A Study of Paclitaxel With or Without Ramucirumab (LY3009806) in Participants With Gastric or Gastroesophageal Cancer

• ClinicalTrials.gov Identifier: NCT02898077
• Recruitment Status: Completed
• First Posted: September 13, 2016
• Results First Posted: August 3, 2021
• Last Update Posted: June 14, 2022
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Conditions: Gastroesophageal Junction Adenocarcinoma; Gastric Adenocarcinoma
• Interventions: Drug: Ramucirumab; Drug: Paclitaxel; Drug: Placebo
• Enrollment: 440

Participant Flow

Recruitment Details
Pre-assignment Details	In the Participant Flow, participants who completed were those who died on treatment or during follow-up.

Arm/Group Title	8 Milligram/Kilogram (mg/kg) Ramucirumab + 80 mg/Square Meter (mg/m²) Paclitaxel	Placebo + 80 mg/m² Paclitaxel
Arm/Group Description	8 mg/kg ramucirumab was administered as an intravenous infusion (IV) on days 1 and 15, in combination with 80 mg/m² paclitaxel administered by IV on days 1, 8, and 15 of every 28-day cycle. Participants may continue on treatment until discontinuation criteria were met.	Placebo was administered at a volume equivalent to a dose of 8 mg/kg by IV on Days 1 and 15, in combination with 80 mg/m² paclitaxel administered by IV on Days 1, 8, and 15 of a 28-day cycle. Participants may continue on treatment until discontinuation criteria were met.
Period Title: Overall Study
Started	294	146
Received at Least 1 Dose of Study Drug	293	145
Completed	246	123
Not Completed	48	23
Reason Not Completed
Enrolled/randomized, but never treated	1	1
Lost to Follow-up	4	3
Physician Decision	0	2
Sponsor Decision	32	13
Withdrawal by Subject	6	3
Discontinued from treatment but refused follow-up	2	1
Ended extension period	3	0

Baseline Characteristics

Arm/Group Title		8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel	Placebo + 80 mg/m² Paclitaxel	Total
Arm/Group Description		8 mg/kg ramucirumab was administered as an IV on days 1 and 15, in combination with 80 mg/m² paclitaxel administered by IV on days 1, 8, and 15 of every 28-day cycle. Participants may continue on treatment until discontinuation criteria were met.	Placebo was administered at a volume equivalent to a dose of 8 mg/kg by IV on Days 1 and 15, in combination with 80 mg/m² paclitaxel administered by IV on Days 1, 8, and 15 of a 28-day cycle. Participants may continue on treatment until discontinuation criteria were met.	Total of all reporting groups
Overall Number of Baseline Participants		294	146	440
Baseline Analysis Population Description		All randomized participants.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	294 participants	146 participants	440 participants
		56.00 (11.49)	56.20 (11.12)	56.10 (11.35)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	294 participants	146 participants	440 participants
	Female	89	50	139
	Male	205	96	301
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	294 participants	146 participants	440 participants
	American Indian or Alaska Native	0	0	0
	Asian	290	145	435
	Native Hawaiian or Other Pacific Islander	0	0	0
	Black or African American	0	0	0
	White	1	0	1
	More than one race	3	1	4
	Unknown or Not Reported	0	0	0
Region of Enrollment; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	294 participants	146 participants	440 participants
China		257	135	392
Malaysia		18	7	25
Philippines		6	2	8
Thailand		13	2	15

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival (PFS)
Description	PFS defined as the time from the date of randomization to the first evidence of disease progression as defined by response evaluation criteria in solid tumors (RECIST) v1.1 or death from any cause. Progressive Disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. If a participant does not have a complete baseline disease assessment, then the PFS time was censored at the date of randomization, regardless of whether or not objectively determined disease progression or death has been observed for the participant. If a participant was not known to have died or have objective progression as of the data inclusion cutoff date for the analysis, the PFS time was censored at the last adequate tumor assessment date.
Time Frame	Randomization to the Date of the First Radiographically Documented Progressive Disease or Death from Any Cause (Up To 30 Months)

Outcome Measure Data

Analysis Population Description

All randomized participants. Censored participants: Ramucirumab +Paclitaxel = 67, Placebo + Paclitaxel = 16.

Arm/Group Title	8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel	Placebo + 80 mg/m² Paclitaxel
Arm/Group Description:	8 mg/kg ramucirumab was administered as an IV on days 1 and 15, in combination with 80 mg/m² paclitaxel administered by IV on days 1, 8, and 15 of every 28-day cycle. Participants may continue on treatment until discontinuation criteria were met.	Placebo was administered at a volume equivalent to a dose of 8 mg/kg by IV on Days 1 and 15, in combination with 80 mg/m² paclitaxel administered by IV on Days 1, 8, and 15 of a 28-day cycle. Participants may continue on treatment until discontinuation criteria were met.
Overall Number of Participants Analyzed	294	146
Median (95% Confidence Interval); Unit of Measure: Months
	4.14; (3.71 to 4.30)	3.15; (2.83 to 4.14)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel, Placebo + 80 mg/m² Paclitaxel
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0184
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.765
	Confidence Interval	(2-Sided) 95%; 0.613 to 0.955
	Estimation Comments	[Not Specified]

2. Primary Outcome

Title	Overall Survival (OS)
Description	OS defined as the time from randomization to the date of death due to any cause. For each participant who is not known to have died as of the data-inclusion cutoff date for overall survival analysis, OS time was censored on the last date the participant is known to be alive.
Time Frame	Randomization to Date of Death from Any Cause (Up To 37 Months)

Outcome Measure Data

Analysis Population Description

All randomized participants. Censored participants: Ramucirumab +Paclitaxel = 52, Placebo + Paclitaxel = 25.

Arm/Group Title	8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel	Placebo + 80 mg/m² Paclitaxel
Arm/Group Description:	8 mg/kg ramucirumab was administered as an IV on days 1 and 15, in combination with 80 mg/m² paclitaxel administered by IV on days 1, 8, and 15 of every 28-day cycle. Participants may continue on treatment until discontinuation criteria were met.	Placebo was administered at a volume equivalent to a dose of 8 mg/kg by IV on Days 1 and 15, in combination with 80 mg/m² paclitaxel administered by IV on Days 1, 8, and 15 of a 28-day cycle. Participants may continue on treatment until discontinuation criteria were met.
Overall Number of Participants Analyzed	294	146
Median (95% Confidence Interval); Unit of Measure: Months
	8.71; (7.98 to 9.49)	7.92; (6.31 to 9.10)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel, Placebo + 80 mg/m² Paclitaxel
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.963
	Confidence Interval	(2-Sided) 95%; 0.771 to 1.203
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	Time to Progression (TTP)
Description	TTP was time from the date of randomization to the date of radiographic progression (according to RECIST v.1.1). If a participant died due to any reason without radiographic progression, TTP is censored at the last adequate tumor assessment. Target lesions: Progressive Disease (PD): At least a 20% increase in the sum of diameters of lesions vs the smallest sum on study (the sum must also demonstrate an absolute increase of at least 5 mm); or the appearance of new lesion(s). Non target lesions: PD: Unequivocal progression of existing lesions or the appearance of new lesion(s).
Time Frame	Randomization to the Date of the First Radiographically Documented Progressive Disease (Up To 30 Months)

Outcome Measure Data

Analysis Population Description

All randomized participants. Censored participants: Ramucirumab +Paclitaxel = 98, Placebo + Paclitaxel = 36.

Arm/Group Title	8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel	Placebo + 80 mg/m² Paclitaxel
Arm/Group Description:	8 mg/kg ramucirumab was administered as an IV on days 1 and 15, in combination with 80 mg/m² paclitaxel administered by IV on days 1, 8, and 15 of every 28-day cycle. Participants may continue on treatment until discontinuation criteria were met.	Placebo was administered at a volume equivalent to a dose of 8 mg/kg by IV on Days 1 and 15, in combination with 80 mg/m² paclitaxel administered by IV on Days 1, 8, and 15 of a 28-day cycle. Participants may continue on treatment until discontinuation criteria were met.
Overall Number of Participants Analyzed	294	146
Median (95% Confidence Interval); Unit of Measure: Months
	4.27; (4.14 to 5.52)	4.07; (2.92 to 4.17)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel, Placebo + 80 mg/m² Paclitaxel
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.761
	Confidence Interval	(2-Sided) 95%; 0.598 to 0.968
	Estimation Comments	[Not Specified]

4. Secondary Outcome

Title	Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])
Description	ORR was the percentage of participants achieving a best overall response (BOR) of complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. PD was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.
Time Frame	Randomization to Objective Disease Progression (Up To 30 Months)

Outcome Measure Data

Analysis Population Description

All randomized participants.

Arm/Group Title	8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel	Placebo + 80 mg/m² Paclitaxel
Arm/Group Description:	8 mg/kg ramucirumab was administered as an IV on days 1 and 15, in combination with 80 mg/m² paclitaxel administered by IV on days 1, 8, and 15 of every 28-day cycle. Participants may continue on treatment until discontinuation criteria were met.	Placebo was administered at a volume equivalent to a dose of 8 mg/kg by IV on Days 1 and 15, in combination with 80 mg/m² paclitaxel administered by IV on Days 1, 8, and 15 of a 28-day cycle. Participants may continue on treatment until discontinuation criteria were met.
Overall Number of Participants Analyzed	294	146
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
	26.5; (21.6 to 32.0)	21.9; (15.5 to 29.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel, Placebo + 80 mg/m² Paclitaxel
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.8
	Confidence Interval	(2-Sided) 95%; 0.5 to 1.2
	Estimation Comments	[Not Specified]

5. Secondary Outcome

Title	Duration of Objective Response (DoR)
Description	DOR was the time from the date of first evidence of complete response or partial response to the date of objective progression or the date of death due to any cause, whichever is earlier. CR and PR were defined using the RECIST v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. If a responder was not known to have died or have objective progression as of the data inclusion cutoff date, duration of response was censored at the last adequate tumor assessment date. PD was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.
Time Frame	Date of Objective Response to the Date of the First Radiographically Documented Progressive Disease or Death Due to Any Cause (Up To 24 Months)

Outcome Measure Data

Analysis Population Description

All randomized participants with response. Censored participants: Ramucirumab +Paclitaxel = 1, Placebo + Paclitaxel = 4.

Arm/Group Title	8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel	Placebo + 80 mg/m² Paclitaxel
Arm/Group Description:	8 mg/kg ramucirumab was administered as an IV on days 1 and 15, in combination with 80 mg/m² paclitaxel administered by IV on days 1, 8, and 15 of every 28-day cycle. Participants may continue on treatment until discontinuation criteria were met.	Placebo was administered at a volume equivalent to a dose of 8 mg/kg by IV on Days 1 and 15, in combination with 80 mg/m² paclitaxel administered by IV on Days 1, 8, and 15 of a 28-day cycle. Participants may continue on treatment until discontinuation criteria were met.
Overall Number of Participants Analyzed	78	32
Median (95% Confidence Interval); Unit of Measure: Months
	4.34; (3.12 to 5.22)	2.83; (2.56 to 4.14)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel, Placebo + 80 mg/m² Paclitaxel
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.905
	Confidence Interval	(2-Sided) 95%; 0.577 to 1.421
	Estimation Comments	[Not Specified]

6. Secondary Outcome

Title	Best Change From Baseline on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)
Description	EORTC QLQ-C30 v3.0 was a self-administered questionnaire with multidimensional scales that measures global health status, 5 functional domains (physical, role, cognitive, emotional, and social) and symptom scales of fatigue, pain, nausea and vomiting, dyspnea, loss of appetite, insomnia, constipation, diarrhea, and financial difficulties. A linear transformation is applied to standardize the raw scores to range between 0 and 100 per developer guidelines. For functional domains and global health status, scores range from 0 to 100 with higher scores representing a better level of functioning. For symptoms scales, scores range from 0 to 100 with higher scores representing a greater degree of symptoms. Least square (LS) mean value of changing from baseline to short-term follow up was estimated from the mixed model that was controlled for Treatment, visit, Treatment*Visit and baseline.
Time Frame	Baseline, 30 Days After Treatment Discontinuation (Up To 20 Months)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug with baseline and post-baseline EORTC QLQ-C30 data at short term follow up for each EORTC QLQ-C30 items.

Arm/Group Title	8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel	Placebo + 80 mg/m² Paclitaxel
Arm/Group Description:	8 mg/kg ramucirumab was administered as an IV on days 1 and 15, in combination with 80 mg/m² paclitaxel administered by IV on days 1, 8, and 15 of every 28-day cycle. Participants may continue on treatment until discontinuation criteria were met.	Placebo was administered at a volume equivalent to a dose of 8 mg/kg by IV on Days 1 and 15, in combination with 80 mg/m² paclitaxel administered by IV on Days 1, 8, and 15 of a 28-day cycle. Participants may continue on treatment until discontinuation criteria were met.
Overall Number of Participants Analyzed	272	133
Least Squares Mean (Standard Error); Unit of Measure: Units on a scale
Global health status	5.30 (1.18)	8.43 (1.56)
Functional scale: Physical functioning	1.09 (0.82)	1.20 (1.10)
Functional scale: Role functioning	0.60 (1.13)	1.27 (1.49)
Functional scale: Emotional functioning	5.89 (0.90)	4.72 (1.19)
Functional scale: Cognitive functioning	2.87 (0.84)	2.12 (1.11)
Functional scale: Social functioning	2.71 (1.19)	2.98 (1.59)
Symptom scale: Fatigue	-4.20 (1.14)	-5.63 (1.51)
Symptom scale: Nausea and vomiting	-4.84 (0.77)	-3.80 (1.03)
Symptom scale: Pain	-6.89 (1.07)	-7.01 (1.43)
Symptom scale: Dyspnea	-2.18 (0.95)	-2.65 (1.27)
Symptom scale: Insomnia	-5.73 (1.18)	-7.06 (1.57)
Symptom scale: Appetite loss	-7.84 (1.30)	-10.26 (1.73)
Symptom scale: Constipation	-6.35 (1.11)	-5.41 (1.48)
Symptom scale: Diarrhea	-2.51 (0.86)	-3.03 (1.14)
Symptom scale: Financial difficulties	-8.49 (1.60)	-8.12 (2.13)

7. Secondary Outcome

Title	Worst Change From Baseline on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)
Description	EORTC QLQ-C30 v3.0 was a self-administered questionnaire with multidimensional scales that measures global health status, 5 functional domains (physical, role, cognitive, emotional, and social) and symptom scales of fatigue, pain, nausea and vomiting, dyspnea, loss of appetite, insomnia, constipation, diarrhea, and financial difficulties. A linear transformation is applied to standardize the raw scores to range between 0 and 100 per developer guidelines. For functional domains and global health status, scores range from 0 to 100 with higher scores representing a better level of functioning. For symptoms scales, scores range from 0 to 100 with higher scores representing a greater degree of symptoms. LS Mean value of changing from baseline to short-term follow up was estimated from the mixed model that was controlled for Treatment, visit, Treatment*Visit and baseline.
Time Frame	Baseline, 30 Days After Treatment Discontinuation (Up To 20 Months)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug with baseline and post-baseline EORTC QLQ-C30 data at short term follow up for each EORTC QLQ-C30 items.

Arm/Group Title	8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel	Placebo + 80 mg/m² Paclitaxel
Arm/Group Description:	8 mg/kg ramucirumab was administered as an IV on days 1 and 15, in combination with 80 mg/m² paclitaxel administered by IV on days 1, 8, and 15 of every 28-day cycle. Participants may continue on treatment until discontinuation criteria were met.	Placebo was administered at a volume equivalent to a dose of 8 mg/kg by IV on Days 1 and 15, in combination with 80 mg/m² paclitaxel administered by IV on Days 1, 8, and 15 of a 28-day cycle. Participants may continue on treatment until discontinuation criteria were met.
Overall Number of Participants Analyzed	272	133
Least Squares Mean (Standard Error); Unit of Measure: Units on a scale
Global health status	-14.42 (1.32)	-9.83 (1.75)
Functional scale: Physical functioning	-14.31 (1.30)	-11.71 (1.73)
Functional scale: Role functioning	-18.46 (1.72)	-14.39 (2.28)
Functional scale: Emotional functioning	-9.80 (1.30)	-6.77 (1.72)
Functional scale: Cognitive functioning	-13.66 (1.40)	-12.08 (1.85)
Functional scale: Social functioning	-17.05 (1.73)	-16.52 (2.30)
Symptom scale: Fatigue	15.28 (1.36)	10.17 (1.80)
Symptom scale: Nausea and vomiting	8.57 (1.46)	8.66 (1.95)
Symptom scale: Pain	14.01 (1.50)	10.11 (2.00)
Symptom scale: Dyspnea	16.58 (1.51)	8.34 (2.01)
Symptom scale: Insomnia	14.14 (1.74)	7.97 (2.32)
Symptom scale: Appetite loss	17.06 (1.85)	11.11 (2.46)
Symptom scale: Constipation	8.39 (1.57)	6.58 (2.08)
Symptom scale: Diarrhea	13.41 (1.39)	5.67 (1.85)
Symptom scale: Financial difficulties	10.11 (1.80)	9.32 (2.39)

8. Secondary Outcome

Title	Change From Baseline in Participant-Reported European-Quality of Life-5 Dimension Instrument-3 Levels (EQ-5D-3L) Index Score
Description	EQ-5D-3L is a descriptive system of health-related quality of life states consisting of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and each of which has 3 levels of severity (no problems/some or moderate problems/extreme problems) within a particular EQ-5D dimension. A regression equation defines a utility value for these health states to generate an index score. The possible values for index score range from -0.594 (severe problems in all 5 dimensions) to 1 (no problem in all dimensions) on a scale where 1 represents the best possible health state.
Time Frame	Baseline, 30 Days After Treatment Discontinuation (Up To 20 Months)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug with baseline and post-baseline EQ-5D 3L data.

Arm/Group Title	8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel	Placebo + 80 mg/m² Paclitaxel
Arm/Group Description:	8 mg/kg ramucirumab was administered as an IV on days 1 and 15, in combination with 80 mg/m² paclitaxel administered by IV on days 1, 8, and 15 of every 28-day cycle. Participants may continue on treatment until discontinuation criteria were met.	Placebo was administered at a volume equivalent to a dose of 8 mg/kg by IV on Days 1 and 15, in combination with 80 mg/m² paclitaxel administered by IV on Days 1, 8, and 15 of a 28-day cycle. Participants may continue on treatment until discontinuation criteria were met.
Overall Number of Participants Analyzed	123	56
Mean (Standard Deviation); Unit of Measure: Units on a scale
	-0.1351 (0.2472)	-0.1303 (0.1765)

9. Secondary Outcome

Title	Change From Baseline in Participant-Reported EQ-5D-3L Visual Analog Scale (VAS) Score
Description	EQ-5D-3L is a descriptive system of health-related quality of life states consisting of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and each of which has 3 levels of severity (no problems/some or moderate problems/extreme problems) within a particular EQ-5D dimension. The EQ-5D VAS is used to record a participant's rating for his/her current health-related quality of life state on the day of questionnaire administration and is captured on a scale of 0 (worst imaginable health state) to 100 (best imaginable health state).
Time Frame	Baseline, 30 Days After Treatment Discontinuation (Up To 20 Months)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug with baseline and post-baseline EQ-5D 3L data.

Arm/Group Title	8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel	Placebo + 80 mg/m² Paclitaxel
Arm/Group Description:	8 mg/kg ramucirumab was administered as an IV on days 1 and 15, in combination with 80 mg/m² paclitaxel administered by IV on days 1, 8, and 15 of every 28-day cycle. Participants may continue on treatment until discontinuation criteria were met.	Placebo was administered at a volume equivalent to a dose of 8 mg/kg by IV on Days 1 and 15, in combination with 80 mg/m² paclitaxel administered by IV on Days 1, 8, and 15 of a 28-day cycle. Participants may continue on treatment until discontinuation criteria were met.
Overall Number of Participants Analyzed	123	56
Mean (Standard Deviation); Unit of Measure: millimeter (mm)
	-9.6 (20.11)	-8.6 (15.88)

Adverse Events

Time Frame	Adverse Events: Randomization Up To 26 Months; All-Cause Mortality: Randomization to Date of Death from Any Cause (Up To 37 Months)
Adverse Event Reporting Description	Adverse events: All randomized participants who received at least 1 dose of study drug. Mortality: All randomized participants.
Arm/Group Title	8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel		Placebo + 80 mg/m² Paclitaxel
Arm/Group Description	8 mg/kg ramucirumab was administered as an IV on days 1 and 15, in combination with 80 mg/m² paclitaxel administered by IV on days 1, 8, and 15 of every 28-day cycle. Participants may continue on treatment until discontinuation criteria were met.		Placebo was administered at a volume equivalent to a dose of 8 mg/kg by IV on Days 1 and 15, in combination with 80 mg/m² paclitaxel administered by IV on Days 1, 8, and 15 of a 28-day cycle. Participants may continue on treatment until discontinuation criteria were met.
All-Cause Mortality
	8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel		Placebo + 80 mg/m² Paclitaxel
	Affected / at Risk (%)		Affected / at Risk (%)
Total	246/294 (83.67%)		123/146 (84.25%)
Serious Adverse Events
	8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel		Placebo + 80 mg/m² Paclitaxel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	100/293 (34.13%)		37/145 (25.52%)
Blood and lymphatic system disorders
Anaemia † 1	6/293 (2.05%)	6	4/145 (2.76%)	4
Blood loss anaemia † 1	1/293 (0.34%)	1	0/145 (0.00%)	0
Bone marrow toxicity † 1	5/293 (1.71%)	5	0/145 (0.00%)	0
Febrile neutropenia † 1	13/293 (4.44%)	14	0/145 (0.00%)	0
Haemolytic anaemia † 1	0/293 (0.00%)	0	1/145 (0.69%)	1
Neutropenia † 1	1/293 (0.34%)	1	1/145 (0.69%)	1
Cardiac disorders
Left ventricular dysfunction † 1	1/293 (0.34%)	1	0/145 (0.00%)	0
Myocardial infarction † 1	0/293 (0.00%)	0	1/145 (0.69%)	1
Eye disorders
Blindness † 1	0/293 (0.00%)	0	1/145 (0.69%)	1
Gastrointestinal disorders
Abdominal distension † 1	2/293 (0.68%)	2	0/145 (0.00%)	0
Abdominal pain † 1	3/293 (1.02%)	3	1/145 (0.69%)	1
Abdominal pain upper † 1	2/293 (0.68%)	2	0/145 (0.00%)	0
Ascites † 1	2/293 (0.68%)	2	0/145 (0.00%)	0
Diarrhoea † 1	1/293 (0.34%)	1	0/145 (0.00%)	0
Dysphagia † 1	1/293 (0.34%)	1	0/145 (0.00%)	0
Gastric haemorrhage † 1	1/293 (0.34%)	1	0/145 (0.00%)	0
Gastrointestinal haemorrhage † 1	0/293 (0.00%)	0	3/145 (2.07%)	4
Gastrointestinal obstruction † 1	1/293 (0.34%)	1	0/145 (0.00%)	0
Haematemesis † 1	1/293 (0.34%)	1	0/145 (0.00%)	0
Ileus † 1	4/293 (1.37%)	5	2/145 (1.38%)	2
Intestinal obstruction † 1	3/293 (1.02%)	3	2/145 (1.38%)	3
Intestinal prolapse † 1	1/293 (0.34%)	1	0/145 (0.00%)	0
Mesenteric panniculitis † 1	0/293 (0.00%)	0	1/145 (0.69%)	1
Obstruction gastric † 1	2/293 (0.68%)	2	0/145 (0.00%)	0
Upper gastrointestinal haemorrhage † 1	9/293 (3.07%)	10	1/145 (0.69%)	1
Vomiting † 1	4/293 (1.37%)	4	4/145 (2.76%)	4
General disorders
Asthenia † 1	1/293 (0.34%)	1	0/145 (0.00%)	0
Fatigue † 1	0/293 (0.00%)	0	2/145 (1.38%)	2
Influenza like illness † 1	1/293 (0.34%)	1	0/145 (0.00%)	0
Malaise † 1	3/293 (1.02%)	3	0/145 (0.00%)	0
Mass † 1	1/293 (0.34%)	1	0/145 (0.00%)	0
Multiple organ dysfunction syndrome † 1	2/293 (0.68%)	2	0/145 (0.00%)	0
Oedema peripheral † 1	1/293 (0.34%)	1	0/145 (0.00%)	0
Pyrexia † 1	7/293 (2.39%)	7	2/145 (1.38%)	2
Sudden cardiac death † 1	1/293 (0.34%)	1	1/145 (0.69%)	1
Sudden death † 1	0/293 (0.00%)	0	1/145 (0.69%)	1
Hepatobiliary disorders
Cholecystitis acute † 1	1/293 (0.34%)	1	0/145 (0.00%)	0
Cholelithiasis † 1	1/293 (0.34%)	1	0/145 (0.00%)	0
Drug-induced liver injury † 1	1/293 (0.34%)	1	0/145 (0.00%)	0
Hepatic function abnormal † 1	3/293 (1.02%)	3	2/145 (1.38%)	2
Liver injury † 1	1/293 (0.34%)	1	0/145 (0.00%)	0
Infections and infestations
Anal abscess † 1	1/293 (0.34%)	1	0/145 (0.00%)	0
Anal infection † 1	1/293 (0.34%)	1	0/145 (0.00%)	0
Bacteraemia † 1	1/293 (0.34%)	1	0/145 (0.00%)	0
Biliary sepsis † 1	0/293 (0.00%)	0	1/145 (0.69%)	2
Device related infection † 1	0/293 (0.00%)	0	1/145 (0.69%)	1
Escherichia sepsis † 1	1/293 (0.34%)	1	0/145 (0.00%)	0
Gingivitis † 1	1/293 (0.34%)	1	0/145 (0.00%)	0
Herpes zoster † 1	0/293 (0.00%)	0	1/145 (0.69%)	1
Neutropenic sepsis † 1	1/293 (0.34%)	1	0/145 (0.00%)	0
Pneumonia † 1	10/293 (3.41%)	10	5/145 (3.45%)	5
Post procedural infection † 1	1/293 (0.34%)	1	0/145 (0.00%)	0
Pulmonary tuberculosis † 1	1/293 (0.34%)	1	0/145 (0.00%)	0
Sepsis † 1	3/293 (1.02%)	3	1/145 (0.69%)	1
Streptococcal sepsis † 1	1/293 (0.34%)	1	0/145 (0.00%)	0
Urinary tract infection † 1	1/293 (0.34%)	2	1/145 (0.69%)	1
Injury, poisoning and procedural complications
Anastomotic fistula † 1	1/293 (0.34%)	1	0/145 (0.00%)	0
Craniocerebral injury † 1	0/293 (0.00%)	0	1/145 (0.69%)	1
Fracture † 1	1/293 (0.34%)	1	0/145 (0.00%)	0
Investigations
Blood bilirubin increased † 1	0/293 (0.00%)	0	1/145 (0.69%)	1
Neutrophil count decreased † 1	15/293 (5.12%)	26	3/145 (2.07%)	3
Platelet count decreased † 1	9/293 (3.07%)	10	0/145 (0.00%)	0
White blood cell count decreased † 1	12/293 (4.10%)	21	2/145 (1.38%)	2
Metabolism and nutrition disorders
Decreased appetite † 1	0/293 (0.00%)	0	1/145 (0.69%)	1
Electrolyte imbalance † 1	0/293 (0.00%)	0	1/145 (0.69%)	1
Hyperkalaemia † 1	1/293 (0.34%)	1	0/145 (0.00%)	0
Hypokalaemia † 1	0/293 (0.00%)	0	2/145 (1.38%)	3
Hyponatraemia † 1	1/293 (0.34%)	1	0/145 (0.00%)	0
Hypoproteinaemia † 1	1/293 (0.34%)	1	0/145 (0.00%)	0
Malnutrition † 1	0/293 (0.00%)	0	1/145 (0.69%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Sebaceous adenoma † 1	1/293 (0.34%)	1	0/145 (0.00%)	0
Nervous system disorders
Cerebral infarction † 1	2/293 (0.68%)	2	0/145 (0.00%)	0
Ischaemic cerebral infarction † 1	0/293 (0.00%)	0	1/145 (0.69%)	1
Neuropathy peripheral † 1	1/293 (0.34%)	1	0/145 (0.00%)	0
Psychiatric disorders
Completed suicide † 1	1/293 (0.34%)	1	0/145 (0.00%)	0
Delirium † 1	0/293 (0.00%)	0	1/145 (0.69%)	1
Renal and urinary disorders
Acute kidney injury † 1	1/293 (0.34%)	2	0/145 (0.00%)	0
Haematuria † 1	1/293 (0.34%)	1	0/145 (0.00%)	0
Proteinuria † 1	2/293 (0.68%)	2	0/145 (0.00%)	0
Renal impairment † 1	1/293 (0.34%)	1	1/145 (0.69%)	1
Respiratory, thoracic and mediastinal disorders
Acquired tracheo-oesophageal fistula † 1	1/293 (0.34%)	1	0/145 (0.00%)	0
Dyspnoea † 1	1/293 (0.34%)	2	0/145 (0.00%)	0
Interstitial lung disease † 1	0/293 (0.00%)	0	1/145 (0.69%)	1
Pleural effusion † 1	2/293 (0.68%)	2	1/145 (0.69%)	1
Pneumothorax † 1	1/293 (0.34%)	1	0/145 (0.00%)	0
Productive cough † 1	1/293 (0.34%)	1	0/145 (0.00%)	0
Pulmonary embolism † 1	0/293 (0.00%)	0	1/145 (0.69%)	1
Respiratory failure † 1	1/293 (0.34%)	1	1/145 (0.69%)	1
Skin and subcutaneous tissue disorders
Decubitus ulcer † 1	1/293 (0.34%)	1	0/145 (0.00%)	0
Vascular disorders
Embolism venous † 1	1/293 (0.34%)	1	0/145 (0.00%)	0
1 Term from vocabulary, MedDRA 23.0; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel		Placebo + 80 mg/m² Paclitaxel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	287/293 (97.95%)		143/145 (98.62%)
Blood and lymphatic system disorders
Anaemia † 1	195/293 (66.55%)	338	94/145 (64.83%)	161
Leukopenia † 1	17/293 (5.80%)	64	3/145 (2.07%)	6
Neutropenia † 1	16/293 (5.46%)	59	2/145 (1.38%)	3
Gastrointestinal disorders
Abdominal distension † 1	47/293 (16.04%)	54	15/145 (10.34%)	17
Abdominal pain † 1	38/293 (12.97%)	45	26/145 (17.93%)	32
Abdominal pain upper † 1	27/293 (9.22%)	38	4/145 (2.76%)	4
Ascites † 1	16/293 (5.46%)	17	7/145 (4.83%)	7
Constipation † 1	50/293 (17.06%)	64	26/145 (17.93%)	30
Diarrhoea † 1	71/293 (24.23%)	111	21/145 (14.48%)	40
Gingival bleeding † 1	16/293 (5.46%)	24	1/145 (0.69%)	1
Nausea † 1	54/293 (18.43%)	67	22/145 (15.17%)	29
Vomiting † 1	51/293 (17.41%)	79	22/145 (15.17%)	27
General disorders
Fatigue † 1	28/293 (9.56%)	31	8/145 (5.52%)	9
Influenza like illness † 1	9/293 (3.07%)	9	11/145 (7.59%)	14
Malaise † 1	74/293 (25.26%)	94	37/145 (25.52%)	47
Oedema peripheral † 1	35/293 (11.95%)	40	10/145 (6.90%)	10
Pain † 1	20/293 (6.83%)	22	12/145 (8.28%)	18
Pyrexia † 1	53/293 (18.09%)	72	24/145 (16.55%)	32
Infections and infestations
Pneumonia † 1	12/293 (4.10%)	14	9/145 (6.21%)	10
Upper respiratory tract infection † 1	25/293 (8.53%)	29	7/145 (4.83%)	7
Urinary tract infection † 1	9/293 (3.07%)	13	11/145 (7.59%)	14
Investigations
Alanine aminotransferase increased † 1	88/293 (30.03%)	160	31/145 (21.38%)	43
Aspartate aminotransferase increased † 1	100/293 (34.13%)	216	35/145 (24.14%)	55
Bilirubin conjugated increased † 1	7/293 (2.39%)	9	9/145 (6.21%)	12
Blood alkaline phosphatase increased † 1	34/293 (11.60%)	53	17/145 (11.72%)	23
Blood bilirubin increased † 1	65/293 (22.18%)	135	35/145 (24.14%)	57
Blood creatinine increased † 1	13/293 (4.44%)	14	8/145 (5.52%)	10
Blood lactate dehydrogenase increased † 1	9/293 (3.07%)	13	9/145 (6.21%)	14
Gamma-glutamyltransferase increased † 1	36/293 (12.29%)	45	14/145 (9.66%)	21
Lymphocyte count decreased † 1	27/293 (9.22%)	59	8/145 (5.52%)	13
Neutrophil count decreased † 1	223/293 (76.11%)	892	102/145 (70.34%)	286
Platelet count decreased † 1	88/293 (30.03%)	232	17/145 (11.72%)	29
Weight decreased † 1	59/293 (20.14%)	75	22/145 (15.17%)	27
White blood cell count decreased † 1	227/293 (77.47%)	926	107/145 (73.79%)	351
White blood cell count increased † 1	6/293 (2.05%)	6	9/145 (6.21%)	12
Metabolism and nutrition disorders
Decreased appetite † 1	81/293 (27.65%)	99	32/145 (22.07%)	37
Hyperglycaemia † 1	27/293 (9.22%)	41	21/145 (14.48%)	38
Hyperuricaemia † 1	10/293 (3.41%)	21	8/145 (5.52%)	10
Hypoalbuminaemia † 1	90/293 (30.72%)	125	31/145 (21.38%)	53
Hypocalcaemia † 1	46/293 (15.70%)	64	14/145 (9.66%)	20
Hypochloraemia † 1	5/293 (1.71%)	5	8/145 (5.52%)	8
Hypokalaemia † 1	32/293 (10.92%)	44	15/145 (10.34%)	23
Hyponatraemia † 1	31/293 (10.58%)	41	23/145 (15.86%)	28
Hypophosphataemia † 1	20/293 (6.83%)	46	4/145 (2.76%)	6
Musculoskeletal and connective tissue disorders
Back pain † 1	32/293 (10.92%)	41	14/145 (9.66%)	21
Pain in extremity † 1	9/293 (3.07%)	9	8/145 (5.52%)	8
Nervous system disorders
Dizziness † 1	13/293 (4.44%)	16	8/145 (5.52%)	12
Headache † 1	18/293 (6.14%)	25	3/145 (2.07%)	3
Hypoaesthesia † 1	36/293 (12.29%)	42	22/145 (15.17%)	25
Paraesthesia † 1	26/293 (8.87%)	27	10/145 (6.90%)	11
Psychiatric disorders
Insomnia † 1	37/293 (12.63%)	47	11/145 (7.59%)	12
Renal and urinary disorders
Proteinuria † 1	99/293 (33.79%)	164	31/145 (21.38%)	57
Respiratory, thoracic and mediastinal disorders
Cough † 1	30/293 (10.24%)	32	9/145 (6.21%)	13
Epistaxis † 1	53/293 (18.09%)	71	9/145 (6.21%)	11
Productive cough † 1	16/293 (5.46%)	17	6/145 (4.14%)	6
Skin and subcutaneous tissue disorders
Alopecia † 1	83/293 (28.33%)	88	55/145 (37.93%)	57
Rash † 1	17/293 (5.80%)	21	3/145 (2.07%)	3
Vascular disorders
Hypertension † 1	66/293 (22.53%)	137	25/145 (17.24%)	43
1 Term from vocabulary, MedDRA 23.0; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Chief Medical Officer
• Organization: Eli Lilly and Company
• Phone: 800-545-5979
• EMail: ClinicalTrials.gov@lilly.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Xu RH, Zhang Y, Pan H, Feng J, Zhang T, Liu T, Qin Y, Qin S, Yin X, Liu B, Ba Y, Yang N, Voon PJ, Tanasanvimon S, Zhou C, Zhang WL, Shen L. Efficacy and safety of weekly paclitaxel with or without ramucirumab as second-line therapy for the treatment of advanced gastric or gastroesophageal junction adenocarcinoma (RAINBOW-Asia): a randomised, multicentre, double-blind, phase 3 trial. Lancet Gastroenterol Hepatol. 2021 Dec;6(12):1015-1024. doi: 10.1016/S2468-1253(21)00313-7. Epub 2021 Oct 7.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT02898077
• Other Study ID Numbers: 15244; I4T-CR-JVCR ( Other Identifier: Eli Lilly and Company )
• First Submitted: September 8, 2016
• First Posted: September 13, 2016
• Results First Submitted: June 10, 2021
• Results First Posted: August 3, 2021
• Last Update Posted: June 14, 2022