Diffuse Gastric and Esophagogastric Junction Cancer S-1 T... | NCT01285557

NCT01285557

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
S-1+Cisplatin	Experimental	Participants received S-1 25 milligrams per meter square (mg/m^2) orally twice daily (BID) every 12 hours from Day 1 through Day 21, 1 hour before or after meal with a glass of water; followed by a 7-day rest period from Day 22 to Day 28 in a 28-day cycle. Participants received a single dose of cisplatin 75 mg/m^2 as a 1- to 3-hour intravenous (IV) infusion on Day 1 following the morning dose of S-1 for a maximum of 8 cycles (each cycle of 28 days). Participants received study medication until progression of disease (PD), adverse event (AE), withdrawal of consent, or other reason for discontinuation, whichever happened earlier.	Drug: S-1 (Tegafur+Gimeracil+Oteracil) /cisplatin (investigational arm)
5FU+Cisplatin	Active Comparator	Participants received 5-Fluorouracil (5-FU) 800 mg/m^2 per 24 hours as continuous IV infusion over 120 hours from Day 1 through Day 5 followed by a 16-day rest period on Days 6 through 21 in a 21-day cycle. Participants received a single dose of cisplatin 80 mg/m^2 as a 1- to 3-hour IV infusion on Day 1 prior to the start of the 5-FU infusion on Day 1 for a maximum of 8 cycles (each cycle of 21 days). Participants received study medication until PD, AE, withdrawal of consent, or other reason for discontinuation, whichever happened earlier.	Drug: Fluorouracil/cisplatin (control arm)

Interventions

Name	Type	Description	Arm Group Labels	Other Names
S-1 (Tegafur+Gimeracil+Oteracil) /cisplatin (investigational arm)	Drug	25 mg/m² body surface area (BSA) orally 2 times daily from Days 1 through 21 followed by a 7 day rest period, plus cisplatin 75 mg/m2 BSA on Day 1 each 28 day cycle Number of Cycles: until progression or unacceptable toxicity develops. Treatment with cisplatin is limited to a maximum of 8 cycles.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Overall Survival (OS)	OS was defined as the time from randomization to the date of death for the ITT population. Participants who did not die were censored at the date last known to be alive. Analysis was performed by using Kaplan-Meier method.	From the date of randomization until disease progression or death, cut-off date: 15 August 2014 (approximately 40 months)

Secondary Outcomes

Measure	Description	Time Frame
Progression-free Survival (PFS)	PFS was defined as the time from date of randomization until date of radiological disease progression or death due to any cause. Disease Progression was defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, where any of the 3 criteria have been met: 1) at least 20% increase in the sum of diameters of the target lesions, taking as reference the smallest sum on study, including the baseline sum, 2) Progression in no-target lesion(s), 3) appearance of new lesion(s) Participants who were alive with no PD were censored at the date of the last tumor assessment. Participants who received new anticancer therapy before disease progression were censored at the date of the last evaluable tumor assessment before new anticancer therapy was initiated. Analysis was performed by using Kaplan-Meier method.

Eligibility Module

Contacts/Locations Module

Name	Affiliation	Role
Taiho Central	Taiho Oncology, Inc. USA	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
		Alexandria	Louisiana	71301	United States

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
28911091	Derived	Ajani JA, Abramov M, Bondarenko I, Shparyk Y, Gorbunova V, Hontsa A, Otchenash N, Alsina M, Lazarev S, Feliu J, Elme A, Esko V, Abdalla K, Verma U, Benedetti F, Aoyama T, Mizuguchi H, Makris L, Rosati G; DIGEST Study Group. A phase III trial comparing oral S-1/cisplatin and intravenous 5-fluorouracil/cisplatin in patients with untreated diffuse gastric cancer. Ann Oncol. 2017 Sep 1;28(9):2142-2148. doi: 10.1093/annonc/mdx275.

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	S-1+Cisplatin	Participants received S-1 25 milligrams per meter square (mg/m^2) orally twice daily (BID) every 12 hours from Day 1 through Day 21, 1 hour before or after meal with a glass of water; followed by a 7-day rest period from Day 22 to Day 28 in a 28-day cycle. Participants received a single dose of cisplatin 75 mg/m^2 as a 1- to 3-hour intravenous (IV) infusion on Day 1 following the morning dose of S-1 for a maximum of 8 cycles (each cycle of 28 days). Participants received study medication until progression of disease (PD), adverse event (AE), withdrawal of consent, or other reason for discontinuation, whichever happened earlier.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

The Intent-to-Treat (ITT) population included all randomized participants including those not dosed according to their randomization.

Arm/Group Information

ID	Title	Description
BG000	S-1+Cisplatin	Participants received S-1 25 mg/m^2 orally BID every 12 hours from Day 1 through Day 21, 1 hour before or after meal with a glass of water; followed by a 7-day rest period from Day 22 to Day 28 in a 28-day cycle. Participants received a single dose of cisplatin 75 mg/m^2 as a 1- to 3-hour IV infusion on Day 1 following the morning dose of S-1 for a maximum of 8 cycles (each cycle of 28 days). Participants received study medication until PD, AE, withdrawal of consent, or other reason for discontinuation, whichever happened earlier.
BG001	5FU+Cisplatin	Participants received 5-FU 800 mg/m^2 per 24 hours as continuous IV infusion over 120 hours from Day 1 through Day 5 followed by a 16-day rest period on Days 6 through 21 in a 21-day cycle. Participants received a single dose of cisplatin 80 mg/m^2 as a 1- to 3-hour IV infusion on Day 1 prior to the start of the 5-FU infusion on Day 1 for a maximum of 8 cycles (each cycle of 21 days). Participants received study medication until PD, AE, withdrawal of consent, or other reason for discontinuation, whichever happened earlier.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00055.1± 11.01 BG00155.8± 11.80 BG00255.4± 11.27

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000115 BG00162 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

Caucasian/White

Title	Measurements
	BG000226 BG001117 BG002

Eastern Cooperative Oncology Group (ECOG) Performance Status

The ECOG performance status was used to evaluate participant's disease progression and the effect of the disease on the participant's activities of daily living. It ranged on the scale from 0-5 (0 equal to [=] normal activity; 1= symptoms but ambulatory; 2= in bed for less than (<) 50 percent (%) of the time; 3= in bed for greater than (>) 50% of the time; 4= 100% bedridden; 5= dead).

Count of Participants

Participants

Title

Denominators

Categories

ECOG Grade 0

Title	Measurements
	BG00075 BG001

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Overall Survival (OS)

OS was defined as the time from randomization to the date of death for the ITT population. Participants who did not die were censored at the date last known to be alive. Analysis was performed by using Kaplan-Meier method.

Analysis was performed on the ITT population that included all randomized participants.

Posted

Median

95% Confidence Interval

months

From the date of randomization until disease progression or death, cut-off date: 15 August 2014 (approximately 40 months)

ID	Title	Description
OG000	S-1+Cisplatin	Participants received S-1 25 mg/m^2 orally BID every 12 hours from Day 1 through Day 21, 1 hour before or after meal with a glass of water; followed by a 7-day rest period from Day 22 to Day 28 in a 28-day cycle. Participants received a single dose of cisplatin 75 mg/m^2 as a 1- to 3-hour IV infusion on Day 1 following the morning dose of S-1 for a maximum of 8 cycles (each cycle of 28 days). Participants received study medication until PD, AE, withdrawal of consent, or other reason for discontinuation, whichever happened earlier.
OG001	5FU+Cisplatin	Participants received 5-FU 800 mg/m^2 per 24 hours as continuous IV infusion over 120 hours from Day 1 through Day 5 followed by a 16-day rest period on Days 6 through 21 in a 21-day cycle. Participants received a single dose of cisplatin 80 mg/m^2 as a 1- to 3-hour IV infusion on Day 1 prior to the start of the 5-FU infusion on Day 1 for a maximum of 8 cycles (each cycle of 21 days). Participants received study medication until PD, AE, withdrawal of consent, or other reason for discontinuation, whichever happened earlier.

Units	Counts
Participants	OG000239 OG001122

Title

Denominators

Categories

Title	Measurements
	OG0007.5(6.7 to 9.3) OG0016.6(5.7 to 8.1)

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	S-1+Cisplatin and 5FU+Cisplatin were compared using the unstratified log-rank test. The hazard ratio was estimated using a Cox's regression approach and survival was summarized using Kaplan Meier estimates along with 2-sided 95% confidence intervals (CI) for the estimates.	Unstratified Log-rank		0.9312		Hazard Ratio (HR)	0.99			2-Sided	95	0.76	1.28					Superiority

Secondary

Progression-free Survival (PFS)

PFS was defined as the time from date of randomization until date of radiological disease progression or death due to any cause. Disease Progression was defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, where any of the 3 criteria have been met: 1) at least 20% increase in the sum of diameters of the target lesions, taking as reference the smallest sum on study, including the baseline sum, 2) Progression in no-target lesion(s), 3) appearance of new lesion(s) Participants who were alive with no PD were censored at the date of the last tumor assessment. Participants who received new anticancer therapy before disease progression were censored at the date of the last evaluable tumor assessment before new anticancer therapy was initiated. Analysis was performed by using Kaplan-Meier method.

Analysis was performed on the ITT population.

Posted

Median

95% Confidence Interval

months

From date of randomization until disease progression or death, cut-off date: 07 March 2014 (approximately 34.7 months)

ID	Title	Description
OG000	S-1+Cisplatin	Participants received S-1 25 mg/m^2 orally BID every 12 hours from Day 1 through Day 21, 1 hour before or after meal with a glass of water; followed by a 7-day rest period from Day 22 to Day 28 in a 28-day cycle. Participants received a single dose of cisplatin 75 mg/m^2 as a 1- to 3-hour IV infusion on Day 1 following the morning dose of S-1 for a maximum of 8 cycles (each cycle of 28 days). Participants received study medication until PD, AE, withdrawal of consent, or other reason for discontinuation, whichever happened earlier.

Secondary

Time to Treatment Failure (TTF)

TTF was defined as the time from date of randomization until date of PD (clinical or radiologic), or permanent discontinuation of study treatment (S-1 or 5-FU), or death due to any cause. Participates who were still on study treatment at the time of the analysis were censored at the last date the participants was known to be on treatment.

Analysis was performed on the ITT population.

Posted

Median

95% Confidence Interval

months

From date of randomization until disease progression, cut-off date: 07 March 2014 (approximately 34.7 months)

ID	Title	Description
OG000	S-1+Cisplatin	Participants received S-1 25 mg/m^2 orally BID every 12 hours from Day 1 through Day 21, 1 hour before or after meal with a glass of water; followed by a 7-day rest period from Day 22 to Day 28 in a 28-day cycle. Participants received a single dose of cisplatin 75 mg/m^2 as a 1- to 3-hour IV infusion on Day 1 following the morning dose of S-1 for a maximum of 8 cycles (each cycle of 28 days). Participants received study medication until PD, AE, withdrawal of consent, or other reason for discontinuation, whichever happened earlier.
OG001	5FU+Cisplatin	Participants received 5-FU 800 mg/m^2 per 24 hours as continuous IV infusion over 120 hours from Day 1 through Day 5 followed by a 16-day rest period on Days 6 through 21 in a 21-day cycle. Participants received a single dose of cisplatin 80 mg/m^2 as a 1- to 3-hour IV infusion on Day 1 prior to the start of the 5-FU infusion on Day 1 for a maximum of 8 cycles (each cycle of 21 days). Participants received study medication until PD, AE, withdrawal of consent, or other reason for discontinuation, whichever happened earlier.

Secondary

Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAE)

AE was defined as any untoward medical condition that occurs in a participants while participating in a clinical study and does not necessarily had to have a causal relationship with the use of the study medication. A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. TEAEs were defined as AEs that developed or worsened or became serious during on-treatment period (from first dose of study medication up to 30 days of last study medication [maximum duration: 35.7 months]).

Analysis was performed on the as treated (AT) population that included all participants who initiated treatment with either of the 2 regimens with treatment assignment designated according to actual treatment received.

Posted

Count of Participants

Participants

From first dose of study medication up to 30 days of last study medication (maximum duration: 35.7 months)

ID	Title	Description
OG000	S-1+Cisplatin	Participants received S-1 25 mg/m^2 orally BID every 12 hours from Day 1 through Day 21, 1 hour before or after meal with a glass of water; followed by a 7-day rest period from Day 22 to Day 28 in a 28-day cycle. Participants received a single dose of cisplatin 75 mg/m^2 as a 1- to 3-hour IV infusion on Day 1 following the morning dose of S-1 for a maximum of 8 cycles (each cycle of 28 days). Participants received study medication until PD, AE, withdrawal of consent, or other reason for discontinuation, whichever happened earlier.

Secondary

Number of Participants With TEAEs With Severity Greater Than or Equal to (>=) Grade 3

An AE was any untoward medical condition that occurred in a participants while participating in a clinical study and does not necessarily had to have a causal relationship with the use of the study medication. TEAEs were defined as AEs that developed or worsened or became serious during on-treatment period (from first dose of study medication up to 30 days of last study medication [maximum duration: 35.7 months]).

Analysis was performed on the as treated (AT) population.

Posted

Count of Participants

Participants

From first dose of study medication up to 30 days of last study medication (maximum duration: 35.7 months)

ID	Title	Description
OG000	S-1+Cisplatin	Participants received S-1 25 mg/m^2 orally BID every 12 hours from Day 1 through Day 21, 1 hour before or after meal with a glass of water; followed by a 7-day rest period from Day 22 to Day 28 in a 28-day cycle. Participants received a single dose of cisplatin 75 mg/m^2 as a 1- to 3-hour IV infusion on Day 1 following the morning dose of S-1 for a maximum of 8 cycles (each cycle of 28 days). Participants received study medication until PD, AE, withdrawal of consent, or other reason for discontinuation, whichever happened earlier.
OG001	5FU+Cisplatin	Participants received 5-FU 800 mg/m^2 per 24 hours as continuous IV infusion over 120 hours from Day 1 through Day 5 followed by a 16-day rest period on Days 6 through 21 in a 21-day cycle. Participants received a single dose of cisplatin 80 mg/m^2 as a 1- to 3-hour IV infusion on Day 1 prior to the start of the 5-FU infusion on Day 1 for a maximum of 8 cycles (each cycle of 21 days). Participants received study medication until PD, AE, withdrawal of consent, or other reason for discontinuation, whichever happened earlier.

Secondary

Overall Response Rate (ORR): Percentage of Participants With Overall Response

ORR was defined as the percentage of participants with objective evidence of complete response (CR) or partial response (PR) based on the Investigator review of the images and application of Response Evaluation Criteria in Solid Tumors (RECIST) criteria. CR was defined as the disappearance of all target or non-target lesions. Any pathological lymph nodes for target lesions or all lymph nodes for non-target lesions were non-pathological morphologically that was reduced in size in short axis to less than (<) 10 millimeter (mm). PR was defined as target lesions with at least 30% decrease in the sum of diameters, taking baseline sum diameters as reference.

Analysis was performed on the ITT population. Here, 'overall number of participants analyzed' signifies participants with available data for the outcome measure.

Posted

Number

95% Confidence Interval

percentage of participants

From date of first study medication until cut-off date: 07 March 2014 (approximately 34.7 months)

ID	Title	Description
OG000	S-1+Cisplatin	Participants received S-1 25 mg/m^2 orally BID every 12 hours from Day 1 through Day 21, 1 hour before or after meal with a glass of water; followed by a 7-day rest period from Day 22 to Day 28 in a 28-day cycle. Participants received a single dose of cisplatin 75 mg/m^2 as a 1- to 3-hour IV infusion on Day 1 following the morning dose of S-1 for a maximum of 8 cycles (each cycle of 28 days). Participants received study medication until PD, AE, withdrawal of consent, or other reason for discontinuation, whichever happened earlier.

Secondary

Duration of Response (DR)

Duration of response was defined as the time (in months) from date of first confirmed response (CR or PR) to date of first progressive disease (PD) or death. Per the RECIST criteria, definitions were as follows: CR was defined as the disappearance of all target or non-target lesions. Any pathological lymph nodes for target lesions or all lymph nodes for non-target lesions were non-pathological morphologically that was reduced in size in short axis to <10 mm. Analysis was performed by using Kaplan-Meier method.

Analysis was performed on the ITT population. Here, 'overall number of participants analyzed' signifies participants with available data for the outcome measure.

Posted

Median

95% Confidence Interval

months

From date of first study medication until cut-off date: 07 March 2014 (approximately 34.7 months)

ID	Title	Description
OG000	S-1+Cisplatin	Participants received S-1 25 mg/m^2 orally BID every 12 hours from Day 1 through Day 21, 1 hour before or after meal with a glass of water; followed by a 7-day rest period from Day 22 to Day 28 in a 28-day cycle. Participants received a single dose of cisplatin 75 mg/m^2 as a 1- to 3-hour IV infusion on Day 1 following the morning dose of S-1 for a maximum of 8 cycles (each cycle of 28 days). Participants received study medication until PD, AE, withdrawal of consent, or other reason for discontinuation, whichever happened earlier.
OG001	5FU+Cisplatin

Secondary

Time to Tumor Response (TTR)

TTR was defined as the time (in months) from the date of randomization to the date of first observation of response (PR or CR) (whichever status was recorded first). TTR was assessed based on investigator assessment utilizing RECIST 1.1. CR was defined as the disappearance of all target or non-target lesions. Any pathological lymph nodes for target lesions or all lymph nodes for non-target lesions were non-pathological morphologically that was reduced in size in short axis to <10 mm. PR was defined as target lesions with at least 30% decrease in the sum of diameters, taking baseline sum diameters as reference. Analysis was performed by using Kaplan-Meier method.

Analysis was performed on the ITT population. Here, 'overall number of participants analyzed' signifies participants with available data for the outcome measure.

Posted

Median

95% Confidence Interval

months

From date of first study medication until cut-off date: 07 March 2014 (approximately 34.7 months)

ID	Title	Description
OG000	S-1+Cisplatin	Participants received S-1 25 mg/m^2 orally BID every 12 hours from Day 1 through Day 21, 1 hour before or after meal with a glass of water; followed by a 7-day rest period from Day 22 to Day 28 in a 28-day cycle. Participants received a single dose of cisplatin 75 mg/m^2 as a 1- to 3-hour IV infusion on Day 1 following the morning dose of S-1 for a maximum of 8 cycles (each cycle of 28 days). Participants received study medication until PD, AE, withdrawal of consent, or other reason for discontinuation, whichever happened earlier.
OG001

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	S-1+Cisplatin	Participants received S-1 25 mg/m^2 orally BID every 12 hours from Day 1 through Day 21, 1 hour before or after meal with a glass of water; followed by a 7-day rest period from Day 22 to Day 28 in a 28-day cycle. Participants received a single dose of cisplatin 75 mg/m^2 as a 1- to 3-hour IV infusion on Day 1 following the morning dose of S-1 for a maximum of 8 cycles (each cycle of 28 days). Participants received study medication until PD, AE, withdrawal of consent, or other reason for discontinuation, whichever happened earlier.	173	239	63	230	210	230
EG001	5FU+Cisplatin	Participants received 5-FU 800 mg/m^2 per 24 hours as continuous IV infusion over 120 hours from Day 1 through Day 5 followed by a 16-day rest period on Days 6 through 21 in a 21-day cycle. Participants received a single dose of cisplatin 80 mg/m^2 as a 1- to 3-hour IV infusion on Day 1 prior to the start of the 5-FU infusion on Day 1 for a maximum of 8 cycles (each cycle of 21 days). Participants received study medication until PD, AE, withdrawal of consent, or other reason for discontinuation, whichever happened earlier.	90	122	31	118	110	118

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 14.0	Systematic Assessment	EG00012 events11 affected230 at risk EG0015 events5 affected118 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 14.0	Systematic Assessment	EG0000 events0 affected230 at risk EG0013 events2 affected118 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 14.0	Systematic Assessment	EG0002 events2 affected230 at risk EG0011 events1 affected118 at risk
Pancytopenia	Blood and lymphatic system disorders	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected230 at risk EG0011 events1 affected118 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected230 at risk EG0011 events1 affected118 at risk
Acute coronary syndrome	Cardiac disorders	MedDRA 14.0	Systematic Assessment	EG0000 events0 affected230 at risk EG0011 events1 affected118 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected118 at risk
Cytotoxic cardiomyopathy	Cardiac disorders	MedDRA 14.0	Systematic Assessment	EG0000 events0 affected230 at risk EG0011 events1 affected118 at risk
Vertigo positional	Ear and labyrinth disorders	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected118 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected118 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0003 events3 affected230 at risk EG0010 events0 affected118 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0002 events2 affected230 at risk EG0011 events1 affected118 at risk
Ascites	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0002 events1 affected230 at risk EG0011 events1 affected118 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0002 events2 affected230 at risk EG0011 events1 affected118 at risk
Dysphagia	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0004 events4 affected230 at risk EG0011 events1 affected118 at risk
Gastric haemorrhage	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0003 events3 affected230 at risk EG0014 events4 affected118 at risk
Gastric perforation	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0002 events2 affected230 at risk EG0011 events1 affected118 at risk
Gastric stenosis	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected118 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0002 events2 affected230 at risk EG0010 events0 affected118 at risk
Gastrointestinal obstruction	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected118 at risk
Haematemesis	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected230 at risk EG0012 events2 affected118 at risk
Haemorrhoids	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected118 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0005 events3 affected230 at risk EG0013 events2 affected118 at risk
Large intestinal obstruction	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected118 at risk
Melaena	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected118 at risk
Nausea	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0004 events4 affected230 at risk EG0011 events1 affected118 at risk
Obstruction gastric	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected118 at risk
Pancreatitis acute	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0002 events2 affected230 at risk EG0010 events0 affected118 at risk
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected118 at risk
Vomiting	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0005 events5 affected230 at risk EG0014 events4 affected118 at risk
Asthenia	General disorders	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected118 at risk
Death	General disorders	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected118 at risk
Device dislocation	General disorders	MedDRA 14.0	Systematic Assessment	EG0000 events0 affected230 at risk EG0011 events1 affected118 at risk
Device occlusion	General disorders	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected118 at risk
General physical health deterioration	General disorders	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected118 at risk
Infusion site extravasation	General disorders	MedDRA 14.0	Systematic Assessment	EG0000 events0 affected230 at risk EG0011 events1 affected118 at risk
Mucosal inflammation	General disorders	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected230 at risk EG0011 events1 affected118 at risk
Pyrexia	General disorders	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected230 at risk EG0011 events1 affected118 at risk
Systemic inflammatory response syndrome	General disorders	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected118 at risk
Cholecystitis acute	Hepatobiliary disorders	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected230 at risk EG0011 events1 affected118 at risk
Jaundice cholestatic	Hepatobiliary disorders	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected118 at risk
Abdominal infection	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected118 at risk
Biliary tract infection	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected118 at risk
Bronchopneumonia	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0000 events0 affected230 at risk EG0011 events1 affected118 at risk
Enterocolitis infectious	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected118 at risk
Infection	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected118 at risk
Lung infection	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected118 at risk
Neutropenic sepsis	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected118 at risk
Pneumonia	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0003 events3 affected230 at risk EG0010 events0 affected118 at risk
Pyelonephritis acute	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected118 at risk
Sepsis	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0002 events2 affected230 at risk EG0011 events1 affected118 at risk
Septic shock	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected118 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected118 at risk
Overdose	Injury, poisoning and procedural complications	MedDRA 14.0	Systematic Assessment	EG0000 events0 affected230 at risk EG0011 events1 affected118 at risk
Spinal fracture	Injury, poisoning and procedural complications	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected118 at risk
Toxicity to various agents	Injury, poisoning and procedural complications	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected118 at risk
Blood creatinine increased	Investigations	MedDRA 14.0	Systematic Assessment	EG0003 events3 affected230 at risk EG0011 events1 affected118 at risk
Neutrophil count decreased	Investigations	MedDRA 14.0	Systematic Assessment	EG0000 events0 affected230 at risk EG0011 events1 affected118 at risk
Platelet count decreased	Investigations	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected230 at risk EG0011 events1 affected118 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 14.0	Systematic Assessment	EG0003 events2 affected230 at risk EG0012 events2 affected118 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 14.0	Systematic Assessment	EG0006 events6 affected230 at risk EG0014 events4 affected118 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA 14.0	Systematic Assessment	EG0000 events0 affected230 at risk EG0011 events1 affected118 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 14.0	Systematic Assessment	EG0000 events0 affected230 at risk EG0016 events4 affected118 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected118 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 14.0	Systematic Assessment	EG0000 events0 affected230 at risk EG0011 events1 affected118 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 14.0	Systematic Assessment	EG0002 events2 affected230 at risk EG0010 events0 affected118 at risk
Paraneoplastic syndrome	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected118 at risk
Aphasia	Nervous system disorders	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected118 at risk
Cerebral haemorrhage	Nervous system disorders	MedDRA 14.0	Systematic Assessment	EG0002 events2 affected230 at risk EG0010 events0 affected118 at risk
Convulsion	Nervous system disorders	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected230 at risk EG0011 events1 affected118 at risk
Dizziness	Nervous system disorders	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected118 at risk
Extrapyramidal disorder	Nervous system disorders	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected118 at risk
Ischaemic stroke	Nervous system disorders	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected230 at risk EG0011 events1 affected118 at risk
Parkinson's disease	Nervous system disorders	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected118 at risk
Syncope	Nervous system disorders	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected118 at risk
Confusional state	Psychiatric disorders	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected230 at risk EG0011 events1 affected118 at risk
Renal failure acute	Renal and urinary disorders	MedDRA 14.0	Systematic Assessment	EG0005 events5 affected230 at risk EG0011 events1 affected118 at risk
Ureteric obstruction	Renal and urinary disorders	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected118 at risk
Urinary tract obstruction	Renal and urinary disorders	MedDRA 14.0	Systematic Assessment	EG0000 events0 affected230 at risk EG0011 events1 affected118 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected230 at risk EG0011 events1 affected118 at risk
Pulmonary artery thrombosis	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected118 at risk
Deep vein thrombosis	Vascular disorders	MedDRA 14.0	Systematic Assessment	EG0003 events3 affected230 at risk EG0011 events1 affected118 at risk
Hypovolaemic shock	Vascular disorders	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected230 at risk EG0010 events0 affected118 at risk
Pulmonary embolism	Vascular disorders	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected230 at risk EG0012 events2 affected118 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 14.0	Systematic Assessment	EG000160 events97 affected230 at risk EG00186 events49 affected118 at risk
Granulocytopenia	Blood and lymphatic system disorders	MedDRA 14.0	Systematic Assessment	EG00059 events13 affected230 at risk EG0018 events5 affected118 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA 14.0	Systematic Assessment	EG00080 events31 affected230 at risk EG00123 events12 affected118 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 14.0	Systematic Assessment	EG000161 events68 affected230 at risk EG00192 events43 affected118 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 14.0	Systematic Assessment	EG00074 events37 affected230 at risk EG00112 events10 affected118 at risk
Tinnitus	Ear and labyrinth disorders	MedDRA 14.0	Systematic Assessment	EG00027 events19 affected230 at risk EG00122 events11 affected118 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG00033 events18 affected230 at risk EG00111 events5 affected118 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG00062 events42 affected230 at risk EG00114 events12 affected118 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG00020 events16 affected230 at risk EG00110 events10 affected118 at risk
Ascites	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG00015 events13 affected230 at risk EG0018 events8 affected118 at risk
Constipation	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG00052 events39 affected230 at risk EG00132 events17 affected118 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG00074 events41 affected230 at risk EG00146 events22 affected118 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0008 events8 affected230 at risk EG0017 events6 affected118 at risk
Dysphagia	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0008 events6 affected230 at risk EG00113 events8 affected118 at risk
Nausea	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG000272 events122 affected230 at risk EG001131 events62 affected118 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0004 events4 affected230 at risk EG00136 events18 affected118 at risk
Vomiting	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG000142 events82 affected230 at risk EG00159 events34 affected118 at risk
Asthenia	General disorders	MedDRA 14.0	Systematic Assessment	EG00080 events55 affected230 at risk EG00161 events36 affected118 at risk
Fatigue	General disorders	MedDRA 14.0	Systematic Assessment	EG000104 events59 affected230 at risk EG00151 events28 affected118 at risk
Mucosal inflammation	General disorders	MedDRA 14.0	Systematic Assessment	EG00023 events20 affected230 at risk EG00136 events19 affected118 at risk
Oedema peripheral	General disorders	MedDRA 14.0	Systematic Assessment	EG00020 events17 affected230 at risk EG0019 events7 affected118 at risk
Pyrexia	General disorders	MedDRA 14.0	Systematic Assessment	EG00027 events19 affected230 at risk EG0018 events7 affected118 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 14.0	Systematic Assessment	EG00013 events12 affected230 at risk EG0014 events4 affected118 at risk
Blood bilirubin increased	Investigations	MedDRA 14.0	Systematic Assessment	EG00017 events13 affected230 at risk EG0011 events1 affected118 at risk
Blood creatinine increased	Investigations	MedDRA 14.0	Systematic Assessment	EG00026 events20 affected230 at risk EG00111 events8 affected118 at risk
Creatinine renal clearance decreased	Investigations	MedDRA 14.0	Systematic Assessment	EG0009 events9 affected230 at risk EG00110 events8 affected118 at risk
Weight decreased	Investigations	MedDRA 14.0	Systematic Assessment	EG00042 events40 affected230 at risk EG00118 events18 affected118 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 14.0	Systematic Assessment	EG000184 events95 affected230 at risk EG00168 events40 affected118 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 14.0	Systematic Assessment	EG0006 events6 affected230 at risk EG00113 events7 affected118 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 14.0	Systematic Assessment	EG00030 events24 affected230 at risk EG00111 events9 affected118 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 14.0	Systematic Assessment	EG0007 events5 affected230 at risk EG00111 events6 affected118 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 14.0	Systematic Assessment	EG00016 events16 affected230 at risk EG0017 events5 affected118 at risk
Headache	Nervous system disorders	MedDRA 14.0	Systematic Assessment	EG00032 events18 affected230 at risk EG0017 events7 affected118 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA 14.0	Systematic Assessment	EG00028 events23 affected230 at risk EG00117 events14 affected118 at risk
Insomnia	Psychiatric disorders	MedDRA 14.0	Systematic Assessment	EG00014 events13 affected230 at risk EG0015 events5 affected118 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG00019 events15 affected230 at risk EG0015 events5 affected118 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG00026 events19 affected230 at risk EG00113 events8 affected118 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 14.0	Systematic Assessment	EG0007 events7 affected230 at risk EG00110 events10 affected118 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 14.0	Systematic Assessment	EG00016 events13 affected230 at risk EG0018 events6 affected118 at risk
Dizziness	Vascular disorders	MedDRA 14.0	Systematic Assessment	EG00032 events15 affected230 at risk EG0011 events1 affected118 at risk

Enrollment closure and study termination was due to significant changes in investigational and clinical practice landscape of frontline advanced gastric cancer, which challenged viability of trial and increased use of modified chemotherapeutic triplets led to slow participant accrual in the study. The decision to halt further accrual was not based on any safety or study quality concerns.

Certain Agreements

ID	Term
D013274	Stomach Neoplasms

Ancestor Terms

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

ID	Term
C079198	S 1 (combination)
C586502	tegafur-gimeracil-oteracil
D002945	Cisplatin
C103828	titanium silicide
D005472	Fluorouracil

Ancestor Terms

ID	Term
D017606	Chlorine Compounds
D007287	Inorganic Chemicals
D017672	Nitrogen Compounds
D017671	Platinum Compounds
D014498	Uracil
D011744	Pyrimidinones
D011743	Pyrimidines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds

Participants received 5-FU 800 mg/m^2 per 24 hours as continuous IV infusion over 120 hours from Day 1 through Day 5 followed by a 16-day rest period on Days 6 through 21 in a 21-day cycle. Participants received a single dose of cisplatin 80 mg/m^2 as a 1- to 3-hour IV infusion on Day 1 prior to the start of the 5-FU infusion on Day 1 for a maximum of 8 cycles (each cycle of 21 days). Participants received study medication until PD, AE, withdrawal of consent, or other reason for discontinuation, whichever happened earlier.