk
Headache	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG00012 events10 affected123 at risk EG00112 events9 affected120 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG00038 events15 affected123 at risk EG00122 events15 affected120 at risk
Paraesthesia	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG00030 events13 affected123 at risk EG00129 events13 affected120 at risk
Peripheral sensory neuropathy	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG00015 events8 affected123 at risk EG00146 events20 affected120 at risk
Proteinuria	Renal and urinary disorders	MedDRA 21.1	Systematic Assessment	EG00019 events9 affected123 at risk EG00111 events8 affected120 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG00017 events14 affected123 at risk EG00111 events8 affected120 at risk
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG00015 events11 affected123 at risk EG0017 events6 affected120 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG0005 events4 affected123 at risk EG00113 events12 affected120 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG00043 events26 affected123 at risk EG00136 events28 affected120 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 21.1	Systematic Assessment	EG00019 events19 affected123 at risk EG00128 events24 affected120 at risk
Hypertension	Vascular disorders	MedDRA 21.1	Systematic Assessment	EG00044 events24 affected123 at risk EG00146 events21 affected120 at risk

ID	Term
D005770	Gastrointestinal Neoplasms
D004067	Digestive System Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D004066	Digestive System Diseases
D005767	Gastrointestinal Diseases
D013272	Stomach Diseases

ID	Term
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins
D043823	Taxoids
D043822	Cyclodecanes
D003516	Cycloparaffins
D006840	Hydrocarbons, Alicyclic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D009930	Organic Chemicals
D004224	Diterpenes
D013729	Terpenes

ID	Title	Description
BG000	12mg/kg Ramucirumab + 80 mg/m² Paclitaxel	12mg/kg ramucirumab administered intravenously (IV) on day 1 and day 15 (28 day cycles) in combination with 80 mg/m² paclitaxel administered IV on day 1, day 8 and day 15.
BG001	8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel	8 mg/kg ramucirumab administered IV on day 1 and day 15 (28 day cycles) in combination with 80 mg/m² paclitaxel administered IV on day 1, day 8 and day 15.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	12mg/kg Ramucirumab + 80 mg/m² Paclitaxel	12mg/kg ramucirumab administered intravenously (IV) on day 1 and day 15 (28 day cycles) in combination with 80 mg/m² paclitaxel administered IV on day 1, day 8 and day 15.	81	123	47	123	117	123
EG001	8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel	8 mg/kg ramucirumab administered IV on day 1 and day 15 (28 day cycles) in combination with 80 mg/m² paclitaxel administered IV on day 1, day 8 and day 15.	76	120	32	120	115	120