A Study of Paclitaxel With or Without Ramucirumab (IMC-1211B) in Metastatic Gastric Adenocarcinoma (RAINBOW)

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ClinicalTrials.gov Identifier: NCT01170663

Recruitment Status : Completed

First Posted : July 27, 2010

Results First Posted : July 31, 2014

Last Update Posted : September 18, 2019

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Sponsor:

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
Condition	Gastric Cancer
Interventions	Biological: Ramucirumab (IMC-1211B) DP Drug: Placebo Drug: Paclitaxel
Enrollment	665

Participant Flow

Recruitment Details
Pre-assignment Details	Completers include participants that discontinued study drugs either due to progressive disease (PD), due to an adverse event or died due to any cause, but not necessarily had any survival-FU assessment done.


Arm/Group Title	Ramucirumab (IMC-1211B) Plus Paclitaxel	Placebo Plus Paclitaxel
Arm/Group Description	8 milligrams/kilogram (mg/kg) of ra...	Placebo was administered by IV infu...
Arm/Group Description	8 milligrams/kilogram (mg/kg) of ramucirumab (IMC-1121B) was administered by intravenous (IV) infusion on Days 1 and 15 in combination with 80 milligrams/square meter (mg/m²) paclitaxel administered by IV infusion on Days 1, 8, and 15 of a 28-day cycle.	Placebo was administered by IV infusion on Days 1 and 15, in combination with 80 mg/m² paclitaxel administered on Days 1, 8, and 15 of a 28-day cycle.
Period Title: Overall Study
Started ^[1]	330 ^[2]	335 ^[3]
Received Any Treatment (Safety Pop)	327	329
Completed	316	315
Not Completed	14	20
Reason Not Completed
Lost to Follow-up	3	9
Withdrawal of consent without follow-up	11	11
[1] One participant randomized to placebo/paclitaxel arm but received ramucirumab (IMC-1121B) in error. [2] Participant was included in ramucirumab (IMC-1121B)/paclitaxel treatment arm (safety population). [3] Participant was included in the placebo/paclitaxel treatment arm (intent-to-treat (ITT) population).

Baseline Characteristics

Arm/Group Title		Ramucirumab (IMC-1211B) Plus Paclitaxel	Placebo Plus Paclitaxel	Total
Arm/Group Description		8 mg/kg of ramucirumab (IMC-1121B) ...	Placebo was administered by IV infu...	Total of all reporting groups
Arm/Group Description		8 mg/kg of ramucirumab (IMC-1121B) was administered by IV infusion on Days 1 and 15 in combination with 80 mg/m² paclitaxel administered by IV infusion on Days 1, 8, and 15 of a 28-day cycle.	Placebo was administered by IV infusion on Days 1 and 15, in combination with 80 mg/m² paclitaxel administered on Days 1, 8, and 15 of a 28-day cycle.	Total of all reporting groups
Overall Number of Baseline Participants		330	335	665
Baseline Analysis Population Description		...
Baseline Analysis Population Description		All randomized participants.
Age, Categorical Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	330 participants	335 participants	665 participants
	<=18 years	0	0	0
	Between 18 and 65 years	205	213	418
	>=65 years	125	122	247
Age, Continuous Median (Full Range) Unit of measure: Years
	Number Analyzed	330 participants	335 participants	665 participants
		61 (25 to 83)	61 (24 to 84)	61 (24 to 84)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	330 participants	335 participants	665 participants
	Female	101	92	193
	Male	229	243	472
Ethnicity (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	330 participants	335 participants	665 participants
	Hispanic or Latino	31	26	57
	Not Hispanic or Latino	299	309	608
	Unknown or Not Reported	0	0	0
Race/Ethnicity, Customized Measure Type: Count of Participants Unit of measure: Participants	Number Analyzed	330 participants	335 participants	665 participants
American Indian or Alaska Native		0	1	1
Asian		110	121	231
Black or African American		6	6	12
White		208	199	407
More than one race		0	1	1
Other		6	7	13
Region of Enrollment Measure Type: Count of Participants Unit of measure: Participants	Number Analyzed	330 participants	335 participants	665 participants
Portugal		2	0	2
United States		12	12	24
Estonia		5	5	10
Taiwan		14	16	30
Spain		8	13	21
Russia		8	13	21
Chile		1	3	4
Italy		13	15	28
France		20	14	34
Australia		18	23	41
South Korea		23	22	45
Lithuania		6	6	12
Austria		4	2	6
United Kingdom		6	9	15
Hungary		20	9	29
Mexico		2	2	4
Argentina		1	0	1
Poland		15	18	33
Brazil		19	16	35
Belgium		12	14	26
Singapore		2	3	5
Romania		7	7	14
Bulgaria		7	5	12
Germany		20	20	40
Japan		68	72	140
Hong Kong		2	1	3
Israel		15	15	30

Outcome Measures

1.Primary Outcome


Title	Overall Survival Time (OS)
Description	OS time was measured from date of randomization to date of death from ...
Description	OS time was measured from date of randomization to date of death from any cause. Participants who were not known to have died on or before the date of data cut-off, OS data was censored on the last date (on or before the cut-off date) the participant was known to be alive.
Time Frame	Randomization up to 27.5 months

Outcome Measure Data

Analysis Population Description

All participants according to the treatment group to which they were randomized. Participants censored: Ramucirumab (IMC-1211B) plus Paclitaxel =74, Placebo plus Paclitaxel =75.


Arm/Group Title	Ramucirumab (IMC-1211B) Plus Paclitaxel	Placebo Plus Paclitaxel
Arm/Group Description:	8 mg/kg of ramucirumab (IMC-1121B) ...	Placebo was administered by IV infu...
Arm/Group Description:	8 mg/kg of ramucirumab (IMC-1121B) was administered by IV infusion on Days 1 and 15 in combination with 80 mg/m² paclitaxel administered by IV infusion on Days 1, 8, and 15 of a 28-day cycle.	Placebo was administered by IV infusion on Days 1 and 15, in combination with 80 mg/m² paclitaxel administered on Days 1, 8, and 15 of a 28-day cycle.
Overall Number of Participants Analyzed	330	335
Median (95% Confidence Interval) Unit of Measure: months
	9.6 (8.5 to 10.8)	7.4 (6.3 to 8.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramucirumab (IMC-1211B) Plus Paclitaxel, Placebo Plus Paclitaxel
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.0169
	Comments	[Not Specified]
	Method	Stratified Log Rank Test
	Comments	Adjusted for stratification factors: geographic region, time-to-progression from start of first-line therapy and disease measurability.

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.807
	Confidence Interval	(2-Sided) 95% 0.678 to 0.962
	Estimation Comments	[Not Specified]

2.Secondary Outcome


Title	Progression-Free Survival (PFS)
Description	PFS was measured from date of randomization to first radiographically ...
Description	PFS was measured from date of randomization to first radiographically documented progressive disease (PD) or death due to any cause. PD defined using Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1) as ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this included the baseline sum if that is the smallest on study). The sum must also demonstrate an absolute increase of at least 5 mm. Participants who had no baseline or post baseline radiological tumor assessment were censored at date of randomization. Participants who had no tumor progression or death within 2 scan intervals following the last assessment were censored at the date of last radiographic tumor assessment. Participants who began new anticancer treatment and had no tumor progression were censored at date of assessment prior to initiation of new therapy. Participants lost to follow-up or withdrew consent were censored at the date of their last assessment.
Time Frame	Randomization up to 22.2 months

Outcome Measure Data

Analysis Population Description

All participants according to the treatment group to which they were randomized. Participants censored: Ramucirumab (IMC-1211B) plus Paclitaxel =51, Placebo plus Paclitaxel =39.


Arm/Group Title	Ramucirumab (IMC-1211B) Plus Paclitaxel	Placebo Plus Paclitaxel
Arm/Group Description:	8 mg/kg of ramucirumab (IMC-1121B) ...	Placebo was administered by IV infu...
Arm/Group Description:	8 mg/kg of ramucirumab (IMC-1121B) was administered by IV infusion on Days 1 and 15 in combination with 80 mg/m² paclitaxel administered by IV infusion on Days 1, 8, and 15 of a 28-day cycle.	Placebo was administered by IV infusion on Days 1 and 15, in combination with 80 mg/m² paclitaxel administered on Days 1, 8, and 15 of a 28-day cycle.
Overall Number of Participants Analyzed	330	335
Median (95% Confidence Interval) Unit of Measure: months
	4.4 (4.2 to 5.3)	2.9 (2.8 to 3.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramucirumab (IMC-1211B) Plus Paclitaxel, Placebo Plus Paclitaxel
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Stratified Log Rank Test
	Comments	Adjusted for stratification factors: geographic region, time-to-progression from start of first-line therapy and disease measurability.

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.635
	Confidence Interval	(2-Sided) 95% 0.536 to 0.752
	Estimation Comments	[Not Specified]

3.Secondary Outcome


Title	Time to Progressive Disease (TTP)
Description	TTP was defined as the time from randomization until date of radiograp...
Description	TTP was defined as the time from randomization until date of radiographic progression using RECIST v1.1 criteria. PD was defined as having a ≥20% increase in sum of longest diameter (LD) of target lesions and at minimum 5 millimeters (mm) increase above nadir. Participants who did not progress or were lost to follow-up were censored at the date of last tumor assessment. Participants who had no baseline tumor assessment or no post baseline assessment and no death reported with 2 scan intervals post randomization were censored at date of randomization. Participants with no progression and not died within 2 scan intervals after last assessment were censored at date of last tumor assessment. Participants with no post baseline assessment or tumor progression but death reported within 2 scan intervals after randomization were censored at date of death.
Time Frame	Baseline up to 22.2 months

Outcome Measure Data

Analysis Population Description

All participants according to the treatment group to which they were randomized. Participants censored: Ramucirumab (IMC-1211B) plus Paclitaxel =107, Placebo plus Paclitaxel =94.


Arm/Group Title	Ramucirumab (IMC-1211B) Plus Paclitaxel	Placebo Plus Paclitaxel
Arm/Group Description:	8 mg/kg of ramucirumab (IMC-1121B) ...	Placebo was administered by IV infu...
Arm/Group Description:	8 mg/kg of ramucirumab (IMC-1121B) was administered by IV infusion on Days 1 and 15 in combination with 80 mg/m² paclitaxel administered by IV infusion on Days 1, 8, and 15 of a 28-day cycle.	Placebo was administered by IV infusion on Days 1 and 15, in combination with 80 mg/m² paclitaxel administered on Days 1, 8, and 15 of a 28-day cycle.
Overall Number of Participants Analyzed	330	335
Median (95% Confidence Interval) Unit of Measure: months
	5.52 (4.50 to 5.68)	3.02 (2.86 to 4.14)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramucirumab (IMC-1211B) Plus Paclitaxel, Placebo Plus Paclitaxel
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Stratified Log Rank Test
	Comments	Adjusted for stratification factors: geographic region, time-to-progression from start of first-line therapy and disease measurability.

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.596
	Confidence Interval	(2-Sided) 95% 0.494 to 0.720
	Estimation Comments	[Not Specified]

4.Secondary Outcome


Title	Best Overall Response (BOR) of Complete Response (CR), Partial Response (PR), Stable Disease (SD) or PD
Description	BOR was defined as the best response across all time points from rando...
Description	BOR was defined as the best response across all time points from randomization until radiologically confirmed PD using RECIST, v1.1 criteria. CR was defined as the disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm and normalization of tumor marker level of non-target lesions. PR was defined as having a ≥30% decrease in sum of LD of target lesions. PD was defined as having a ≥20% increase in sum of LD of target lesions and ≥5 mm increase above nadir. SD was defined as small changes that did not meet above criteria.
Time Frame	Randomization up to 22.2 months

Outcome Measure Data

Analysis Population Description

All participants according to the treatment group to which they were randomized.


Arm/Group Title	Ramucirumab (IMC-1211B) Plus Paclitaxel	Placebo Plus Paclitaxel
Arm/Group Description:	8 mg/kg of ramucirumab (IMC-1121B) ...	Placebo was administered by IV infu...
Arm/Group Description:	8 mg/kg of ramucirumab (IMC-1121B) was administered by IV infusion on Days 1 and 15 in combination with 80 mg/m² paclitaxel administered by IV infusion on Days 1, 8, and 15 of a 28-day cycle.	Placebo was administered by IV infusion on Days 1 and 15, in combination with 80 mg/m² paclitaxel administered on Days 1, 8, and 15 of a 28-day cycle.
Overall Number of Participants Analyzed	330	335
Measure Type: Number Unit of Measure: percentage of participants
CR	0.6	0.3
PR	27.3	15.8
SD	52.1	47.5
PD	13.0	24.8
Not Evaluable	0.3	0.9
No Tumor Response Evaluation	6.7	10.7

5.Secondary Outcome


Title	Percentage of Participants With CR or PR (Objective Response Rate [ORR])
Description	ORR was the percentage of participants who had CR or PR defined using ...
Description	ORR was the percentage of participants who had CR or PR defined using RECIST v1.1 criteria. CR was defined as the disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm and normalization of tumor marker level of non-target lesions. PR was defined as having a ≥30% decrease in sum of LD of target lesions. Percentage of participants calculated as: (number of participants with CR + PR)/(total number of participants)*100.
Time Frame	Randomization up to 22.2 months

Outcome Measure Data

Analysis Population Description

All participants according to the treatment group to which they were randomized.


Arm/Group Title	Ramucirumab (IMC-1211B) Plus Paclitaxel	Placebo Plus Paclitaxel
Arm/Group Description:	8 mg/kg of ramucirumab (IMC-1121B) ...	Placebo was administered by IV infu...
Arm/Group Description:	8 mg/kg of ramucirumab (IMC-1121B) was administered by IV infusion on Days 1 and 15 in combination with 80 mg/m² paclitaxel administered by IV infusion on Days 1, 8, and 15 of a 28-day cycle.	Placebo was administered by IV infusion on Days 1 and 15, in combination with 80 mg/m² paclitaxel administered on Days 1, 8, and 15 of a 28-day cycle.
Overall Number of Participants Analyzed	330	335
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: percentage of participants
	27.9 (23.3 to 33.0)	16.1 (12.6 to 20.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramucirumab (IMC-1211B) Plus Paclitaxel, Placebo Plus Paclitaxel
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.0001
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	Adjusted for stratification factors: geographic region, time-to-progression from the start of first-line therapy and disease measurability.

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.14
	Confidence Interval	(2-Sided) 95% 1.45 to 3.16
	Estimation Comments	[Not Specified]

6.Secondary Outcome


Title	Percentage of Participants With Anti-Ramucirumab Antibodies (Serum Anti-Ramucirumab Antibody Assessment )(Immunogenicity)
Description	Participants who developed treatment-emergent antibody responses to Ra...
Description	Participants who developed treatment-emergent antibody responses to Ramucirumab (IMC-1121B) after baseline.
Time Frame	Prior to and after ramucirumab (IMC-1121B) infusion: Day 1 Cycles 1, 2 and 3 (28-day cycles) Doses 1, 4, 7 and 30-37 days after last dose of study therapy up to 103 weeks

Outcome Measure Data

Analysis Population Description

All participants according to the treatment group to which they were randomized and received at least 1 dose of study drug with anti-ramucirumab antibodies.


Arm/Group Title	Ramucirumab (IMC-1211B) Plus Paclitaxel	Placebo Plus Paclitaxel
Arm/Group Description:	8 mg/kg of ramucirumab (IMC-1121B) ...	Placebo was administered by IV infu...
Arm/Group Description:	8 mg/kg of ramucirumab (IMC-1121B) was administered by IV infusion on Days 1 and 15 in combination with 80 mg/m² paclitaxel administered by IV infusion on Days 1, 8, and 15 of a 28-day cycle.	Placebo was administered by IV infusion on Days 1 and 15, in combination with 80 mg/m² paclitaxel administered on Days 1, 8, and 15 of a 28-day cycle.
Overall Number of Participants Analyzed	320	323
Measure Type: Number Unit of Measure: percentage of participants
	1.6	0.3

7.Secondary Outcome


Title	Maximum Concentration (Cmax) After First Ramucirumab (IMC-1211B) Infusion
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Cycle 1, Day 1, 1 hour post end of infusion (28-day cycles)

Outcome Measure Data

Analysis Population Description

All participants who received Ramucirumab (IMC-1121B) plus Paclitaxel and had Cmax observations at specific timepoint.


Arm/Group Title	Ramucirumab (IMC-1211B) Plus Paclitaxel
Arm/Group Description:	8 mg/kg of ramucirumab (IMC-1121B) ...
Arm/Group Description:	8 mg/kg of ramucirumab (IMC-1121B) was administered by IV infusion on Days 1 and 15 in combination with 80 mg/m² paclitaxel administered by IV infusion on Days 1, 8, and 15 of a 28-day cycle.
Overall Number of Participants Analyzed	259
Geometric Mean (Geometric Coefficient of Variation) Unit of Measure: micrograms/milliliter (µg/mL)
	146 (28%)

8.Secondary Outcome


Title	Cmax After 4th Ramucirumab (IMC-1211B) Infusion
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Cycle 2, Day 15 1 hour post end of infusion (28-day cycles)

Outcome Measure Data

Analysis Population Description

All participants who received Ramucirumab (IMC-1121B) plus Paclitaxel and had Cmax observations at specific timepoint.


Arm/Group Title	Ramucirumab (IMC-1211B) Plus Paclitaxel
Arm/Group Description:	8 mg/kg of ramucirumab (IMC-1121B) ...
Arm/Group Description:	8 mg/kg of ramucirumab (IMC-1121B) was administered by IV infusion on Days 1 and 15 in combination with 80 mg/m² paclitaxel administered by IV infusion on Days 1, 8, and 15 of a 28-day cycle.
Overall Number of Participants Analyzed	200
Geometric Mean (Geometric Coefficient of Variation) Unit of Measure: µg/mL
	193 (34%)

9.Secondary Outcome


Title	Cmax After 7th Ramucirumab (IMC-1211B) Infusion
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Cycle 4, Day 1, 1 hour post end of infusion (28-day cycles)

Outcome Measure Data

Analysis Population Description

All participants who received Ramucirumab (IMC-1121B) plus Paclitaxel and had Cmax observations at specific timepoint.


Arm/Group Title	Ramucirumab (IMC-1211B) Plus Paclitaxel
Arm/Group Description:	8 mg/kg of ramucirumab (IMC-1121B) ...
Arm/Group Description:	8 mg/kg of ramucirumab (IMC-1121B) was administered by IV infusion on Days 1 and 15 in combination with 80 mg/m² paclitaxel administered by IV infusion on Days 1, 8, and 15 of a 28-day cycle.
Overall Number of Participants Analyzed	127
Geometric Mean (Geometric Coefficient of Variation) Unit of Measure: µg/mL
	216 (30%)

10.Secondary Outcome


Title	Minimum Concentration (Cmin) Prior to First Ramucirumab (IMC-1211B) Infusion
Description	This outcome measure was included in error as the time point was befor...
Description	This outcome measure was included in error as the time point was before ramucirumab (IMC-1211B) was administered. Cmin was not analyzed.
Time Frame	Cycle 1, Day 1 predose (28-day cycles)

Outcome Measure Data

Analysis Population Description

Zero participants were analyzed.


Arm/Group Title	Ramucirumab (IMC-1211B) Plus Paclitaxel
Arm/Group Description:	8 mg/kg of ramucirumab (IMC-1121B) ...
Arm/Group Description:	8 mg/kg of ramucirumab (IMC-1121B) was administered by IV infusion on Days 1 and 15 in combination with 80 mg/m² paclitaxel administered by IV infusion on Days 1, 8, and 15 of a 28-day cycle.
Overall Number of Participants Analyzed	0

No data displayed because Outcome Measure has zero total analyzed.

11.Secondary Outcome


Title	Cmin Prior to 4th Ramucirumab (IMC-1211B) Infusion
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Cycle 2, Day 15 (28-day cycle)

Outcome Measure Data

Analysis Population Description

All participants who received Ramucirumab (IMC-1121B) plus Paclitaxel and had Cmin observations at specific timepoint.


Arm/Group Title	Ramucirumab (IMC-1211B) Plus Paclitaxel
Arm/Group Description:	8 mg/kg of ramucirumab (IMC-1121B) ...
Arm/Group Description:	8 mg/kg of ramucirumab (IMC-1121B) was administered by IV infusion on Days 1 and 15 in combination with 80 mg/m² paclitaxel administered by IV infusion on Days 1, 8, and 15 of a 28-day cycle.
Overall Number of Participants Analyzed	203
Geometric Mean (Geometric Coefficient of Variation) Unit of Measure: µg/mL
	45.0 (50%)

12.Secondary Outcome


Title	Cmin Prior to 7th Ramucirumab (IMC-1211B) Infusion
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Cycle 4, Day 1 (28-day cycles)

Outcome Measure Data

Analysis Population Description

All participants who received Ramucirumab (IMC-1121B) plus Paclitaxel and had Cmin observations at specific timepoint.


Arm/Group Title	Ramucirumab (IMC-1211B) Plus Paclitaxel
Arm/Group Description:	8 mg/kg of ramucirumab (IMC-1121B) ...
Arm/Group Description:	8 mg/kg of ramucirumab (IMC-1121B) was administered by IV infusion on Days 1 and 15 in combination with 80 mg/m² paclitaxel administered by IV infusion on Days 1, 8, and 15 of a 28-day cycle.
Overall Number of Participants Analyzed	142
Geometric Mean (Geometric Coefficient of Variation) Unit of Measure: µg/mL
	62.8 (47%)

13.Secondary Outcome


Title	Change From Baseline to End of Therapy in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life: Questionnaire (QLQ-C30) in Global Health Status
Description	EORTC QLQ-C30 v3.0 is a 30-item, self-administered questionnaire with ...
Description	EORTC QLQ-C30 v3.0 is a 30-item, self-administered questionnaire with multidimensional scales assessing 15 domains (5 functional domains [physical, role, cognitive, emotional, and social], 9 symptom scales [fatigue, pain, nausea and vomiting, dyspnea, loss of appetite, insomnia, constipation and diarrhea, and financial difficulties] and global health status scale). 28 questions assessed on a 1 (not at all) to 4 (very much) scale and the remaining 2 questions used a 1 (poor) to 7 (excellent) scale. A linear transformation was applied to standardize the raw scores to range between 0 and 100 per developer guidelines. For the functional domains and global health status scale, higher scores represent a better level of functioning. For symptoms scales, higher scores represented a greater degree of symptoms.
Time Frame	Baseline, end of therapy (up to 103 weeks)

Outcome Measure Data

Analysis Population Description

All participants according to the treatment group to which they were randomized with baseline and end of treatment Global Health Status observations.


Arm/Group Title	Ramucirumab (IMC-1211B) Plus Paclitaxel	Placebo Plus Paclitaxel
Arm/Group Description:	8 mg/kg of ramucirumab (IMC-1121B) ...	Placebo was administered by IV infu...
Arm/Group Description:	8 mg/kg of ramucirumab (IMC-1121B) was administered by IV infusion on Days 1 and 15 in combination with 80 mg/m² paclitaxel administered by IV infusion on Days 1, 8, and 15 of a 28-day cycle.	Placebo was administered by IV infusion on Days 1 and 15, in combination with 80 mg/m² paclitaxel administered on Days 1, 8, and 15 of a 28-day cycle.
Overall Number of Participants Analyzed	209	202
Mean (Standard Deviation) Unit of Measure: units on a scale
	-13.5 (23.24)	-12.1 (24.81)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramucirumab (IMC-1211B) Plus Paclitaxel, Placebo Plus Paclitaxel
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.3973
	Comments	Analysis of covariance (ANCOVA) included treatment group, randomization stratification factors and baseline value of Global Health Status scale.
	Method	ANCOVA
	Comments	[Not Specified]

14.Secondary Outcome


Title	Change From Baseline to End of Therapy in European Quality of Life Questionnaire-5 Dimension (EuroQol EQ-5D) Index Score
Description	The EQ-5D is a generic, multidimensional, health status instrument. Th...
Description	The EQ-5D is a generic, multidimensional, health status instrument. The profile allowed participants to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and mood using a 3-level scale [1 (no problem), 2 (some problems), and 3 (major problems)]. These combinations of responses were converted into a weighted health-state Index Score according to the United Kingdom (UK) population-based algorithm. The possible values for the Index Score ranged from -0.59 (severe problems in all 5 dimensions) to 1.0 (no problem in any dimension). A negative change indicated a worsening of the participant's health status.
Time Frame	Baseline, end of therapy (up to 103 weeks)

Outcome Measure Data

Analysis Population Description

All participants according to the treatment group to which they were randomized with baseline and end of treatment EQ-5D observations.


Arm/Group Title	Ramucirumab (IMC-1211B) Plus Paclitaxel	Placebo Plus Paclitaxel
Arm/Group Description:	8 mg/kg of ramucirumab (IMC-1121B) ...	Placebo was administered by IV infu...
Arm/Group Description:	8 mg/kg of ramucirumab (IMC-1121B) was administered by IV infusion on Days 1 and 15 in combination with 80 mg/m² paclitaxel administered by IV infusion on Days 1, 8, and 15 of a 28-day cycle.	Placebo was administered by IV infusion on Days 1 and 15, in combination with 80 mg/m² paclitaxel administered on Days 1, 8, and 15 of a 28-day cycle.
Overall Number of Participants Analyzed	205	201
Mean (Standard Deviation) Unit of Measure: units on a scale
	-0.16 (0.279)	-0.19 (0.337)

15.Other Pre-specified Outcome


Title	Number of Participants With Serious and Other Non-serious Adverse Events (AE) and Who Died
Description	Participants who died or who had clinically significant events defined...
Description	Participants who died or who had clinically significant events defined as serious AEs (SAEs) and other non-serious AEs (regardless of causality). A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.
Time Frame	Baseline up to 103 weeks and within 30 days of last dose of study drug

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and based on the treatment each participant received.


Arm/Group Title	Ramucirumab (IMC-1211B) Plus Paclitaxel	Placebo Plus Paclitaxel
Arm/Group Description:	8 mg/kg of ramucirumab (IMC-1121B) ...	Placebo was administered by IV infu...
Arm/Group Description:	8 mg/kg of ramucirumab (IMC-1121B) was administered by IV infusion on Days 1 and 15 in combination with 80 mg/m² paclitaxel administered by IV infusion on Days 1, 8, and 15 of a 28-day cycle.	Placebo was administered by IV infusion on Days 1 and 15, in combination with 80 mg/m² paclitaxel administered on Days 1, 8, and 15 of a 28-day cycle.
Overall Number of Participants Analyzed	327	329
Measure Type: Number Unit of Measure: participants
SAEs	161	146
Other Non-serious AEs	324	321
Died	37	52

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).

Arm/Group Title	Ramucirumab and Paclitaxel		Placebo and Paclitaxel
Arm/Group Description	8 mg/kg ramucirumab (IMC1121B) was ...		Placebo was administered by IV infu...
Arm/Group Description	8 mg/kg ramucirumab (IMC1121B) was administered by IV infusion on Days 1 and 15 in combination with 80 mg/m² administered by IV infusion on Days 1, 8, and 15 of a 28-day cycle.		Placebo was administered by IV infusion on Days 1 and 15, in combination with 80 mg/m² administered on Days 1, 8, and 15 of a 28-day cycle.
All-Cause Mortality
	Ramucirumab and Paclitaxel		Placebo and Paclitaxel
	Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events Serious Adverse Events
	Ramucirumab and Paclitaxel		Placebo and Paclitaxel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	161/327 (49.24%)		146/329 (44.38%)
Blood and lymphatic system disorders
Anaemia ^† 1	8/327 (2.45%)	8	7/329 (2.13%)	10
Disseminated intravascular coagulation ^† 1	0/327 (0.00%)	0	1/329 (0.30%)	1
Febrile neutropenia ^† 1	8/327 (2.45%)	8	5/329 (1.52%)	6
Leukopenia ^† 1	1/327 (0.31%)	1	1/329 (0.30%)	1
Neutropenia ^† 1	12/327 (3.67%)	17	4/329 (1.22%)	4
Cardiac disorders
Acute coronary syndrome ^† 1	0/327 (0.00%)	0	1/329 (0.30%)	1
Angina pectoris ^† 1	0/327 (0.00%)	0	1/329 (0.30%)	1
Atrial fibrillation ^† 1	3/327 (0.92%)	3	0/329 (0.00%)	0
Atrial flutter ^† 1	0/327 (0.00%)	0	1/329 (0.30%)	1
Atrial thrombosis ^† 1	0/327 (0.00%)	0	1/329 (0.30%)	1
Cardiac failure ^† 1	0/327 (0.00%)	0	1/329 (0.30%)	2
Extrasystoles ^† 1	0/327 (0.00%)	0	1/329 (0.30%)	1
Myocardial infarction ^† 1	0/327 (0.00%)	0	1/329 (0.30%)	1
Congenital, familial and genetic disorders
Pyloric stenosis ^† 1	0/327 (0.00%)	0	1/329 (0.30%)	1
Ear and labyrinth disorders
Hearing impaired ^† 1	1/327 (0.31%)	1	0/329 (0.00%)	0
Vertigo ^† 1	0/327 (0.00%)	0	1/329 (0.30%)	1
Endocrine disorders
Inappropriate antidiuretic hormone secretion ^† 1	1/327 (0.31%)	1	0/329 (0.00%)	0
Eye disorders
Cataract ^† 1	1/327 (0.31%)	1	0/329 (0.00%)	0
Lacrimation increased ^† 1	1/327 (0.31%)	1	0/329 (0.00%)	0
Gastrointestinal disorders
Abdominal pain ^† 1	10/327 (3.06%)	12	11/329 (3.34%)	12
Abdominal pain upper ^† 1	1/327 (0.31%)	1	0/329 (0.00%)	0
Anal haemorrhage ^† 1	1/327 (0.31%)	1	0/329 (0.00%)	0
Aphagia ^† 1	1/327 (0.31%)	1	0/329 (0.00%)	0
Ascites ^† 1	5/327 (1.53%)	8	3/329 (0.91%)	3
Constipation ^† 1	0/327 (0.00%)	0	2/329 (0.61%)	2
Diarrhoea ^† 1	5/327 (1.53%)	5	2/329 (0.61%)	2
Diverticular perforation ^† 1	1/327 (0.31%)	1	0/329 (0.00%)	0
Dysphagia ^† 1	4/327 (1.22%)	4	3/329 (0.91%)	3
Gastric haemorrhage ^† 1	3/327 (0.92%)	3	2/329 (0.61%)	2
Gastrointestinal haemorrhage ^† 1	4/327 (1.22%)	4	2/329 (0.61%)	2
Gastrointestinal obstruction ^† 1	0/327 (0.00%)	0	1/329 (0.30%)	1
Gastrointestinal perforation ^† 1	2/327 (0.61%)	3	0/329 (0.00%)	0
Haematemesis ^† 1	3/327 (0.92%)	3	0/329 (0.00%)	0
Ileus ^† 1	2/327 (0.61%)	3	0/329 (0.00%)	0
Ileus paralytic ^† 1	0/327 (0.00%)	0	1/329 (0.30%)	2
Intestinal ischaemia ^† 1	0/327 (0.00%)	0	1/329 (0.30%)	1
Intestinal obstruction ^† 1	6/327 (1.83%)	6	3/329 (0.91%)	3
Intestinal perforation ^† 1	1/327 (0.31%)	1	0/329 (0.00%)	0
Malabsorption ^† 1	1/327 (0.31%)	3	0/329 (0.00%)	0
Melaena ^† 1	2/327 (0.61%)	2	0/329 (0.00%)	0
Mouth ulceration ^† 1	1/327 (0.31%)	1	0/329 (0.00%)	0
Nausea ^† 1	2/327 (0.61%)	3	5/329 (1.52%)	6
Obstruction gastric ^† 1	1/327 (0.31%)	1	1/329 (0.30%)	1
Odynophagia ^† 1	1/327 (0.31%)	1	0/329 (0.00%)	0
Oesophageal food impaction ^† 1	0/327 (0.00%)	0	1/329 (0.30%)	1
Oesophageal haemorrhage ^† 1	1/327 (0.31%)	1	0/329 (0.00%)	0
Oesophageal perforation ^† 1	0/327 (0.00%)	0	1/329 (0.30%)	1
Oesophageal spasm ^† 1	1/327 (0.31%)	1	0/329 (0.00%)	0
Oesophageal stenosis ^† 1	0/327 (0.00%)	0	2/329 (0.61%)	2
Oesophageal ulcer ^† 1	0/327 (0.00%)	0	1/329 (0.30%)	1
Oesophagitis ^† 1	2/327 (0.61%)	2	0/329 (0.00%)	0
Pancreatitis acute ^† 1	1/327 (0.31%)	1	1/329 (0.30%)	1
Peritonitis ^† 1	5/327 (1.53%)	5	0/329 (0.00%)	0
Pneumatosis intestinalis ^† 1	1/327 (0.31%)	1	0/329 (0.00%)	0
Small intestinal obstruction ^† 1	3/327 (0.92%)	3	4/329 (1.22%)	5
Small intestinal stenosis ^† 1	0/327 (0.00%)	0	1/329 (0.30%)	1
Subileus ^† 1	1/327 (0.31%)	1	0/329 (0.00%)	0
Upper gastrointestinal haemorrhage ^† 1	1/327 (0.31%)	1	0/329 (0.00%)	0
Vomiting ^† 1	7/327 (2.14%)	9	10/329 (3.04%)	11
General disorders
Asthenia ^† 1	5/327 (1.53%)	7	0/329 (0.00%)	0
Chest pain ^† 1	1/327 (0.31%)	1	0/329 (0.00%)	0
Death ^† 1	1/327 (0.31%)	1	0/329 (0.00%)	0
Device dislocation ^† 1	0/327 (0.00%)	0	1/329 (0.30%)	1
Disease progression ^† 1	0/327 (0.00%)	0	2/329 (0.61%)	2
Drowning ^† 1	0/327 (0.00%)	0	1/329 (0.30%)	1
Fatigue ^† 1	5/327 (1.53%)	5	7/329 (2.13%)	9
Feeling abnormal ^† 1	0/327 (0.00%)	0	1/329 (0.30%)	1
General physical health deterioration ^† 1	8/327 (2.45%)	10	9/329 (2.74%)	12
Injection site injury ^† 1	1/327 (0.31%)	1	0/329 (0.00%)	0
Multi-organ failure ^† 1	0/327 (0.00%)	0	1/329 (0.30%)	1
Oedema peripheral ^† 1	3/327 (0.92%)	3	1/329 (0.30%)	1
Pain ^† 1	2/327 (0.61%)	2	0/329 (0.00%)	0
Pyrexia ^† 1	8/327 (2.45%)	9	7/329 (2.13%)	9
Hepatobiliary disorders
Bile duct obstruction ^† 1	1/327 (0.31%)	1	0/329 (0.00%)	0
Cholangitis ^† 1	1/327 (0.31%)	1	1/329 (0.30%)	1
Cholecystitis ^† 1	3/327 (0.92%)	3	0/329 (0.00%)	0
Cholecystitis acute ^† 1	2/327 (0.61%)	2	0/329 (0.00%)	0
Jaundice ^† 1	1/327 (0.31%)	1	0/329 (0.00%)	0
Jaundice cholestatic ^† 1	0/327 (0.00%)	0	1/329 (0.30%)	1
Infections and infestations
Anal abscess ^† 1	1/327 (0.31%)	1	0/329 (0.00%)	0
Appendicitis ^† 1	1/327 (0.31%)	1	0/329 (0.00%)	0
Bacteraemia ^† 1	0/327 (0.00%)	0	1/329 (0.30%)	1
Biliary sepsis ^† 1	1/327 (0.31%)	1	0/329 (0.00%)	0
Biliary tract infection ^† 1	0/327 (0.00%)	0	1/329 (0.30%)	1
Bronchopneumonia ^† 1	2/327 (0.61%)	2	0/329 (0.00%)	0
Cellulitis ^† 1	0/327 (0.00%)	0	2/329 (0.61%)	3
Device related infection ^† 1	2/327 (0.61%)	2	3/329 (0.91%)	3
Device related sepsis ^† 1	1/327 (0.31%)	1	0/329 (0.00%)	0
Diarrhoea infectious ^† 1	0/327 (0.00%)	0	1/329 (0.30%)	1
Endocarditis ^† 1	1/327 (0.31%)	1	1/329 (0.30%)	1
Herpes zoster ^† 1	1/327 (0.31%)	1	1/329 (0.30%)	1
Infection ^† 1	1/327 (0.31%)	1	0/329 (0.00%)	0
Influenza ^† 1	0/327 (0.00%)	0	1/329 (0.30%)	1
Lobar pneumonia ^† 1	1/327 (0.31%)	1	1/329 (0.30%)	1
Localised infection ^† 1	1/327 (0.31%)	1	0/329 (0.00%)	0
Lower respiratory tract infection ^† 1	0/327 (0.00%)	0	2/329 (0.61%)	3
Lung infection ^† 1	3/327 (0.92%)	6	0/329 (0.00%)	0
Neutropenic sepsis ^† 1	0/327 (0.00%)	0	1/329 (0.30%)	1
Perirectal abscess ^† 1	1/327 (0.31%)	1	1/329 (0.30%)	1
Peritonitis bacterial ^† 1	3/327 (0.92%)	3	0/329 (0.00%)	0
Pneumonia ^† 1	3/327 (0.92%)	3	3/329 (0.91%)	3
Pseudomonas infection ^† 1	1/327 (0.31%)	1	0/329 (0.00%)	0
Pulmonary sepsis ^† 1	0/327 (0.00%)	0	1/329 (0.30%)	2
Respiratory tract infection ^† 1	1/327 (0.31%)	1	0/329 (0.00%)	0
Sepsis ^† 1	5/327 (1.53%)	7	4/329 (1.22%)	5
Septic shock ^† 1	3/327 (0.92%)	3	1/329 (0.30%)	2
Staphylococcal infection ^† 1	0/327 (0.00%)	0	1/329 (0.30%)	1
Staphylococcal sepsis ^† 1	1/327 (0.31%)	1	0/329 (0.00%)	0
Urinary tract infection ^† 1	1/327 (0.31%)	1	1/329 (0.30%)	1
Urinary tract infection bacterial ^† 1	1/327 (0.31%)	1	0/329 (0.00%)	0
Urosepsis ^† 1	1/327 (0.31%)	1	0/329 (0.00%)	0
Viral infection ^† 1	1/327 (0.31%)	1	1/329 (0.30%)	1
Wound infection ^† 1	1/327 (0.31%)	1	0/329 (0.00%)	0
Injury, poisoning and procedural complications
Clavicle fracture ^† 1	1/327 (0.31%)	1	0/329 (0.00%)	0
Gastroenteritis radiation ^† 1	1/327 (0.31%)	1	0/329 (0.00%)	0
Incisional hernia ^† 1	1/327 (0.31%)	3	0/329 (0.00%)	0
Spinal compression fracture ^† 1	0/327 (0.00%)	0	1/329 (0.30%)	1
Splenic rupture ^† 1	1/327 (0.31%)	1	0/329 (0.00%)	0
Investigations
Alanine aminotransferase increased ^† 1	0/327 (0.00%)	0	1/329 (0.30%)	1
Anticoagulation drug level above therapeutic ^† 1	1/327 (0.31%)	1	0/329 (0.00%)	0
Aspartate aminotransferase increased ^† 1	0/327 (0.00%)	0	1/329 (0.30%)	1
Blood creatinine increased ^† 1	1/327 (0.31%)	2	0/329 (0.00%)	0
Blood urea increased ^† 1	1/327 (0.31%)	2	0/329 (0.00%)	0
Gamma-glutamyltransferase increased ^† 1	0/327 (0.00%)	0	1/329 (0.30%)	1
Metabolism and nutrition disorders
Cachexia ^† 1	0/327 (0.00%)	0	1/329 (0.30%)	2
Decreased appetite ^† 1	2/327 (0.61%)	4	5/329 (1.52%)	6
Dehydration ^† 1	6/327 (1.83%)	7	6/329 (1.82%)	7
Hypercalcaemia ^† 1	1/327 (0.31%)	1	0/329 (0.00%)	0
Hypoalbuminaemia ^† 1	0/327 (0.00%)	0	1/329 (0.30%)	1
Hyponatraemia ^† 1	3/327 (0.92%)	4	0/329 (0.00%)	0
Hypophagia ^† 1	1/327 (0.31%)	1	1/329 (0.30%)	1
Musculoskeletal and connective tissue disorders
Arthralgia ^† 1	1/327 (0.31%)	1	0/329 (0.00%)	0
Back pain ^† 1	1/327 (0.31%)	1	2/329 (0.61%)	2
Flank pain ^† 1	0/327 (0.00%)	0	1/329 (0.30%)	1
Myalgia ^† 1	0/327 (0.00%)	0	1/329 (0.30%)	1
Pain in extremity ^† 1	0/327 (0.00%)	0	1/329 (0.30%)	1
Pathological fracture ^† 1	0/327 (0.00%)	0	1/329 (0.30%)	2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Brain cancer metastatic ^† 1	1/327 (0.31%)	1	0/329 (0.00%)	0
Cancer pain ^† 1	1/327 (0.31%)	1	1/329 (0.30%)	1
Malignant ascites ^† 1	0/327 (0.00%)	0	1/329 (0.30%)	1
Malignant neoplasm progression ^† 1	48/327 (14.68%)	65	49/329 (14.89%)	66
Malignant pleural effusion ^† 1	0/327 (0.00%)	0	1/329 (0.30%)	1
Metastases to central nervous system ^† 1	0/327 (0.00%)	0	1/329 (0.30%)	1
Metastases to liver ^† 1	0/327 (0.00%)	0	1/329 (0.30%)	1
Metastases to meninges ^† 1	0/327 (0.00%)	0	1/329 (0.30%)	1
Metastases to spine ^† 1	0/327 (0.00%)	0	1/329 (0.30%)	1
Rectal cancer ^† 1	0/327 (0.00%)	0	1/329 (0.30%)	1
Tumour pain ^† 1	0/327 (0.00%)	0	1/329 (0.30%)	1
Nervous system disorders
Akathisia ^† 1	0/327 (0.00%)	0	1/329 (0.30%)	1
Cerebral haemorrhage ^† 1	0/327 (0.00%)	0	1/329 (0.30%)	2
Cerebral infarction ^† 1	1/327 (0.31%)	1	1/329 (0.30%)	1
Cerebrovascular accident ^† 1	1/327 (0.31%)	1	0/329 (0.00%)	0
Coma ^† 1	1/327 (0.31%)	1	0/329 (0.00%)	0
Hydrocephalus ^† 1	0/327 (0.00%)	0	1/329 (0.30%)	1
Intracranial pressure increased ^† 1	0/327 (0.00%)	0	1/329 (0.30%)	2
Ischaemic stroke ^† 1	1/327 (0.31%)	2	0/329 (0.00%)	0
Spinal cord compression ^† 1	0/327 (0.00%)	0	1/329 (0.30%)	1
Renal and urinary disorders
Azotaemia ^† 1	1/327 (0.31%)	1	0/329 (0.00%)	0
Dysuria ^† 1	1/327 (0.31%)	1	0/329 (0.00%)	0
Hydronephrosis ^† 1	2/327 (0.61%)	2	2/329 (0.61%)	2
Obstructive uropathy ^† 1	1/327 (0.31%)	1	0/329 (0.00%)	0
Renal failure ^† 1	2/327 (0.61%)	2	0/329 (0.00%)	0
Renal failure acute ^† 1	1/327 (0.31%)	1	2/329 (0.61%)	3
Urinary retention ^† 1	2/327 (0.61%)	2	1/329 (0.30%)	1
Reproductive system and breast disorders
Gynaecomastia ^† 1	1/226 (0.44%)	1	0/237 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome ^† 1	0/327 (0.00%)	0	1/329 (0.30%)	1
Aspiration ^† 1	0/327 (0.00%)	0	1/329 (0.30%)	1
Dyspnoea ^† 1	3/327 (0.92%)	3	4/329 (1.22%)	4
Haemoptysis ^† 1	2/327 (0.61%)	2	0/329 (0.00%)	0
Hypoxia ^† 1	1/327 (0.31%)	1	0/329 (0.00%)	0
Interstitial lung disease ^† 1	0/327 (0.00%)	0	3/329 (0.91%)	3
Lung infiltration ^† 1	1/327 (0.31%)	1	0/329 (0.00%)	0
Pleural effusion ^† 1	5/327 (1.53%)	5	4/329 (1.22%)	5
Pneumonitis ^† 1	1/327 (0.31%)	1	1/329 (0.30%)	1
Pneumothorax ^† 1	1/327 (0.31%)	1	1/329 (0.30%)	1
Pulmonary embolism ^† 1	2/327 (0.61%)	3	6/329 (1.82%)	8
Respiratory failure ^† 1	1/327 (0.31%)	1	0/329 (0.00%)	0
Vascular disorders
Arteriosclerosis ^† 1	1/327 (0.31%)	1	0/329 (0.00%)	0
Deep vein thrombosis ^† 1	2/327 (0.61%)	2	2/329 (0.61%)	2
Hypotension ^† 1	2/327 (0.61%)	3	0/329 (0.00%)	0
Hypovolaemic shock ^† 1	0/327 (0.00%)	0	1/329 (0.30%)	1
Vein disorder ^† 1	1/327 (0.31%)	1	0/329 (0.00%)	0
Vena cava thrombosis ^† 1	0/327 (0.00%)	0	1/329 (0.30%)	1
Venous thrombosis ^† 1	0/327 (0.00%)	0	2/329 (0.61%)	2
† Indicates events were collected by systematic assessment 1 Term from vocabulary, MedDRA 16.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Ramucirumab and Paclitaxel		Placebo and Paclitaxel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	324/327 (99.08%)		321/329 (97.57%)
Blood and lymphatic system disorders
Anaemia ^† 1	110/327 (33.64%)	261	116/329 (35.26%)	274
Leukopenia ^† 1	111/327 (33.94%)	471	69/329 (20.97%)	199
Neutropenia ^† 1	174/327 (53.21%)	878	102/329 (31.00%)	247
Thrombocytopenia ^† 1	43/327 (13.15%)	103	20/329 (6.08%)	37
Gastrointestinal disorders
Abdominal distension ^† 1	20/327 (6.12%)	27	20/329 (6.08%)	25
Abdominal pain ^† 1	98/327 (29.97%)	165	62/329 (18.84%)	104
Abdominal pain upper ^† 1	31/327 (9.48%)	48	35/329 (10.64%)	52
Ascites ^† 1	31/327 (9.48%)	46	25/329 (7.60%)	39
Constipation ^† 1	70/327 (21.41%)	95	71/329 (21.58%)	89
Diarrhoea ^† 1	105/327 (32.11%)	250	76/329 (23.10%)	126
Dysphagia ^† 1	17/327 (5.20%)	25	17/329 (5.17%)	18
Nausea ^† 1	114/327 (34.86%)	236	106/329 (32.22%)	183
Stomatitis ^† 1	64/327 (19.57%)	103	24/329 (7.29%)	33
Vomiting ^† 1	85/327 (25.99%)	142	65/329 (19.76%)	111
General disorders
Asthenia ^† 1	68/327 (20.80%)	179	45/329 (13.68%)	73
Fatigue ^† 1	128/327 (39.14%)	281	104/329 (31.61%)	209
Oedema peripheral ^† 1	82/327 (25.08%)	122	45/329 (13.68%)	57
Pyrexia ^† 1	56/327 (17.13%)	83	35/329 (10.64%)	53
Infections and infestations
Nasopharyngitis ^† 1	23/327 (7.03%)	34	19/329 (5.78%)	24
Urinary tract infection ^† 1	18/327 (5.50%)	22	11/329 (3.34%)	11
Investigations
Alanine aminotransferase increased ^† 1	20/327 (6.12%)	43	18/329 (5.47%)	22
Aspartate aminotransferase increased ^† 1	27/327 (8.26%)	62	17/329 (5.17%)	23
Weight decreased ^† 1	45/327 (13.76%)	79	49/329 (14.89%)	68
Metabolism and nutrition disorders
Decreased appetite ^† 1	131/327 (40.06%)	225	105/329 (31.91%)	172
Hypoalbuminaemia ^† 1	31/327 (9.48%)	47	13/329 (3.95%)	16
Hyponatraemia ^† 1	17/327 (5.20%)	23	9/329 (2.74%)	13
Musculoskeletal and connective tissue disorders
Arthralgia ^† 1	29/327 (8.87%)	54	20/329 (6.08%)	25
Back pain ^† 1	38/327 (11.62%)	48	39/329 (11.85%)	47
Myalgia ^† 1	34/327 (10.40%)	62	32/329 (9.73%)	44
Pain in extremity ^† 1	19/327 (5.81%)	21	10/329 (3.04%)	10
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm progression ^† 1	17/327 (5.20%)	17	26/329 (7.90%)	26
Nervous system disorders
Dizziness ^† 1	20/327 (6.12%)	25	13/329 (3.95%)	16
Dysgeusia ^† 1	29/327 (8.87%)	32	21/329 (6.38%)	23
Headache ^† 1	32/327 (9.79%)	50	22/329 (6.69%)	37
Neuropathy peripheral ^† 1	47/327 (14.37%)	88	30/329 (9.12%)	51
Paraesthesia ^† 1	24/327 (7.34%)	41	25/329 (7.60%)	41
Peripheral sensory neuropathy ^† 1	57/327 (17.43%)	122	36/329 (10.94%)	63
Polyneuropathy ^† 1	18/327 (5.50%)	31	22/329 (6.69%)	38
Psychiatric disorders
Insomnia ^† 1	31/327 (9.48%)	32	26/329 (7.90%)	27
Renal and urinary disorders
Proteinuria ^† 1	55/327 (16.82%)	156	20/329 (6.08%)	34
Respiratory, thoracic and mediastinal disorders
Cough ^† 1	41/327 (12.54%)	46	26/329 (7.90%)	35
Dysphonia ^† 1	17/327 (5.20%)	22	9/329 (2.74%)	13
Dyspnoea ^† 1	41/327 (12.54%)	61	31/329 (9.42%)	38
Epistaxis ^† 1	100/327 (30.58%)	157	23/329 (6.99%)	34
Skin and subcutaneous tissue disorders
Alopecia ^† 1	107/327 (32.72%)	137	127/329 (38.60%)	159
Dry skin ^† 1	25/327 (7.65%)	28	10/329 (3.04%)	10
Pruritus ^† 1	20/327 (6.12%)	23	11/329 (3.34%)	13
Rash ^† 1	35/327 (10.70%)	44	25/329 (7.60%)	28
Vascular disorders
Hypertension ^† 1	78/327 (23.85%)	155	16/329 (4.86%)	25
† Indicates events were collected by systematic assessment 1 Term from vocabulary, MedDRA 16.0

Limitations and Caveats

One (1) participant was randomized to the placebo/paclitaxel group but received ramucirumab in error. For ITT population this participant was included in placebo/paclitaxel group and for the Safety population included in the ramucirumab group.

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.

Investigators agreed to delay independently publishing or disclosing data, findings or conclusions from the study except as part of a multi-center publication. Upon study publication or if the draft publication is not produced within approximately 6 months of the final report of the study results, investigators may independently publish, subject to confidential information review/redaction by sponsor. The sponsor may request publication delay up to 90 days to seek patent protection.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Chief Medical Officer
Organization:	Eli Lilly and Company
Phone:	800-545-5979

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

Mitani S, Chen Y, Inoue K, Mori J, Gao L, Long A, Wakabayashi S. Clinical Impact of a Shortened Infusion Duration of Ramucirumab in Japanese Patients -A Model-Based Approach. Gan To Kagaku Ryoho. 2021 Nov;48(11):1381-1387.

Yamaguchi K, Shimada Y, Hironaka S, Sugimoto N, Komatsu Y, Nishina T, Omuro Y, Tamura T, Piao Y, Homma G, Jen MH, Liepa AM, Muro K. Quality of Life Associated with Ramucirumab Treatment in Patients with Advanced Gastric Cancer in Japan: Exploratory Analysis from the Phase III RAINBOW Trial. Clin Drug Investig. 2021 Jan;41(1):53-64. doi: 10.1007/s40261-020-00979-3. Epub 2020 Dec 23.

Cascinu S, Bodoky G, Muro K, Van Cutsem E, Oh SC, Folprecht G, Ananda S, Girotto G, Wainberg ZA, Miron MLL, Ajani J, Wei R, Liepa AM, Carlesi R, Emig M, Ohtsu A. Tumor Response and Symptom Palliation from RAINBOW, a Phase III Trial of Ramucirumab Plus Paclitaxel in Previously Treated Advanced Gastric Cancer. Oncologist. 2021 Mar;26(3):e414-e424. doi: 10.1002/onco.13623. Epub 2020 Dec 23.

De Vita F, Borg C, Farina G, Geva R, Carton I, Cuku H, Wei R, Muro K. Ramucirumab and paclitaxel in patients with gastric cancer and prior trastuzumab: subgroup analysis from RAINBOW study. Future Oncol. 2019 Aug;15(23):2723-2731. doi: 10.2217/fon-2019-0243. Epub 2019 Jun 25. Erratum In: Future Oncol. 2021 Sep;17(25):3409.

Chau I, Fuchs CS, Ohtsu A, Barzi A, Liepa AM, Cui ZL, Hsu Y, Al-Batran SE. Association of quality of life with disease characteristics and treatment outcomes in patients with advanced gastric cancer: Exploratory analysis of RAINBOW and REGARD phase III trials. Eur J Cancer. 2019 Jan;107:115-123. doi: 10.1016/j.ejca.2018.11.013. Epub 2018 Dec 14.

Tabernero J, Ohtsu A, Muro K, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, Hironaka S, Ajani JA, Tomasek J, Safran H, Chandrawansa K, Hsu Y, Heathman M, Khan A, Ni L, Melemed AS, Gao L, Ferry D, Fuchs CS. Exposure-Response Analyses of Ramucirumab from Two Randomized, Phase III Trials of Second-line Treatment for Advanced Gastric or Gastroesophageal Junction Cancer. Mol Cancer Ther. 2017 Oct;16(10):2215-2222. doi: 10.1158/1535-7163.MCT-16-0895. Epub 2017 Jul 17.

Al-Batran SE, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, Hironaka S, Sugimoto N, Lipatov ON, Kim TY, Cunningham D, Rougier P, Muro K, Liepa AM, Chandrawansa K, Emig M, Ohtsu A, Wilke H. Quality-of-life and performance status results from the phase III RAINBOW study of ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated gastric or gastroesophageal junction adenocarcinoma. Ann Oncol. 2016 Apr;27(4):673-9. doi: 10.1093/annonc/mdv625. Epub 2016 Jan 7.

Shitara K, Muro K, Shimada Y, Hironaka S, Sugimoto N, Komatsu Y, Nishina T, Yamaguchi K, Segawa Y, Omuro Y, Tamura T, Doi T, Yukisawa S, Yasui H, Nagashima F, Gotoh M, Esaki T, Emig M, Chandrawansa K, Liepa AM, Wilke H, Ichimiya Y, Ohtsu A. Subgroup analyses of the safety and efficacy of ramucirumab in Japanese and Western patients in RAINBOW: a randomized clinical trial in second-line treatment of gastric cancer. Gastric Cancer. 2016 Jul;19(3):927-38. doi: 10.1007/s10120-015-0559-z. Epub 2015 Oct 28.

Wilke H, Muro K, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, Hironaka S, Sugimoto N, Lipatov O, Kim TY, Cunningham D, Rougier P, Komatsu Y, Ajani J, Emig M, Carlesi R, Ferry D, Chandrawansa K, Schwartz JD, Ohtsu A; RAINBOW Study Group. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol. 2014 Oct;15(11):1224-35. doi: 10.1016/S1470-2045(14)70420-6. Epub 2014 Sep 17.

Layout table for additonal information

Responsible Party:	Eli Lilly and Company
ClinicalTrials.gov Identifier:	NCT01170663
Other Study ID Numbers:	13894 I4T-IE-JVBE ( Other Identifier: Eli Lilly and Company ) CP12-0922 ( Other Identifier: ImClone Systems ) 2010-020426-18 ( EudraCT Number )
First Submitted:	July 21, 2010
First Posted:	July 27, 2010
Results First Submitted:	July 1, 2014
Results First Posted:	July 31, 2014
Last Update Posted:	September 18, 2019

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