A Study of Herceptin (Trastuzumab) in Combination With Ci... | NCT01450696

NCT01450696

ID	Type	Description	Link
2011-001526-19	EudraCT Number

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Capecitabine + Cisplatin + Herceptin (6 mg/kg)	Active Comparator	Participants will receive Herceptin at a loading dose of 8 mg/kg on Day 1 of Cycle 1 followed by 6 mg/kg q3w as a standard of care from Day 1 of Cycle 2 until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason (cycle length = 21 days). Participants will also receive cisplatin 80 mg/m^2 intravenously q3w plus capecitabine 800 mg/m^2 orally twice daily for 14 days q3w for up to 6 treatment cycles (Cycles 1 to 6).	Drug: Capecitabine Drug: Cisplatin Drug: Herceptin
Capecitabine + Cisplatin + Herceptin (10 mg/kg)	Experimental	Participants will receive Herceptin at a loading dose of 8 mg/kg on Day 1 of Cycle 1 followed by 10 mg/kg q3w from Day 1 of Cycle 2 until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason (cycle length = 21 days). Participants will also receive cisplatin 80 mg/m^2 intravenously q3w plus capecitabine 800 mg/m^2 orally twice daily for 14 days q3w for up to 6 treatment cycles (Cycles 1 to 6).	Drug: Capecitabine Drug: Cisplatin Drug: Herceptin

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Capecitabine	Drug	Capecitabine will be administered at a dose of 800 mg/m^2 orally twice daily for 14 days q3w for up to 6 cycles (Cycles 1 to 6).	Capecitabine + Cisplatin + Herceptin (10 mg/kg)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percentage of Participants Who Died - FAS	The percentage of participants who died as of the analysis data cutoff date of 13 February 2015 was reported among participants from the FAS with available data.	From date of randomization until death or premature withdrawal (up to approximately 31 months or data cutoff date of 13 February 2015)
Overall Survival - FAS	Overall survival was defined as the time from the date of randomization to the date of death from any cause. Overall survival was estimated among participants from the FAS using the Kaplan-Meier approach. The 95 percent (%) confidence interval (CI) for median was computed using the method of Brookmeyer and Crowley.	From date of randomization until death or premature withdrawal (up to approximately 31 months or data cutoff date of 13 February 2015)

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Participants Who Died - Per Protocol Set (PPS)	The percentage of participants who died as of the analysis data cutoff date of 13 February 2015 was reported among participants from the PPS.	From date of randomization until death or premature withdrawal (up to approximately 31 months or data cutoff date of 13 February 2015)

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Histologically confirmed adenocarcinoma of the stomach or gastro-esophageal junction with metastatic disease documented to involve at least liver or lung or both
Measurable disease according to RECIST Version 1.1 or non-measurable evaluable disease
At least 2 organs involved in metastatic gastric tumor (including at least lung or liver or both) in addition to the site of primary tumor, where metastasis in distant lymph nodes, peritoneal metastasis, and malignant pleural effusion may count as "organs" in this context
HER2-positive primary or metastatic tumor as assessed by central laboratory
Adequate renal function (creatinine clearance greater than equal to (≥) 45 milliliters per minute [mL/min])
Eastern Cooperative Oncology Group (ECOG) performance status of 2

Exclusion Criteria:

Previous chemotherapy for locally advanced or metastatic disease
Prior gastrectomy (partial or total) for the underlying malignant disease under investigation
Prior therapy with an anti-HER2 agent and/or platinum-based chemotherapeutic agent
Residual relevant toxicity resulting from previous therapy
Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome (such as jejunostomy probe and gastric or jejunostomy tubes) which may impair the ability to administer or absorb capecitabine
Current (significant or uncontrolled) gastrointestinal bleeding
Other malignancy within the last 5 years, except for carcinoma in situ of the cervix and basal or squamous cell carcinoma of the skin
History of documented congestive heart failure, angina pectoris requiring medication, electrocardiogram (ECG) evidence of transmural myocardial infraction, poorly controlled hypertension, clinically significant valvular heart disease, or high-risk uncontrollable arrhythmias
Baseline left ventricular ejection fraction (LVEF) less than (<) 50%, documented by echocardiography, multiple-gated radionuclide angiography (MUGA) scan, or cardiac magnetic resonance imaging (MRI)
Chronic or high-dose corticosteroid therapy
History or clinical evidence of brain metastases
Pregnant women
Active infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C, or HIV-seropositive

Name	Affiliation	Role
Clinical Trials	Hoffmann-La Roche	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
		La Jolla	California	92093	United States

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Capecitabine + Cisplatin + Herceptin (6 mg/kg)	Participants received Herceptin at a loading dose of 8 milligrams per kilogram (mg/kg) on Day 1 of Cycle 1 followed by 6 mg/kg every three weeks (q3w) as standard of care from Day 1 of Cycle 2 until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason (cycle length = 21 days). Participants also received cisplatin 80 milligrams per meter-squared (mg/m^2) intravenously q3w plus capecitabine 800 mg/m^2 orally twice daily for 14 days q3w for up to 6 treatment cycles (Cycles 1 to 6).

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Capecitabine + Cisplatin + Herceptin (6 mg/kg)	Participants received Herceptin at a loading dose of 8 mg/kg on Day 1 of Cycle 1 followed by 6 mg/kg q3w as standard of care from Day 1 of Cycle 2 until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason (cycle length = 21 days). Participants also received cisplatin 80 mg/m^2 intravenously q3w plus capecitabine 800 mg/m^2 orally twice daily for 14 days q3w for up to 6 treatment cycles (Cycles 1 to 6).
BG001	Capecitabine + Cisplatin + Herceptin (10 mg/kg)	Participants received Herceptin at a loading dose of 8 mg/kg on Day 1 of Cycle 1 followed by 10 mg/kg q3w from Day 1 of Cycle 2 until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason (cycle length = 21 days). Participants also received cisplatin 80 mg/m^2 intravenously q3w plus capecitabine 800 mg/m^2 orally twice daily for 14 days q3w for up to 6 treatment cycles (Cycles 1 to 6).
BG002	Total	Total of all reporting groups

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

Percentage of Participants Who Died - FAS

The percentage of participants who died as of the analysis data cutoff date of 13 February 2015 was reported among participants from the FAS with available data.

FAS population. Here, number of participants analyzed reflects the number of participants who were evaluable for this outcome measure.

Posted

Number

percentage of participants

From date of randomization until death or premature withdrawal (up to approximately 31 months or data cutoff date of 13 February 2015)

ID	Title	Description
OG000	Capecitabine + Cisplatin + Herceptin (6 mg/kg)	Participants received Herceptin at a loading dose of 8 mg/kg on Day 1 of Cycle 1 followed by 6 mg/kg q3w as standard of care from Day 1 of Cycle 2 until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason (cycle length = 21 days). Participants also received cisplatin 80 mg/m^2 intravenously q3w plus capecitabine 800 mg/m^2 orally twice daily for 14 days q3w for up to 6 treatment cycles (Cycles 1 to 6).
OG001	Capecitabine + Cisplatin + Herceptin (10 mg/kg)	Participants received Herceptin at a loading dose of 8 mg/kg on Day 1 of Cycle 1 followed by 10 mg/kg q3w from Day 1 of Cycle 2 until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason (cycle length = 21 days). Participants also received cisplatin 80 mg/m^2 intravenously q3w plus capecitabine 800 mg/m^2 orally twice daily for 14 days q3w for up to 6 treatment cycles (Cycles 1 to 6).

Units	Counts
Participants	OG000124 OG001124

Title

Denominators

Categories

Title	Measurements
	OG00046.8 OG00154.0

Primary

Overall Survival - FAS

Overall survival was defined as the time from the date of randomization to the date of death from any cause. Overall survival was estimated among participants from the FAS using the Kaplan-Meier approach. The 95 percent (%) confidence interval (CI) for median was computed using the method of Brookmeyer and Crowley.

FAS population. Here, number of participants analyzed reflects the number of participants who were evaluable for this outcome measure.

Posted

Median

95% Confidence Interval

months

From date of randomization until death or premature withdrawal (up to approximately 31 months or data cutoff date of 13 February 2015)

ID	Title	Description
OG000	Capecitabine + Cisplatin + Herceptin (6 mg/kg)	Participants received Herceptin at a loading dose of 8 mg/kg on Day 1 of Cycle 1 followed by 6 mg/kg q3w as standard of care from Day 1 of Cycle 2 until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason (cycle length = 21 days). Participants also received cisplatin 80 mg/m^2 intravenously q3w plus capecitabine 800 mg/m^2 orally twice daily for 14 days q3w for up to 6 treatment cycles (Cycles 1 to 6).
OG001	Capecitabine + Cisplatin + Herceptin (10 mg/kg)	Participants received Herceptin at a loading dose of 8 mg/kg on Day 1 of Cycle 1 followed by 10 mg/kg q3w from Day 1 of Cycle 2 until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason (cycle length = 21 days). Participants also received cisplatin 80 mg/m^2 intravenously q3w plus capecitabine 800 mg/m^2 orally twice daily for 14 days q3w for up to 6 treatment cycles (Cycles 1 to 6).

Secondary

Percentage of Participants Who Died - Per Protocol Set (PPS)

The percentage of participants who died as of the analysis data cutoff date of 13 February 2015 was reported among participants from the PPS.

The PPS included all participants who were found to have a trastuzumab minimum plasma concentration (Cmin) less than (<) 12 micrograms per milliliter (μg/mL) on treatment Day 21 of Cycle 1 following the initial loading dose of 8 mg/kg.

Posted

Number

percentage of participants

From date of randomization until death or premature withdrawal (up to approximately 31 months or data cutoff date of 13 February 2015)

ID	Title	Description
OG000	Capecitabine + Cisplatin + Herceptin (6 mg/kg)	Participants received Herceptin at a loading dose of 8 mg/kg on Day 1 of Cycle 1 followed by 6 mg/kg q3w as standard of care from Day 1 of Cycle 2 until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason (cycle length = 21 days). Participants also received cisplatin 80 mg/m^2 intravenously q3w plus capecitabine 800 mg/m^2 orally twice daily for 14 days q3w for up to 6 treatment cycles (Cycles 1 to 6).
OG001	Capecitabine + Cisplatin + Herceptin (10 mg/kg)	Participants received Herceptin at a loading dose of 8 mg/kg on Day 1 of Cycle 1 followed by 10 mg/kg q3w from Day 1 of Cycle 2 until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason (cycle length = 21 days). Participants also received cisplatin 80 mg/m^2 intravenously q3w plus capecitabine 800 mg/m^2 orally twice daily for 14 days q3w for up to 6 treatment cycles (Cycles 1 to 6).

Secondary

Overall Survival - PPS

Overall survival was defined as the time from the date of randomization to the date of death from any cause. Overall survival was estimated among participants from the PPS using the Kaplan-Meier approach. The 95% CI for median was computed using the method of Brookmeyer and Crowley.

PPS population.

Posted

Median

95% Confidence Interval

months

From date of randomization until death or premature withdrawal (up to approximately 31 months or data cutoff date of 13 February 2015)

ID	Title	Description
OG000	Capecitabine + Cisplatin + Herceptin (6 mg/kg)	Participants received Herceptin at a loading dose of 8 mg/kg on Day 1 of Cycle 1 followed by 6 mg/kg q3w as standard of care from Day 1 of Cycle 2 until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason (cycle length = 21 days). Participants also received cisplatin 80 mg/m^2 intravenously q3w plus capecitabine 800 mg/m^2 orally twice daily for 14 days q3w for up to 6 treatment cycles (Cycles 1 to 6).
OG001	Capecitabine + Cisplatin + Herceptin (10 mg/kg)	Participants received Herceptin at a loading dose of 8 mg/kg on Day 1 of Cycle 1 followed by 10 mg/kg q3w from Day 1 of Cycle 2 until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason (cycle length = 21 days). Participants also received cisplatin 80 mg/m^2 intravenously q3w plus capecitabine 800 mg/m^2 orally twice daily for 14 days q3w for up to 6 treatment cycles (Cycles 1 to 6).

Secondary

Percentage of Participants With Disease Progression or Death - PPS

Disease progression was defined by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as a ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including Baseline (nadir). In addition to the relative increase of 20%, the sum was also required to demonstrate an absolute increase of ≥5 millimeters (mm). The percentage of participants who died or experienced disease progression as of the analysis data cutoff date of 13 February 2015 was reported among participants from the PPS.

PPS population.

Posted

Number

percentage of participants

From date of randomization until first occurrence of disease progression or death; assessed every 6 weeks (up to approximately 31 months or data cutoff date of 13 February 2015)

ID	Title	Description
OG000	Capecitabine + Cisplatin + Herceptin (6 mg/kg)	Participants received Herceptin at a loading dose of 8 mg/kg on Day 1 of Cycle 1 followed by 6 mg/kg q3w as standard of care from Day 1 of Cycle 2 until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason (cycle length = 21 days). Participants also received cisplatin 80 mg/m^2 intravenously q3w plus capecitabine 800 mg/m^2 orally twice daily for 14 days q3w for up to 6 treatment cycles (Cycles 1 to 6).
OG001	Capecitabine + Cisplatin + Herceptin (10 mg/kg)	Participants received Herceptin at a loading dose of 8 mg/kg on Day 1 of Cycle 1 followed by 10 mg/kg q3w from Day 1 of Cycle 2 until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason (cycle length = 21 days). Participants also received cisplatin 80 mg/m^2 intravenously q3w plus capecitabine 800 mg/m^2 orally twice daily for 14 days q3w for up to 6 treatment cycles (Cycles 1 to 6).

Secondary

Progression-Free Survival - PPS

Progression-free survival was defined as the time between the day of randomization and the date of first documentation of disease progression or date of death, whichever occurred first, measured following RECIST Version 1.1 criteria. Disease progression was defined as a ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including Baseline (nadir). In addition to the relative increase of 20%, the sum was also required to demonstrate an absolute increase of ≥5 mm. The 95% CI for median was computed using the method of Brookmeyer and Crowley.

PPS population.

Posted

Median

95% Confidence Interval

months

From date of randomization until first occurrence of disease progression or death; assessed every 6 weeks (up to approximately 31 months or data cutoff date of 13 February 2015)

ID	Title	Description
OG000	Capecitabine + Cisplatin + Herceptin (6 mg/kg)	Participants received Herceptin at a loading dose of 8 mg/kg on Day 1 of Cycle 1 followed by 6 mg/kg q3w as standard of care from Day 1 of Cycle 2 until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason (cycle length = 21 days). Participants also received cisplatin 80 mg/m^2 intravenously q3w plus capecitabine 800 mg/m^2 orally twice daily for 14 days q3w for up to 6 treatment cycles (Cycles 1 to 6).
OG001	Capecitabine + Cisplatin + Herceptin (10 mg/kg)

Secondary

Percentage of Participants With Objective Response - PPS

Objective response was defined as the occurrence of either a complete response (CR) or partial response (PR) as determined by RECIST Version 1.1 based on investigator assessment. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) were required to have reduction in short axis to <10 mm. PR was defined as a ≥30% decrease in the sum of diameters of target lesions, taking as reference the Baseline sum diameters. The 95% CI was constructed using Blyth-Still-Casella method.

PPS population.

Posted

Number

95% Confidence Interval

percentage of participants

From date of randomization until first occurrence of disease progression or death; assessed every 6 weeks (up to approximately 31 months or data cutoff date of 13 February 2015)

ID	Title	Description
OG000	Capecitabine + Cisplatin + Herceptin (6 mg/kg)	Participants received Herceptin at a loading dose of 8 mg/kg on Day 1 of Cycle 1 followed by 6 mg/kg q3w as standard of care from Day 1 of Cycle 2 until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason (cycle length = 21 days). Participants also received cisplatin 80 mg/m^2 intravenously q3w plus capecitabine 800 mg/m^2 orally twice daily for 14 days q3w for up to 6 treatment cycles (Cycles 1 to 6).
OG001	Capecitabine + Cisplatin + Herceptin (10 mg/kg)	Participants received Herceptin at a loading dose of 8 mg/kg on Day 1 of Cycle 1 followed by 10 mg/kg q3w from Day 1 of Cycle 2 until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason (cycle length = 21 days). Participants also received cisplatin 80 mg/m^2 intravenously q3w plus capecitabine 800 mg/m^2 orally twice daily for 14 days q3w for up to 6 treatment cycles (Cycles 1 to 6).

Secondary

Trastuzumab Cmin on Day 21 of Cycles 1 to 11 - FAS

Cmin samples were obtained in all participants randomized to receive Herceptin (FAS). The observed Cmin was recorded, averaged among all participants, and expressed in μg/mL.

FAS population. Here, number of participants analyzed reflects the number of participants who were evaluable for this outcome measure. Here also, "n" reflects the number of participants who were evaluable for each category in the respective arms.

Posted

Mean

Standard Deviation

μg/mL

Day 21 of Cycle 1, 2, 3, 4, 5, 7, 9, 11 (cycle length = 21 days)

ID	Title	Description
OG000	Capecitabine + Cisplatin + Herceptin (6 mg/kg)	Participants received Herceptin at a loading dose of 8 mg/kg on Day 1 of Cycle 1 followed by 6 mg/kg q3w as standard of care from Day 1 of Cycle 2 until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason (cycle length = 21 days). Participants also received cisplatin 80 mg/m^2 intravenously q3w plus capecitabine 800 mg/m^2 orally twice daily for 14 days q3w for up to 6 treatment cycles (Cycles 1 to 6).
OG001	Capecitabine + Cisplatin + Herceptin (10 mg/kg)	Participants received Herceptin at a loading dose of 8 mg/kg on Day 1 of Cycle 1 followed by 10 mg/kg q3w from Day 1 of Cycle 2 until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason (cycle length = 21 days). Participants also received cisplatin 80 mg/m^2 intravenously q3w plus capecitabine 800 mg/m^2 orally twice daily for 14 days q3w for up to 6 treatment cycles (Cycles 1 to 6).

Secondary

Trastuzumab Serum Concentration on Day 1 of Cycle 1 - FAS

Trastuzumab serum concentration samples were obtained in all participants randomized to receive Herceptin (FAS). The observed concentration values were recorded, averaged among all participants, and expressed in μg/mL.

Posted

Mean

Standard Deviation

μg/mL

Pre-dose (0 minutes) and within 15 minutes after end of 2-hour Herceptin infusion on Day 1 of Cycle 1 (cycle length = 21 days)

ID	Title	Description
OG000	Capecitabine + Cisplatin + Herceptin (6 mg/kg)	Participants received Herceptin at a loading dose of 8 mg/kg on Day 1 of Cycle 1 followed by 6 mg/kg q3w as standard of care from Day 1 of Cycle 2 until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason (cycle length = 21 days). Participants also received cisplatin 80 mg/m^2 intravenously q3w plus capecitabine 800 mg/m^2 orally twice daily for 14 days q3w for up to 6 treatment cycles (Cycles 1 to 6).
OG001	Capecitabine + Cisplatin + Herceptin (10 mg/kg)	Participants received Herceptin at a loading dose of 8 mg/kg on Day 1 of Cycle 1 followed by 10 mg/kg q3w from Day 1 of Cycle 2 until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason (cycle length = 21 days). Participants also received cisplatin 80 mg/m^2 intravenously q3w plus capecitabine 800 mg/m^2 orally twice daily for 14 days q3w for up to 6 treatment cycles (Cycles 1 to 6).

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Capecitabine + Cisplatin + Herceptin (6 mg/kg)	Participants received Herceptin at a loading dose of 8 mg/kg on Day 1 of Cycle 1 followed by 6 mg/kg q3w as standard of care from Day 1 of Cycle 2 until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason (cycle length = 21 days). Participants also received cisplatin 80 mg/m^2 intravenously q3w plus capecitabine 800 mg/m^2 orally twice daily for 14 days q3w for up to 6 treatment cycles (Cycles 1 to 6).			35	147	123	147
EG001	Capecitabine + Cisplatin + Herceptin (10 mg/kg)	Participants received Herceptin at a loading dose of 8 mg/kg on Day 1 of Cycle 1 followed by 10 mg/kg q3w from Day 1 of Cycle 2 until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason (cycle length = 21 days). Participants also received cisplatin 80 mg/m^2 intravenously q3w plus capecitabine 800 mg/m^2 orally twice daily for 14 days q3w for up to 6 treatment cycles (Cycles 1 to 6).			38	147	122	147

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anemia	Blood and lymphatic system disorders	MedDRA (18.0)	Non-systematic Assessment	EG0007 affected147 at risk EG0016 affected147 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA (18.0)	Non-systematic Assessment	EG0003 affected147 at risk EG0013 affected147 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 affected147 at risk EG0010 affected147 at risk
Pancytopenia	Blood and lymphatic system disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 affected147 at risk EG0011 affected147 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 affected147 at risk EG0011 affected147 at risk
Bradycardia	Cardiac disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 affected147 at risk EG0011 affected147 at risk
Cardiac arrest	Cardiac disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 affected147 at risk EG0011 affected147 at risk
Cardiovascular insufficiency	Cardiac disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 affected147 at risk EG0010 affected147 at risk
Myocardial infarction	Cardiac disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 affected147 at risk EG0011 affected147 at risk
Palpitations	Cardiac disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 affected147 at risk EG0011 affected147 at risk
Tachyarrhythmia	Cardiac disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 affected147 at risk EG0010 affected147 at risk
Ventricular fibrillation	Cardiac disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 affected147 at risk EG0011 affected147 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 affected147 at risk EG0010 affected147 at risk
Constipation	Gastrointestinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 affected147 at risk EG0010 affected147 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 affected147 at risk EG0014 affected147 at risk
Gastric haemorrhage	Gastrointestinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0002 affected147 at risk EG0010 affected147 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 affected147 at risk EG0010 affected147 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 affected147 at risk EG0010 affected147 at risk
Nausea	Gastrointestinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0002 affected147 at risk EG0010 affected147 at risk
Obstruction gastric	Gastrointestinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0002 affected147 at risk EG0011 affected147 at risk
Odynophagia	Gastrointestinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 affected147 at risk EG0011 affected147 at risk
Oesophageal haemorrhage	Gastrointestinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 affected147 at risk EG0011 affected147 at risk
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 affected147 at risk EG0011 affected147 at risk
Vomiting	Gastrointestinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0005 affected147 at risk EG0013 affected147 at risk
Asthenia	General disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 affected147 at risk EG0010 affected147 at risk
Death	General disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 affected147 at risk EG0011 affected147 at risk
Pyrexia	General disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 affected147 at risk EG0010 affected147 at risk
Drug-induced liver injury	Hepatobiliary disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 affected147 at risk EG0011 affected147 at risk
Appendicitis	Infections and infestations	MedDRA (18.0)	Non-systematic Assessment	EG0000 affected147 at risk EG0011 affected147 at risk
Catheter site infection	Infections and infestations	MedDRA (18.0)	Non-systematic Assessment	EG0000 affected147 at risk EG0011 affected147 at risk
Cellulitis	Infections and infestations	MedDRA (18.0)	Non-systematic Assessment	EG0000 affected147 at risk EG0011 affected147 at risk
Infective spondylitis	Infections and infestations	MedDRA (18.0)	Non-systematic Assessment	EG0000 affected147 at risk EG0011 affected147 at risk
Neutropenic sepsis	Infections and infestations	MedDRA (18.0)	Non-systematic Assessment	EG0000 affected147 at risk EG0011 affected147 at risk
Pneumonia	Infections and infestations	MedDRA (18.0)	Non-systematic Assessment	EG0002 affected147 at risk EG0012 affected147 at risk
Sepsis	Infections and infestations	MedDRA (18.0)	Non-systematic Assessment	EG0002 affected147 at risk EG0011 affected147 at risk
Tinea pedis	Infections and infestations	MedDRA (18.0)	Non-systematic Assessment	EG0000 affected147 at risk EG0011 affected147 at risk
Tooth infection	Infections and infestations	MedDRA (18.0)	Non-systematic Assessment	EG0001 affected147 at risk EG0010 affected147 at risk
Urinary tract infection	Infections and infestations	MedDRA (18.0)	Non-systematic Assessment	EG0001 affected147 at risk EG0010 affected147 at risk
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA (18.0)	Non-systematic Assessment	EG0000 affected147 at risk EG0011 affected147 at risk
Lymphatic duct injury	Injury, poisoning and procedural complications	MedDRA (18.0)	Non-systematic Assessment	EG0001 affected147 at risk EG0010 affected147 at risk
Spinal compression fracture	Injury, poisoning and procedural complications	MedDRA (18.0)	Non-systematic Assessment	EG0001 affected147 at risk EG0010 affected147 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA (18.0)	Non-systematic Assessment	EG0002 affected147 at risk EG0010 affected147 at risk
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 affected147 at risk EG0011 affected147 at risk
Electrolyte imbalance	Metabolism and nutrition disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 affected147 at risk EG0010 affected147 at risk
Hypernatraemia	Metabolism and nutrition disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 affected147 at risk EG0010 affected147 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 affected147 at risk EG0011 affected147 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 affected147 at risk EG0011 affected147 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 affected147 at risk EG0011 affected147 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (18.0)	Non-systematic Assessment	EG0002 affected147 at risk EG0011 affected147 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 affected147 at risk EG0011 affected147 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 affected147 at risk EG0011 affected147 at risk
Cerebral ischaemia	Nervous system disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 affected147 at risk EG0011 affected147 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 affected147 at risk EG0010 affected147 at risk
Dizziness	Nervous system disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 affected147 at risk EG0011 affected147 at risk
Haemorrhage intracranial	Nervous system disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 affected147 at risk EG0010 affected147 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA (18.0)	Non-systematic Assessment	EG0004 affected147 at risk EG0012 affected147 at risk
Renal failure	Renal and urinary disorders	MedDRA (18.0)	Non-systematic Assessment	EG0003 affected147 at risk EG0010 affected147 at risk
Ureteric obstruction	Renal and urinary disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 affected147 at risk EG0011 affected147 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 affected147 at risk EG0011 affected147 at risk
Pneumonia aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 affected147 at risk EG0011 affected147 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 affected147 at risk EG0010 affected147 at risk
Bleeding varicose vein	Vascular disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 affected147 at risk EG0011 affected147 at risk
Deep vein thrombosis	Vascular disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 affected147 at risk EG0011 affected147 at risk
Peripheral embolism	Vascular disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 affected147 at risk EG0011 affected147 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA (18.0)	Non-systematic Assessment	EG00047 affected147 at risk EG00140 affected147 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA (18.0)	Non-systematic Assessment	EG00026 affected147 at risk EG00124 affected147 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA (18.0)	Non-systematic Assessment	EG00061 affected147 at risk EG00169 affected147 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA (18.0)	Non-systematic Assessment	EG00014 affected147 at risk EG00114 affected147 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0008 affected147 at risk EG0017 affected147 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG00012 affected147 at risk EG00111 affected147 at risk
Constipation	Gastrointestinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG00019 affected147 at risk EG00125 affected147 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG00024 affected147 at risk EG00130 affected147 at risk
Nausea	Gastrointestinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG00055 affected147 at risk EG00155 affected147 at risk
Vomiting	Gastrointestinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG00036 affected147 at risk EG00142 affected147 at risk
Asthenia	General disorders	MedDRA (18.0)	Non-systematic Assessment	EG00016 affected147 at risk EG00111 affected147 at risk
Fatigue	General disorders	MedDRA (18.0)	Non-systematic Assessment	EG00025 affected147 at risk EG00123 affected147 at risk
Oedema peripheral	General disorders	MedDRA (18.0)	Non-systematic Assessment	EG0009 affected147 at risk EG0016 affected147 at risk
Pyrexia	General disorders	MedDRA (18.0)	Non-systematic Assessment	EG00015 affected147 at risk EG00114 affected147 at risk
Weight decreased	Investigations	MedDRA (18.0)	Non-systematic Assessment	EG00010 affected147 at risk EG00117 affected147 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA (18.0)	Non-systematic Assessment	EG00032 affected147 at risk EG00127 affected147 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA (18.0)	Non-systematic Assessment	EG0005 affected147 at risk EG00110 affected147 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA (18.0)	Non-systematic Assessment	EG0009 affected147 at risk EG0019 affected147 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (18.0)	Non-systematic Assessment	EG0006 affected147 at risk EG00115 affected147 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA (18.0)	Non-systematic Assessment	EG0003 affected147 at risk EG0018 affected147 at risk
Dizziness	Nervous system disorders	MedDRA (18.0)	Non-systematic Assessment	EG0008 affected147 at risk EG0012 affected147 at risk
Chronic kidney disease	Renal and urinary disorders	MedDRA (18.0)	Non-systematic Assessment	EG0007 affected147 at risk EG00113 affected147 at risk
Renal failure	Renal and urinary disorders	MedDRA (18.0)	Non-systematic Assessment	EG0005 affected147 at risk EG0018 affected147 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0009 affected147 at risk EG0013 affected147 at risk
Palmar-plantar erythrodysaesthesia syndrome	Skin and subcutaneous tissue disorders	MedDRA (18.0)	Non-systematic Assessment	EG00014 affected147 at risk EG00120 affected147 at risk

Certain Agreements

Ancestor Terms

ID	Term
D003841	Deoxycytidine
D003562	Cytidine
D011741	Pyrimidine Nucleosides
D011743	Pyrimidines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D005472	Fluorouracil
D014498	Uracil
D011744	Pyrimidinones
D003853	Deoxyribonucleosides
D009705	Nucleosides
D009706	Nucleic Acids, Nucleotides, and Nucleosides
D017606	Chlorine Compounds
D007287	Inorganic Chemicals
D017672	Nitrogen Compounds
D017671	Platinum Compounds
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

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