A Study of Ramucirumab in Participants With Gastric, Esop... | NCT01246960

ID	Type	Description	Link
I4T-MC-JVBT	Other Identifier	Eli Lilly and Company

Label	Type	Description	Intervention Names
Ramucirumab	Experimental	Oxaliplatin 85 milligrams per square meter (mg/m^2) given on Day 1 of a 2-week cycle Leucovorin 400 mg/m^2 given on Day 1 of a 2-week cycle 5-Fluorouracil (5-FU) 400 mg/m^2 bolus given on Day 1 of a 2-week cycle 5-FU 2400 mg/m^2 continuously given over 46-48 hours on Day 1 of a 2-week cycle Ramucirumab 8 milligrams per kilogram (mg/kg) given on Day 1 of a 2-week cycle Participants will receive study treatment every 2 weeks until disease progression, unacceptable toxicity, or another withdrawal criterion is met	Biological: Ramucirumab Drug: Oxaliplatin Drug: Leucovorin Drug: 5-Fluorouracil
Placebo	Placebo Comparator	Oxaliplatin 85 mg/m^2 given on Day 1 of a 2-week cycle Leucovorin 400 mg/m^2 given on Day 1 of a 2-week cycle 5-FU 400 mg/m^2 bolus given on Day 1 of a 2-week cycle 5-FU 2400 mg/m^2 continuously given over 46-48 hours on Day 1 of a 2-week cycle Placebo given on Day 1 of a 2-week cycle Participants will receive study treatment every 2 weeks until disease progression, unacceptable toxicity, or another withdrawal criterion is met	Drug: Placebo Drug: Oxaliplatin Drug: Leucovorin Drug: 5-Fluorouracil

Name	Type	Description	Arm Group Labels	Other Names
Ramucirumab	Biological	Administered intravenously	Ramucirumab	LY3009806

Measure	Description	Time Frame
Progression-Free Survival (PFS)	PFS was defined using Response Evaluation Criteria in Solid Tumors [RECIST version (v.) 1.1] as the time from randomization to the first observation of progressive disease (PD) or death due to any cause, whichever came first. PD was a ≥20% increase in the sum of the diameters of target lesions with the sum demonstrating an absolute increase of ≥5 millimeters (mm); the appearance of ≥1 new lesions or unequivocal progression of non-target lesions. If a participant did not have a baseline disease assessment, PFS time was censored at the randomization date, regardless of whether or not PD or death was observed. Participants not known to have died or have objective PD were censored at the last post-baseline radiological assessment date.	Randomization to measured PD or date of death from any cause (up to Month 25.0)

Measure	Description	Time Frame
Overall Survival (OS)	OS was defined as the time from randomization to death due to any cause. OS was censored at the date of the last follow-up visit for participants who were alive or lost to follow-up.	Randomization to date of death from any cause (up to Month 28.3)
Percentage of Participants Achieving an Objective Response (Objective Response Rate)

Measure	Description	Time Frame
Number of Participants With Adverse Events (AEs)	Reported are the number of participants who had ramucirumab/placebo-related: AEs, serious AEs (SAEs), AEs based on common terminology criteria for adverse events (CTCAE) ≥Grade 3, AEs = CTCAE Grade 5, as well as, AEs leading to treatment discontinuation and AEs resulting in death. A summary of serious and other non-serious AEs regardless of causality is located in the Reported Adverse Events module.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Histologic or cytologic confirmation of adenocarcinoma of the esophagus, gastroesophageal junction (GEJ), or stomach
Metastatic or locally advanced, unresectable disease at time of study entry
Provided signed informed consent and is amenable to compliance with protocol schedules and testing
Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-1 at study entry
Adequate renal, hematological, and hepatic function
Measurable or non-measurable disease at the time of study entry
Resolution to Grade less than or equal to 1 by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.0, of all clinically significant toxic effects of prior locoregional therapy, surgery, or other anticancer therapy, except where otherwise mentioned in the eligibility criteria
Eligible participants of reproductive potential (both sexes) must agree to use adequate contraceptive methods (hormonal or barrier methods) during the study period and at least 12 weeks after the last dose of study therapy
Life expectancy of greater than or equal to 3 months
Willingness to provide blood and tissue samples for research purposes. Submission of tumor specimen is mandatory for participation in this study, if a histologic, paraffin-embedded specimen exists (either from a surgical resection or biopsy); submission of paraffin block or a minimum of 8 unstained slides is required if sufficient sample. NOTE: If insufficient additional tissue exists (that is, all tissue has been utilized for prior diagnostic purposes), participation in the study is allowable without the requirement for an additional biopsy; this situation must be discussed with the study principal investigator and/or the ImClone medical monitor or designee.

Exclusion Criteria:

The participant has received prior first-line systemic therapy for advanced/unresectable and/or metastatic disease (prior adjuvant or neo-adjuvant therapy is permitted)
Previous or concurrent malignancy except for basal or squamous cell skin cancer and/or in situ carcinoma of the cervix, or other solid tumors treated curatively and without evidence of recurrence for at least 3 years prior to study entry
Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the participant ineligible for entry into this study
The participant is receiving chronic therapy with nonsteroidal anti-inflammatory agents (NSAIDs; for example, indomethacin, ibuprofen, naproxen, or similar agents) or other antiplatelet agents (for example, clopidogrel, ticlopidine, dipyridamole, anagrelide). Aspirin use at doses up to 325 milligrams per day (mg/day) is permitted.
The participant has significant third-space fluid retention (for example, ascites or pleural effusion), and is not amenable for required repeated drainage
The participant is pregnant or breastfeeding
Uncontrolled intercurrent illness including, but not limited to, active or uncontrolled clinically serious infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled thromboembolic, or hemorrhagic disorder, psychiatric illness/social situations, or other co-morbid systemic illnesses, or other severe concurrent disease
Immunocompromised participants including participants known to be human immunodeficiency virus (HIV) positive.
Progressive disease less than or equal to 12 months of completing platinum or 5-FU treatment, including capecitabine, if given previously in the perioperative (adjuvant or neoadjuvant) setting
Current or recent (within 28 days prior to randomization) treatment with an investigational drug that has not received regulatory approval for any indication at the time of study entry, or participation in another interventional clinical trial. Participants participating in surveys or observational studies are eligible to participate in this study.
Are currently enrolled in, or discontinued within the last 28 days from, a clinical trial involving ramucirumab drug product (DP), or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
Received prior therapy with an antiangiogenic agent (including but not limited to bevacizumab, sunitinib, or sorafenib)
Major surgical procedure or significant traumatic injury less than 28 days prior to randomization, or anticipation of need for elective or planned major surgical procedure during the course of the study. Subcutaneous venous access device placement within 7 days prior to randomization
Clinically significant peripheral neuropathy at the time of registration
Known central nervous system metastases that are symptomatic or untreated
New York Heart Association (NYHA) classification III-IV congestive heart failure
Greater than normal risk of bleeding or coagulopathy in the absence of therapeutic anticoagulation; Grade 3/4 gastrointestinal bleeding within 3 months prior to registration; active bleeding (that is, within 14 days prior to first dose of study therapy); or pathological condition present that carries a high risk of bleeding (for example, tumor involving major vessels or known varices)
Participant has experienced any arterial thromboembolic events, including but not limited to myocardial infarction, stroke, transient ischemic attack (TIA), cerebrovascular accident, or unstable angina, less than or equal to 6 months prior to registration
Clinically significant vascular disease (for example, aortic aneurysm, aortic dissection) for which more than minimal intervention is being administered or planned
History of hypertensive crisis or hypertensive encephalopathy or current poorly-controlled hypertension despite standard medical management
History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess less than 6 months prior to registration
Known hypersensitivity to any of the treatment components of modified FOLFOX6 (mFOLFOX6) (oxaliplatin, 5-FU, and leucovorin) or ramucirumab DP

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
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.		Anchorage	Alaska	99508

PubMed Identifier	Type	Citation	Retractions
27765757	Derived	Yoon HH, Bendell JC, Braiteh FS, Firdaus I, Philip PA, Cohn AL, Lewis N, Anderson DM, Arrowsmith E, Schwartz JD, Gao L, Hsu Y, Xu Y, Ferry D, Alberts SR, Wainberg ZA. Ramucirumab combined with FOLFOX as front-line therapy for advanced esophageal, gastroesophageal junction, or gastric adenocarcinoma: a randomized, double-blind, multicenter Phase II trial. Ann Oncol. 2016 Dec;27(12):2196-2203. doi: 10.1093/annonc/mdw423. Epub 2016 Oct 20.

ID	Title	Description
FG000	Ramucirumab and mFOLFOX6	Ramucirumab: 8 milligrams per kilogram (mg/kg) intravenous infusion administered on Day 1 of each cycle (14 days/cycle). In Cycles 1 and 2, there was a 1-hour observation prior to administering modified FOLFOX6 (mFOLFOX6). mFOLFOX6: Administered intravenously per manufacturer's instructions for each drug substance on Day 1 of each cycle (14 days/cycle). Oxaliplatin 85 milligrams per square meter (mg/m^2) Leucovorin 400 mg/m^2 5-Fluorouracil (5-FU) 400 mg/m^2 bolus 5-FU 2400 mg/m^2 continuous given over 46-48 hours Participants received study treatment every 2 weeks until disease progression, unacceptable toxicity, or another withdrawal criterion was met.

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)

PFS was defined using Response Evaluation Criteria in Solid Tumors [RECIST version (v.) 1.1] as the time from randomization to the first observation of progressive disease (PD) or death due to any cause, whichever came first. PD was a ≥20% increase in the sum of the diameters of target lesions with the sum demonstrating an absolute increase of ≥5 millimeters (mm); the appearance of ≥1 new lesions or unequivocal progression of non-target lesions. If a participant did not have a baseline disease assessment, PFS time was censored at the randomization date, regardless of whether or not PD or death was observed. Participants not known to have died or have objective PD were censored at the last post-baseline radiological assessment date.

ITT population: all randomized participants. Fourteen participants in the Ramucirumab and mFOLFOX6 treatment arm and 15 participants in the Placebo and mFOLFOX6 treatment arm were censored.

Median

95% Confidence Interval

months

Randomization to measured PD or date of death from any cause (up to Month 25.0)

ID	Title	Description
OG000	Ramucirumab and mFOLFOX6	Ramucirumab: 8 mg/kg intravenous infusion administered on Day 1 of each cycle (14 days/cycle). In Cycles 1 and 2, there was a 1-hour observation prior to administering mFOLFOX6. mFOLFOX6: Administered intravenously per manufacturer's instructions for each drug substance on Day 1 of each cycle (14 days/cycle). Oxaliplatin: 85 mg/m^2 Leucovorin: 400 mg/m^2 5-FU: 400 mg/m^2 bolus 5-FU: 2400 mg/m^2 continuous given over 46-48 hours Participants received study treatment every 2 weeks until disease progression, unacceptable toxicity, or another withdrawal criterion was met.
OG001	Placebo and mFOLFOX6	Placebo: intravenous infusion administered on Day 1 of each cycle (14 days/cycle). In Cycles 1 and 2, there was a 1-hour observation prior to administering mFOLFOX6. mFOLFOX6: Administered intravenously per manufacturer's instructions for each drug substance on Day 1 of each cycle (14 days/cycle). Oxaliplatin: 85 mg/m^2 Leucovorin: 400 mg/m^2 5-FU: 400 mg/m^2 bolus 5-FU: 2400 mg/m^2 continuous given over 46-48 hours Participants received study treatment every 2 weeks until disease progression, unacceptable toxicity, or another withdrawal criterion was met.

Units	Counts
Participants	OG00084 OG00184

Title

Denominators

Categories

Title	Measurements
	OG0006.4(5.8 to 9.3) OG0016.7(5.6 to 7.8)

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 OG001		Stratified Log Rank		0.886		Hazard Ratio (HR)	0.98			2-Sided	95	0.69	1.37				No	Superiority or Other

Secondary

Overall Survival (OS)

OS was defined as the time from randomization to death due to any cause. OS was censored at the date of the last follow-up visit for participants who were alive or lost to follow-up.

ITT population: all randomized participants. Twenty-seven participants in the Ramucirumab and mFOLFOX6 treatment arm and 32 participants in the Placebo and mFOLFOX6 treatment arm were censored.

Median

95% Confidence Interval

months

Randomization to date of death from any cause (up to Month 28.3)

ID	Title	Description
OG000	Ramucirumab and mFOLFOX6	Ramucirumab: 8 mg/kg intravenous infusion administered on Day 1 of each cycle (14 days/cycle). In Cycles 1 and 2, there was a 1-hour observation prior to administering mFOLFOX6. mFOLFOX6: Administered intravenously per manufacturer's instructions for each drug substance on Day 1 of each cycle (14 days/cycle). Oxaliplatin: 85 mg/m^2 Leucovorin: 400 mg/m^2 5-FU: 400 mg/m^2 bolus 5-FU: 2400 mg/m^2 continuous given over 46-48 hours Participants received study treatment every 2 weeks until disease progression, unacceptable toxicity, or another withdrawal criterion was met.
OG001	Placebo and mFOLFOX6	Placebo: intravenous infusion administered on Day 1 of each cycle (14 days/cycle). In Cycles 1 and 2, there was a 1-hour observation prior to administering mFOLFOX6. mFOLFOX6: Administered intravenously per manufacturer's instructions for each drug substance on Day 1 of each cycle (14 days/cycle). Oxaliplatin: 85 mg/m^2 Leucovorin: 400 mg/m^2 5-FU: 400 mg/m^2 bolus 5-FU: 2400 mg/m^2 continuous given over 46-48 hours Participants received study treatment every 2 weeks until disease progression, unacceptable toxicity, or another withdrawal criterion was met.

Secondary

Percentage of Participants Achieving an Objective Response (Objective Response Rate)

The percentage of participants who achieved a best overall response of partial response (PR) or complete response (CR) is reported. Response was defined using RECIST, v. 1.1 criteria. CR was the disappearance of all lesions and pathological lymph node reduction in the short axis to <10 mm. PR was a ≥30% decrease in the sum of the diameters of target lesions. The percentage of participants with objective response=(number of participants whose best overall response achieved was CR or PR/number of participants treated)*100.

ITT population: all randomized participants.

Number

95% Confidence Interval

percentage of participants

Randomization to measured PD (up to Month 23.0)

ID	Title	Description
OG000	Ramucirumab and mFOLFOX6	Ramucirumab: 8 mg/kg intravenous infusion administered on Day 1 of each cycle (14 days/cycle). In Cycles 1 and 2, there was a 1-hour observation prior to administering mFOLFOX6. mFOLFOX6: Administered intravenously per manufacturer's instructions for each drug substance on Day 1 of each cycle (14 days/cycle). Oxaliplatin: 85 mg/m^2 Leucovorin: 400 mg/m^2 5-FU: 400 mg/m^2 bolus 5-FU: 2400 mg/m^2 continuous given over 46-48 hours Participants received study treatment every 2 weeks until disease progression, unacceptable toxicity, or another withdrawal criterion was met.
OG001	Placebo and mFOLFOX6	Placebo: intravenous infusion administered on Day 1 of each cycle (14 days/cycle). In Cycles 1 and 2, there was a 1-hour observation prior to administering mFOLFOX6. mFOLFOX6: Administered intravenously per manufacturer's instructions for each drug substance on Day 1 of each cycle (14 days/cycle). Oxaliplatin: 85 mg/m^2 Leucovorin: 400 mg/m^2 5-FU: 400 mg/m^2 bolus 5-FU: 2400 mg/m^2 continuous given over 46-48 hours Participants received study treatment every 2 weeks until disease progression, unacceptable toxicity, or another withdrawal criterion was met.

Secondary

Duration of Response

Duration of response was defined using RECIST v. 1.1 criteria as the time from the date criteria were met for the first objectively recorded CR or PR until the first date criteria for PD were met or death from any cause. CR was the disappearance of all lesions and pathological lymph node reduction in the short axis to <10 mm. PR was a ≥30% decrease in the sum of the diameters of target lesions. PD was a ≥20% increase in the sum of the diameters of target lesions with the sum demonstrating an absolute increase of ≥5 mm; the appearance of ≥1 new lesions or unequivocal progression of non-target lesions. Participants who were not known to have died and who did not have PD were censored at the date of the last tumor assessment prior to the date of any subsequent systemic anticancer therapy.

Randomized participants who achieved an objective response of CR or PR. Eight participants in the Ramucirumab and mFOLFOX6 treatment arm and 8 participants in the Placebo and mFOLFOX6 treatment arm were censored.

Median

95% Confidence Interval

months

Time of first response to measured PD (up to Month 23.0)

ID	Title	Description
OG000	Ramucirumab and mFOLFOX6	Ramucirumab: 8 mg/kg intravenous infusion administered on Day 1 of each cycle (14 days/cycle). In Cycles 1 and 2, there was a 1-hour observation prior to administering mFOLFOX6. mFOLFOX6: Administered intravenously per manufacturer's instructions for each drug substance on Day 1 of each cycle (14 days/cycle). Oxaliplatin: 85 mg/m^2 Leucovorin: 400 mg/m^2 5-FU: 400 mg/m^2 bolus 5-FU: 2400 mg/m^2 continuous given over 46-48 hours Participants received study treatment every 2 weeks until disease progression, unacceptable toxicity, or another withdrawal criterion was met.

Secondary

Time to Disease Progression (TTP)

TTP was defined using RECIST v. 1.1 as the time from study randomization to the first date of PD. PD was a ≥20% increase in the sum of the diameters of target lesions with the sum demonstrating an absolute increase of ≥5 mm; the appearance of ≥1 new lesions or unequivocal progression of non-target lesions. TTP was censored at the date of last adequate tumor assessment if death was due to causes other than PD.

ITT population: all randomized participants. Thirty-five participants in the Ramucirumab and mFOLFOX6 treatment arm and 31 participants in the Placebo and mFOLFOX6 treatment arm were censored.

Median

Full Range

months

Randomization to measured PD (up to Month 25.0)

ID	Title	Description
OG000	Ramucirumab and mFOLFOX6	Ramucirumab: 8 mg/kg intravenous infusion administered on Day 1 of each cycle (14 days/cycle). In Cycles 1 and 2, there was a 1-hour observation prior to administering mFOLFOX6. mFOLFOX6: Administered intravenously per manufacturer's instructions for each drug substance on Day 1 of each cycle (14 days/cycle). Oxaliplatin: 85 mg/m^2 Leucovorin: 400 mg/m^2 5-FU: 400 mg/m^2 bolus 5-FU: 2400 mg/m^2 continuous given over 46-48 hours Participants received study treatment every 2 weeks until disease progression, unacceptable toxicity, or another withdrawal criterion was met.
OG001	Placebo and mFOLFOX6	Placebo: intravenous infusion administered on Day 1 of each cycle (14 days/cycle). In Cycles 1 and 2, there was a 1-hour observation prior to administering mFOLFOX6. mFOLFOX6: Administered intravenously per manufacturer's instructions for each drug substance on Day 1 of each cycle (14 days/cycle). Oxaliplatin: 85 mg/m^2 Leucovorin: 400 mg/m^2 5-FU: 400 mg/m^2 bolus 5-FU: 2400 mg/m^2 continuous given over 46-48 hours Participants received study treatment every 2 weeks until disease progression, unacceptable toxicity, or another withdrawal criterion was met.

Secondary

Number of Participants With Treatment-Emergent Anti-Ramucirumab Antibodies

Participants with treatment-emergent anti-ramucirumab antibodies were participants with a 4-fold increase (2 dilution increase) in immunogenicity titer over baseline titer, or participants who tested negative at baseline and positive post-baseline (at titer of ≥1:20).

Randomized participants who received any quantity of ramucirumab or placebo, and were evaluated for the presence of anti-ramucirumab antibodies.

Number

participants

Months 1, 2, 4, 6, and 8

ID	Title	Description
OG000	Ramucirumab and mFOLFOX6	Ramucirumab: 8 mg/kg intravenous infusion administered on Day 1 of each cycle (14 days/cycle). In Cycles 1 and 2, there was a 1-hour observation prior to administering mFOLFOX6. mFOLFOX6: Administered intravenously per manufacturer's instructions for each drug substance on Day 1 of each cycle (14 days/cycle). Oxaliplatin: 85 mg/m^2 Leucovorin: 400 mg/m^2 5-FU: 400 mg/m^2 bolus 5-FU: 2400 mg/m^2 continuous given over 46-48 hours Participants received study treatment every 2 weeks until disease progression, unacceptable toxicity, or another withdrawal criterion was met.
OG001	Placebo and mFOLFOX6	Placebo: intravenous infusion administered on Day 1 of each cycle (14 days/cycle). In Cycles 1 and 2, there was a 1-hour observation prior to administering mFOLFOX6. mFOLFOX6: Administered intravenously per manufacturer's instructions for each drug substance on Day 1 of each cycle (14 days/cycle). Oxaliplatin: 85 mg/m^2 Leucovorin: 400 mg/m^2 5-FU: 400 mg/m^2 bolus 5-FU: 2400 mg/m^2 continuous given over 46-48 hours Participants received study treatment every 2 weeks until disease progression, unacceptable toxicity, or another withdrawal criterion was met.

Other Pre-specified

Number of Participants With Adverse Events (AEs)

Reported are the number of participants who had ramucirumab/placebo-related: AEs, serious AEs (SAEs), AEs based on common terminology criteria for adverse events (CTCAE) ≥Grade 3, AEs = CTCAE Grade 5, as well as, AEs leading to treatment discontinuation and AEs resulting in death. A summary of serious and other non-serious AEs regardless of causality is located in the Reported Adverse Events module.

Safety population: randomized participants who received any quantity of study drug (Ramucirumab, mFOLFOX6, or placebo).

Number

participants

Baseline through study completion (up to Month 28.3)

ID	Title	Description
OG000	Ramucirumab and mFOLFOX6	Ramucirumab: 8 mg/kg intravenous infusion administered on Day 1 of each cycle (14 days/cycle). In Cycles 1 and 2, there was a 1-hour observation prior to administering mFOLFOX6. mFOLFOX6: Administered intravenously per manufacturer's instructions for each drug substance on Day 1 of each cycle (14 days/cycle). Oxaliplatin: 85 mg/m^2 Leucovorin: 400 mg/m^2 5-FU: 400 mg/m^2 bolus 5-FU: 2400 mg/m^2 continuous given over 46-48 hours Participants received study treatment every 2 weeks until disease progression, unacceptable toxicity, or another withdrawal criterion was met.
OG001	Placebo and mFOLFOX6	Placebo: intravenous infusion administered on Day 1 of each cycle (14 days/cycle). In Cycles 1 and 2, there was a 1-hour observation prior to administering mFOLFOX6. mFOLFOX6: Administered intravenously per manufacturer's instructions for each drug substance on Day 1 of each cycle (14 days/cycle). Oxaliplatin: 85 mg/m^2 Leucovorin: 400 mg/m^2 5-FU: 400 mg/m^2 bolus 5-FU: 2400 mg/m^2 continuous given over 46-48 hours Participants received study treatment every 2 weeks until disease progression, unacceptable toxicity, or another withdrawal criterion was met.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 12.0	Systematic Assessment	EG0005 events3 affected82 at risk EG0010 events0 affected80 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 12.0	Systematic Assessment	EG0003 events3 affected82 at risk EG0012 events2 affected80 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 12.0	Systematic Assessment	EG0003 events2 affected82 at risk EG0010 events0 affected80 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected82 at risk EG0010 events0 affected80 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected82 at risk EG0010 events0 affected80 at risk
Arteriospasm coronary	Cardiac disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected82 at risk EG0010 events0 affected80 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected82 at risk EG0012 events2 affected80 at risk
Bradycardia	Cardiac disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected82 at risk EG0011 events1 affected80 at risk
Cardiac tamponade	Cardiac disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected82 at risk EG0011 events1 affected80 at risk
Myocardial infarction	Cardiac disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected82 at risk EG0010 events0 affected80 at risk
Pericardial effusion	Cardiac disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected82 at risk EG0010 events0 affected80 at risk
Sinus bradycardia	Cardiac disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected82 at risk EG0010 events0 affected80 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected82 at risk EG0010 events0 affected80 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected82 at risk EG0010 events0 affected80 at risk
Ascites	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected82 at risk EG0010 events0 affected80 at risk
Constipation	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected82 at risk EG0011 events1 affected80 at risk
Dysphagia	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0002 events1 affected82 at risk EG0011 events1 affected80 at risk
Enteritis	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected82 at risk EG0011 events1 affected80 at risk
Gastric haemorrhage	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0002 events2 affected82 at risk EG0010 events0 affected80 at risk
Gastric perforation	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected82 at risk EG0010 events0 affected80 at risk
Gastrointestinal disorder	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected82 at risk EG0010 events0 affected80 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0004 events4 affected82 at risk EG0013 events3 affected80 at risk
Gastrointestinal obstruction	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected82 at risk EG0011 events1 affected80 at risk
Ileus	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0002 events1 affected82 at risk EG0011 events1 affected80 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected82 at risk EG0010 events0 affected80 at risk
Nausea	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0006 events5 affected82 at risk EG0012 events2 affected80 at risk
Oesophageal obstruction	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0002 events1 affected82 at risk EG0010 events0 affected80 at risk
Oesophageal stenosis	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected82 at risk EG0010 events0 affected80 at risk
Oesophagitis	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0002 events2 affected82 at risk EG0010 events0 affected80 at risk
Pancreatitis	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected82 at risk EG0010 events0 affected80 at risk
Small intestinal haemorrhage	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected82 at risk EG0011 events1 affected80 at risk
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected82 at risk EG0011 events1 affected80 at risk
Vomiting	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0004 events3 affected82 at risk EG0012 events2 affected80 at risk
Asthenia	General disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected82 at risk EG0010 events0 affected80 at risk
Death	General disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected82 at risk EG0012 events2 affected80 at risk
Device dislocation	General disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected82 at risk EG0012 events2 affected80 at risk
Disease progression	General disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected82 at risk EG0013 events3 affected80 at risk
Multi-organ failure	General disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected82 at risk EG0010 events0 affected80 at risk
Non-cardiac chest pain	General disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected82 at risk EG0011 events1 affected80 at risk
Pain	General disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected82 at risk EG0011 events1 affected80 at risk
Pyrexia	General disorders	MedDRA 12.0	Systematic Assessment	EG0003 events2 affected82 at risk EG0011 events1 affected80 at risk
Bile duct stone	Hepatobiliary disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected82 at risk EG0011 events1 affected80 at risk
Cholangitis	Hepatobiliary disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected82 at risk EG0011 events1 affected80 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected82 at risk EG0010 events0 affected80 at risk
Hepatic failure	Hepatobiliary disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected82 at risk EG0010 events0 affected80 at risk
Jaundice cholestatic	Hepatobiliary disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected82 at risk EG0011 events1 affected80 at risk
Anaphylactic reaction	Immune system disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected82 at risk EG0011 events1 affected80 at risk
Appendicitis	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected82 at risk EG0010 events0 affected80 at risk
Bacteraemia	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected82 at risk EG0012 events2 affected80 at risk
Catheter site infection	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected82 at risk EG0010 events0 affected80 at risk
Cellulitis	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected82 at risk EG0010 events0 affected80 at risk
Gastroenteritis	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected82 at risk EG0011 events1 affected80 at risk
Kidney infection	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected82 at risk EG0010 events0 affected80 at risk
Lung infection	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected82 at risk EG0010 events0 affected80 at risk
Perirectal abscess	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected82 at risk EG0011 events1 affected80 at risk
Peritonitis	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected82 at risk EG0010 events0 affected80 at risk
Pneumonia	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0003 events3 affected82 at risk EG0010 events0 affected80 at risk
Pyelonephritis	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected82 at risk EG0010 events0 affected80 at risk
Respiratory syncytial virus infection	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected82 at risk EG0010 events0 affected80 at risk
Sepsis	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0003 events3 affected82 at risk EG0013 events3 affected80 at risk
Urinary tract infection	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected82 at risk EG0011 events1 affected80 at risk
Anastomotic ulcer haemorrhage	Injury, poisoning and procedural complications	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected82 at risk EG0011 events1 affected80 at risk
Foot fracture	Injury, poisoning and procedural complications	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected82 at risk EG0010 events0 affected80 at risk
Laceration	Injury, poisoning and procedural complications	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected82 at risk EG0010 events0 affected80 at risk
Subdural haemorrhage	Injury, poisoning and procedural complications	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected82 at risk EG0011 events1 affected80 at risk
Urostomy complication	Injury, poisoning and procedural complications	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected82 at risk EG0011 events1 affected80 at risk
International normalised ratio increased	Investigations	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected82 at risk EG0011 events1 affected80 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 12.0	Systematic Assessment	EG0003 events3 affected82 at risk EG0011 events1 affected80 at risk
Failure to thrive	Metabolism and nutrition disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected82 at risk EG0011 events1 affected80 at risk
Hypophagia	Metabolism and nutrition disorders	MedDRA 12.0	Systematic Assessment	EG0002 events1 affected82 at risk EG0010 events0 affected80 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected82 at risk EG0010 events0 affected80 at risk
Polyarthritis	Musculoskeletal and connective tissue disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected82 at risk EG0010 events0 affected80 at risk
Malignant pleural effusion	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected82 at risk EG0011 events1 affected80 at risk
Meningioma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected82 at risk EG0010 events0 affected80 at risk
Metastases to central nervous system	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected82 at risk EG0011 events1 affected80 at risk
Oesophageal carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected82 at risk EG0011 events1 affected80 at risk
Depressed level of consciousness	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected82 at risk EG0010 events0 affected80 at risk
Headache	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG0003 events3 affected82 at risk EG0010 events0 affected80 at risk
Memory impairment	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected82 at risk EG0010 events0 affected80 at risk
Parkinsonism	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected82 at risk EG0011 events1 affected80 at risk
Syncope	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG0003 events3 affected82 at risk EG0011 events1 affected80 at risk
Confusional state	Psychiatric disorders	MedDRA 12.0	Systematic Assessment	EG0002 events2 affected82 at risk EG0011 events1 affected80 at risk
Hydronephrosis	Renal and urinary disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected82 at risk EG0010 events0 affected80 at risk
Renal failure acute	Renal and urinary disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected82 at risk EG0011 events1 affected80 at risk
Renal injury	Renal and urinary disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected82 at risk EG0010 events0 affected80 at risk
Urinary retention	Renal and urinary disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected82 at risk EG0011 events1 affected80 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected82 at risk EG0010 events0 affected80 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected82 at risk EG0010 events0 affected80 at risk
Atelectasis	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected82 at risk EG0011 events1 affected80 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG0003 events2 affected82 at risk EG0010 events0 affected80 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG0002 events2 affected82 at risk EG0012 events2 affected80 at risk
Emphysema	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected82 at risk EG0010 events0 affected80 at risk
Interstitial lung disease	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected82 at risk EG0010 events0 affected80 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected82 at risk EG0013 events3 affected80 at risk
Pneumonia aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG0003 events2 affected82 at risk EG0011 events1 affected80 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected82 at risk EG0010 events0 affected80 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG0002 events2 affected82 at risk EG0010 events0 affected80 at risk
Deep vein thrombosis	Vascular disorders	MedDRA 12.0	Systematic Assessment	EG0005 events5 affected82 at risk EG0011 events1 affected80 at risk
Embolism venous	Vascular disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected82 at risk EG0011 events1 affected80 at risk
Hypertension	Vascular disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected82 at risk EG0010 events0 affected80 at risk
Hypotension	Vascular disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected82 at risk EG0013 events3 affected80 at risk
Superior vena cava syndrome	Vascular disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected82 at risk EG0011 events1 affected80 at risk
Thrombosis	Vascular disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected82 at risk EG0011 events1 affected80 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 12.0	Systematic Assessment	EG00041 events29 affected82 at risk EG00158 events38 affected80 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA 12.0	Systematic Assessment	EG00018 events7 affected82 at risk EG00114 events9 affected80 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 12.0	Systematic Assessment	EG00076 events29 affected82 at risk EG001108 events33 affected80 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 12.0	Systematic Assessment	EG00062 events30 affected82 at risk EG00145 events20 affected80 at risk
Vision blurred	Eye disorders	MedDRA 12.0	Systematic Assessment	EG0003 events3 affected82 at risk EG0017 events6 affected80 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0009 events8 affected82 at risk EG0015 events5 affected80 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG00020 events17 affected82 at risk EG00120 events14 affected80 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG00010 events8 affected82 at risk EG00111 events8 affected80 at risk
Ascites	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0008 events5 affected82 at risk EG0012 events2 affected80 at risk
Constipation	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG00041 events36 affected82 at risk EG00141 events32 affected80 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG00067 events36 affected82 at risk EG00156 events33 affected80 at risk
Dry mouth	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0006 events6 affected82 at risk EG0015 events4 affected80 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0009 events7 affected82 at risk EG0018 events8 affected80 at risk
Dysphagia	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG00015 events10 affected82 at risk EG00118 events13 affected80 at risk
Flatulence	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0003 events3 affected82 at risk EG0015 events5 affected80 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0009 events6 affected82 at risk EG00111 events5 affected80 at risk
Nausea	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG00072 events52 affected82 at risk EG00182 events56 affected80 at risk
Oral pain	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0006 events5 affected82 at risk EG0014 events4 affected80 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG00016 events10 affected82 at risk EG00121 events16 affected80 at risk
Vomiting	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG00049 events32 affected82 at risk EG00142 events28 affected80 at risk
Asthenia	General disorders	MedDRA 12.0	Systematic Assessment	EG00013 events12 affected82 at risk EG00113 events8 affected80 at risk
Chest pain	General disorders	MedDRA 12.0	Systematic Assessment	EG0002 events2 affected82 at risk EG00111 events7 affected80 at risk
Chills	General disorders	MedDRA 12.0	Systematic Assessment	EG0005 events5 affected82 at risk EG0012 events2 affected80 at risk
Fatigue	General disorders	MedDRA 12.0	Systematic Assessment	EG00091 events57 affected82 at risk EG00181 events56 affected80 at risk
Mucosal inflammation	General disorders	MedDRA 12.0	Systematic Assessment	EG00023 events17 affected82 at risk EG00113 events9 affected80 at risk
Oedema peripheral	General disorders	MedDRA 12.0	Systematic Assessment	EG00030 events20 affected82 at risk EG00119 events14 affected80 at risk
Pyrexia	General disorders	MedDRA 12.0	Systematic Assessment	EG00012 events9 affected82 at risk EG00111 events11 affected80 at risk
Temperature intolerance	General disorders	MedDRA 12.0	Systematic Assessment	EG0008 events8 affected82 at risk EG00117 events14 affected80 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0006 events6 affected82 at risk EG0016 events5 affected80 at risk
Urinary tract infection	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG00011 events11 affected82 at risk EG00112 events9 affected80 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA 12.0	Systematic Assessment	EG0003 events3 affected82 at risk EG0015 events5 affected80 at risk
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA 12.0	Systematic Assessment	EG00014 events7 affected82 at risk EG0017 events5 affected80 at risk
Alanine aminotransferase increased	Investigations	MedDRA 12.0	Systematic Assessment	EG0006 events5 affected82 at risk EG0019 events7 affected80 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 12.0	Systematic Assessment	EG00010 events7 affected82 at risk EG00118 events11 affected80 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA 12.0	Systematic Assessment	EG0007 events6 affected82 at risk EG00124 events15 affected80 at risk
Blood creatinine increased	Investigations	MedDRA 12.0	Systematic Assessment	EG00011 events5 affected82 at risk EG0011 events1 affected80 at risk
Neutrophil count decreased	Investigations	MedDRA 12.0	Systematic Assessment	EG00050 events16 affected82 at risk EG00116 events9 affected80 at risk
Platelet count decreased	Investigations	MedDRA 12.0	Systematic Assessment	EG00045 events19 affected82 at risk EG00124 events12 affected80 at risk
Weight decreased	Investigations	MedDRA 12.0	Systematic Assessment	EG00041 events28 affected82 at risk EG00131 events21 affected80 at risk
White blood cell count decreased	Investigations	MedDRA 12.0	Systematic Assessment	EG0008 events5 affected82 at risk EG0018 events6 affected80 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 12.0	Systematic Assessment	EG00047 events37 affected82 at risk EG00136 events22 affected80 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 12.0	Systematic Assessment	EG00028 events21 affected82 at risk EG00114 events12 affected80 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 12.0	Systematic Assessment	EG00015 events9 affected82 at risk EG00122 events10 affected80 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA 12.0	Systematic Assessment	EG0007 events5 affected82 at risk EG0018 events4 affected80 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA 12.0	Systematic Assessment	EG00015 events9 affected82 at risk EG0019 events4 affected80 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 12.0	Systematic Assessment	EG00023 events16 affected82 at risk EG00113 events8 affected80 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 12.0	Systematic Assessment	EG0003 events3 affected82 at risk EG0015 events5 affected80 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 12.0	Systematic Assessment	EG0007 events3 affected82 at risk EG0018 events6 affected80 at risk
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA 12.0	Systematic Assessment	EG00013 events6 affected82 at risk EG0014 events1 affected80 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 12.0	Systematic Assessment	EG0004 events2 affected82 at risk EG0019 events8 affected80 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 12.0	Systematic Assessment	EG00012 events10 affected82 at risk EG00119 events11 affected80 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 12.0	Systematic Assessment	EG0007 events7 affected82 at risk EG0017 events7 affected80 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 12.0	Systematic Assessment	EG00014 events8 affected82 at risk EG0015 events5 affected80 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected82 at risk EG0018 events6 affected80 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 12.0	Systematic Assessment	EG0009 events9 affected82 at risk EG0019 events7 affected80 at risk
Pain in jaw	Musculoskeletal and connective tissue disorders	MedDRA 12.0	Systematic Assessment	EG0006 events6 affected82 at risk EG0012 events2 affected80 at risk
Dizziness	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG00022 events19 affected82 at risk EG00115 events12 affected80 at risk
Dysgeusia	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG00014 events13 affected82 at risk EG00115 events14 affected80 at risk
Headache	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG00024 events18 affected82 at risk EG00116 events12 affected80 at risk
Memory impairment	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG0005 events5 affected82 at risk EG0010 events0 affected80 at risk
Paraesthesia	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG00010 events8 affected82 at risk EG00133 events20 affected80 at risk
Peripheral motor neuropathy	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG0003 events3 affected82 at risk EG0018 events6 affected80 at risk
Peripheral sensory neuropathy	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG00068 events44 affected82 at risk EG00173 events43 affected80 at risk
Anxiety	Psychiatric disorders	MedDRA 12.0	Systematic Assessment	EG0004 events4 affected82 at risk EG0018 events8 affected80 at risk
Depression	Psychiatric disorders	MedDRA 12.0	Systematic Assessment	EG0007 events7 affected82 at risk EG0015 events4 affected80 at risk
Insomnia	Psychiatric disorders	MedDRA 12.0	Systematic Assessment	EG00015 events15 affected82 at risk EG00124 events20 affected80 at risk
Dysuria	Renal and urinary disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected82 at risk EG0015 events5 affected80 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG00021 events19 affected82 at risk EG00118 events15 affected80 at risk
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG0008 events8 affected82 at risk EG0012 events1 affected80 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG00023 events16 affected82 at risk EG00124 events16 affected80 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG00028 events24 affected82 at risk EG0019 events9 affected80 at risk
Hiccups	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG0002 events2 affected82 at risk EG0017 events6 affected80 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG0005 events5 affected82 at risk EG0012 events2 affected80 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 12.0	Systematic Assessment	EG00010 events9 affected82 at risk EG00110 events8 affected80 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 12.0	Systematic Assessment	EG0003 events3 affected82 at risk EG0019 events9 affected80 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 12.0	Systematic Assessment	EG0006 events3 affected82 at risk EG0018 events6 affected80 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 12.0	Systematic Assessment	EG0004 events4 affected82 at risk EG0016 events5 affected80 at risk
Hypertension	Vascular disorders	MedDRA 12.0	Systematic Assessment	EG00041 events30 affected82 at risk EG00110 events10 affected80 at risk
Hypotension	Vascular disorders	MedDRA 12.0	Systematic Assessment	EG00010 events7 affected82 at risk EG00114 events7 affected80 at risk

ID	Term
D013274	Stomach Neoplasms
D004938	Esophageal Neoplasms
D009369	Neoplasms

ID	Term
D005770	Gastrointestinal Neoplasms
D004067	Digestive System Neoplasms
D009371	Neoplasms by Site
D004066	Digestive System Diseases
D005767	Gastrointestinal Diseases
D013272	Stomach Diseases
D006258	Head and Neck Neoplasms
D004935	Esophageal 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
D056831	Coordination Complexes
D009930	Organic Chemicals
D005575	Formyltetrahydrofolates
D013763	Tetrahydrofolates
D005492	Folic Acid
D011622	Pterins
D011621	Pteridines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds
D003067	Coenzymes
D045762	Enzymes and Coenzymes
D014498	Uracil
D011744	Pyrimidinones
D011743	Pyrimidines
D006573	Heterocyclic Compounds, 1-Ring

ID	Title	Description
BG000	Ramucirumab and mFOLFOX6	Ramucirumab: 8 mg/kg intravenous infusion administered on Day 1 of each cycle (14 days/cycle). In Cycles 1 and 2, there was a 1-hour observation prior to administering mFOLFOX6. mFOLFOX6: Administered intravenously per manufacturer's instructions for each drug substance on Day 1 of each cycle (14 days/cycle). Oxaliplatin: 85 mg/m^2 Leucovorin: 400 mg/m^2 5-FU: 400 mg/m^2 bolus 5-FU: 2400 mg/m^2 continuous given over 46-48 hours Participants received study treatment every 2 weeks until disease progression, unacceptable toxicity, or another withdrawal criterion was met.
BG001	Placebo and mFOLFOX6	Placebo: intravenous infusion administered on Day 1 of each cycle (14 days/cycle). In Cycles 1 and 2, there was a 1-hour observation prior to administering mFOLFOX6. mFOLFOX6: Administered intravenously per manufacturer's instructions for each drug substance on Day 1 of each cycle (14 days/cycle). Oxaliplatin: 85 mg/m^2 Leucovorin: 400 mg/m^2 5-FU: 400 mg/m^2 bolus 5-FU: 2400 mg/m^2 continuous given over 46-48 hours Participants received study treatment every 2 weeks until disease progression, unacceptable toxicity, or another withdrawal criterion was met.
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	Ramucirumab and mFOLFOX6	Ramucirumab: 8 mg/kg intravenous infusion administered on Day 1 of each cycle (14 days/cycle). In Cycles 1 and 2, there was a 1-hour observation prior to administering mFOLFOX6. mFOLFOX6: Administered intravenously per manufacturer's instructions for each drug substance on Day 1 of each cycle (14 days/cycle). Oxaliplatin: 85 mg/m^2 Leucovorin: 400 mg/m^2 5-FU: 400 mg/m^2 bolus 5-FU: 2400 mg/m^2 continuous given over 46-48 hours Participants received study treatment every 2 weeks until disease progression, unacceptable toxicity, or another withdrawal criterion was met.			48	82	82	82
EG001	Placebo and mFOLFOX6	Placebo: intravenous infusion administered on Day 1 of each cycle (14 days/cycle). In Cycles 1 and 2, there was a 1-hour observation prior to administering mFOLFOX6. mFOLFOX6: Administered intravenously per manufacturer's instructions for each drug substance on Day 1 of each cycle (14 days/cycle). Oxaliplatin: 85 mg/m^2 Leucovorin: 400 mg/m^2 5-FU: 400 mg/m^2 bolus 5-FU: 2400 mg/m^2 continuous given over 46-48 hours Participants received study treatment every 2 weeks until disease progression, unacceptable toxicity, or another withdrawal criterion was met.			32	80	79	80

ID	Term
D000096662	Ramucirumab
D000077150	Oxaliplatin
D002955	Leucovorin
D005472	Fluorouracil