Study of IMC-1121B (Ramucirumab) With Best Supportive Care in Participants With Gastric Cancer and Adenocarcinoma

• ClinicalTrials.gov Identifier: NCT00917384
• Recruitment Status: Completed
• First Posted: June 10, 2009
• Results First Posted: October 16, 2014
• Last Update Posted: September 25, 2019
• 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: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Conditions: Gastric Cancer; Adenocarcinoma
• Interventions: Biological: ramucirumab; Drug: Placebo; Other: Best Supportive Care (BSC)
• Enrollment: 355

Participant Flow

Recruitment Details
Pre-assignment Details	In the Participant Flow participants who completed were those who died due to any cause or were alive and on study at conclusion but off treatment.

Arm/Group Title	IMC-1121B (Ramucirumab )	Placebo
Arm/Group Description	Participants received IMC-1121B (ramucirumab), administered via intravenous infusion every 2 weeks at a dose of 8 milligrams/kilogram (mg/kg), plus best supportive care (BSC) as determined appropriate by the investigator(s). Treatment continued until there was evidence of progressive disease (PD), the development of unacceptable toxicity, protocol noncompliance, or withdrawal of consent.	Participants received placebo by intravenous infusion every 2 weeks plus BSC as determined appropriate by the investigator(s). Because investigators and ancillary medical personnel were blinded as to assignment to active therapy versus placebo, the volume of placebo administered was calculated as if it were active product with a dose of 8 mg/kg. Treatment continued until there was evidence of PD, the development of unacceptable toxicity, protocol noncompliance, or withdrawal of consent.
Period Title: Overall Study
Started	238	117
Received at Least 1 Dose of Study Drug	236	115
Completed	224	113
Not Completed	14	4
Reason Not Completed
Lost to Follow-up	4	2
Withdrawal by Subject	10	2

Baseline Characteristics

Arm/Group Title		IMC-1121B (Ramucirumab)	Placebo	Total
Arm/Group Description		Participants received IMC-1121B (ramucirumab), administered via intravenous infusion every 2 weeks at a dose of 8 milligrams/kilogram (mg/kg), plus best supportive care (BSC) as determined by the investigator(s). Treatment continued until there was evidence of progressive disease (PD), the development of unacceptable toxicity, protocol noncompliance, or withdrawal of consent.	Participants received placebo by intravenous infusion every 2 weeks plus best supportive care as determined appropriate by the investigator(s). Because investigators and ancillary medical personnel were blinded as to assignment to active therapy versus placebo, the volume of placebo administered was calculated as if it were active product with a dose of 8 mg/kg. Treatment continued until there was evidence of PD, the development of unacceptable toxicity, protocol noncompliance, or withdrawal of consent.	Total of all reporting groups
Overall Number of Baseline Participants		238	117	355
Baseline Analysis Population Description		All randomized participants.
Age, Continuous; Median (Full Range); Unit of measure: Years
	Number Analyzed	238 participants	117 participants	355 participants
		60.0; (30 to 86)	60.0; (24 to 87)	60.0; (24 to 87)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	238 participants	117 participants	355 participants
	Female	69 29.0%	38 32.5%	107 30.1%
	Male	169 71.0%	79 67.5%	248 69.9%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	238 participants	117 participants	355 participants
	Hispanic or Latino	41 17.2%	19 16.2%	60 16.9%
	Not Hispanic or Latino	197 82.8%	98 83.8%	295 83.1%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants	Number Analyzed	238 participants	117 participants	355 participants
Argentina		4	2	6
Australia		8	4	12
Bosnia and Herzegovina		1	3	4
Brazil		24	14	38
Canada		8	2	10
Chile		1	1	2
Colombia		2	1	3
Czech Republic		24	13	37
Egypt		1	0	1
Spain		12	4	16
United Kingdom		13	4	17
Guatemala		6	2	8
Croatia		7	0	7
Indonesia		2	1	3
India		16	8	24
Italy		23	11	34
Korea, Republic of		11	6	17
Lebanon		1	0	1
Malta		2	3	5
New Zealand		1	1	2
Philippines		1	1	2
Poland		9	4	13
Romania		13	4	17
Russian Federation		14	8	22
Thailand		1	0	1
Turkey		5	1	6
Taiwan		3	0	3
United States		25	18	43
South Africa		0	1	1
Race; Measure Type: Number; Unit of measure: Participants	Number Analyzed	238 participants	117 participants	355 participants
White		181	91	272
Asian		39	17	56
Black		4	2	6
Other		14	7	21

Outcome Measures

1. Primary Outcome

Title	Overall Survival (OS)
Description	Overall survival is defined as the time from the date of randomization to the date of death from any cause. Participants who were alive at the date of data cut-off or who were lost to follow-up were censored on the last date the participant was known to be alive
Time Frame	Randomization up to 28 months post-randomization

Outcome Measure Data

Analysis Population Description

Intent-to-treat population: all randomized participants. Censored participants: ramucirumab=59, placebo=18.

Arm/Group Title	IMC-1121B (Ramucirumab)	Placebo
Arm/Group Description:	Participants received IMC-1121B (ramucirumab), administered via intravenous infusion every 2 weeks at a dose of 8 milligrams/kilogram (mg/kg), plus best supportive care (BSC) as determined by the investigator(s). Treatment continued until there was evidence of progressive disease (PD), the development of unacceptable toxicity, protocol noncompliance, or withdrawal of consent.	Participants received placebo by intravenous infusion every 2 weeks plus best supportive care as determined appropriate by the investigator(s). Because investigators and ancillary medical personnel were blinded as to assignment to active therapy versus placebo, the volume of placebo administered was calculated as if it were active product with a dose of 8 mg/kg. Treatment continued until there was evidence of PD, the development of unacceptable toxicity, protocol noncompliance, or withdrawal of consent.
Overall Number of Participants Analyzed	238	117
Median (95% Confidence Interval); Unit of Measure: months
	5.2; (4.4 to 5.7)	3.8; (2.8 to 4.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IMC-1121B (Ramucirumab), Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0473
	Comments	[Not Specified]
	Method	Stratified Log-Rank Test
	Comments	Stratified Log-Rank Test and HR stratified by randomization strata (weight loss over the prior 3 months, primary tumor site and geographical region).
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.776
	Confidence Interval	95%; 0.603 to 0.998
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Progression-Free Survival (PFS)
Description	PFS is defined as the time from date of randomization until date of objectively determined progressive disease (PD) or death due to any cause, whichever is first. Participants alive and without PD were censored at the time of last adequate objective tumor assessment (that is, response other than unevaluable).
Time Frame	Randomization up to 17 months

Outcome Measure Data

Analysis Population Description

Intent-to-treat population: all randomized participants. Censored participants: ramucirumab=39, placebo=9.

Arm/Group Title	IMC-1121B (Ramucirumab)	Placebo
Arm/Group Description:	Participants received IMC-1121B (ramucirumab), administered via intravenous infusion every 2 weeks at a dose of 8 milligrams/kilogram (mg/kg), plus best supportive care (BSC) as determined by the investigator(s). Treatment continued until there was evidence of progressive disease (PD), the development of unacceptable toxicity, protocol noncompliance, or withdrawal of consent.	Participants received placebo by intravenous infusion every 2 weeks plus best supportive care as determined appropriate by the investigator(s). Because investigators and ancillary medical personnel were blinded as to assignment to active therapy versus placebo, the volume of placebo administered was calculated as if it were active product with a dose of 8 mg/kg. Treatment continued until there was evidence of PD, the development of unacceptable toxicity, protocol noncompliance, or withdrawal of consent.
Overall Number of Participants Analyzed	238	117
Median (95% Confidence Interval); Unit of Measure: months
	2.1; (1.5 to 2.7)	1.3; (1.3 to 1.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IMC-1121B (Ramucirumab), Placebo
	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	Stratified Log-Rank Test and HR stratified by randomization strata (weight loss over the prior 3 months, primary tumor site and geographical region).
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.483
	Confidence Interval	(2-Sided) 95%; 0.376 to 0.620
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	Percentage of Participants Who Are Progression-Free at Week 12 (PFS Rate)
Description	The percentage of participants alive and progression-free 12 weeks after randomization. Progression-free survival (PFS) is defined as the time from the date of randomization until the date of objectively determined progressive disease (PD) or death due to any cause whichever comes first. Participants alive and without PD were censored at the time of the last adequate objective tumor assessment.
Time Frame	Week 12 post-randomization

Outcome Measure Data

Analysis Population Description

Intent-to-treat population: all randomized participants.

Arm/Group Title	IMC-1121B (Ramucirumab)	Placebo
Arm/Group Description:	Participants received IMC-1121B (ramucirumab), administered via intravenous infusion every 2 weeks at a dose of 8 milligrams/kilogram (mg/kg), plus best supportive care (BSC) as determined by the investigator(s). Treatment continued until there was evidence of progressive disease (PD), the development of unacceptable toxicity, protocol noncompliance, or withdrawal of consent.	Participants received placebo by intravenous infusion every 2 weeks plus best supportive care as determined appropriate by the investigator(s). Because investigators and ancillary medical personnel were blinded as to assignment to active therapy versus placebo, the volume of placebo administered was calculated as if it were active product with a dose of 8 mg/kg. Treatment continued until there was evidence of PD, the development of unacceptable toxicity, protocol noncompliance, or withdrawal of consent.
Overall Number of Participants Analyzed	238	117
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	40.1; (33.6 to 46.4)	15.8; (9.7 to 23.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IMC-1121B (Ramucirumab), Placebo
	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	Normal Approximation
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference Between Arms
	Estimated Value	24.2
	Confidence Interval	(2-Sided) 95%; 14.9 to 33.6
	Estimation Comments	[Not Specified]

4. Secondary Outcome

Title	Percentage of Participants With Objective Response (Objective Response Rate [ORR])
Description	ORR is equal to the percentage of participants achieving a best overall response of complete response (CR) or partial response (PR). CR and PR were defined using the Response Evaluation Criteria in Solid Tumors (RECIST v1.0). CR is defined as the disappearance of all target and non-target lesions, no appearance of new lesions and confirmed at the consecutive tumor assessment. PR is 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, no appearance of new lesions and confirmed at a subsequent tumor assessment.
Time Frame	Randomization up to 17 months post-randomization

Outcome Measure Data

Analysis Population Description

Intent-to-treat population: all randomized participants.

Arm/Group Title	IMC-1121B (Ramucirumab)	Placebo
Arm/Group Description:	Participants received IMC-1121B (ramucirumab), administered via intravenous infusion every 2 weeks at a dose of 8 milligrams/kilogram (mg/kg), plus best supportive care (BSC) as determined by the investigator(s). Treatment continued until there was evidence of progressive disease (PD), the development of unacceptable toxicity, protocol noncompliance, or withdrawal of consent.	Participants received placebo by intravenous infusion every 2 weeks plus best supportive care as determined appropriate by the investigator(s). Because investigators and ancillary medical personnel were blinded as to assignment to active therapy versus placebo, the volume of placebo administered was calculated as if it were active product with a dose of 8 mg/kg. Treatment continued until there was evidence of PD, the development of unacceptable toxicity, protocol noncompliance, or withdrawal of consent.
Overall Number of Participants Analyzed	238	117
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	3.4; (1.5 to 6.5)	2.6; (0.5 to 7.3)

5. Secondary Outcome

Title	Duration of Response (DOR)
Description	DOR is the interval from date of initial documented response (complete response [CR] or partial response [PR]) to first documented date of disease progression (PD) or death as a result of any cause. CR and PR were defined using the Response Evaluation Criteria in Solid Tumors (RECIST v1.0). CR is defined as the disappearance of all target and non-target lesions, no appearance of new lesions and confirmed at the consecutive tumor assessment. PR is 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, no appearance of new lesions and confirmed at a subsequent tumor assessment. Participants who did not relapse or die were censored at the time of the last adequate objective tumor assessment.
Time Frame	Randomization up to 17 months post-randomization

Outcome Measure Data

Analysis Population Description

Zero participants were analyzed. The number of all responders (participants with CR or PR) was too small for a meaningful analysis, as specified in the statistical analysis plan.

Arm/Group Title	IMC-1121B (Ramucirumab)	Placebo
Arm/Group Description:	Participants received IMC-1121B (ramucirumab), administered via intravenous infusion every 2 weeks at a dose of 8 milligrams/kilogram (mg/kg), plus best supportive care (BSC) as determined by the investigator(s). Treatment continued until there was evidence of progressive disease (PD), the development of unacceptable toxicity, protocol noncompliance, or withdrawal of consent.	Participants received placebo by intravenous infusion every 2 weeks plus best supportive care as determined appropriate by the investigator(s). Because investigators and ancillary medical personnel were blinded as to assignment to active therapy versus placebo, the volume of placebo administered was calculated as if it were active product with a dose of 8 mg/kg. Treatment continued until there was evidence of PD, the development of unacceptable toxicity, protocol noncompliance, or withdrawal of consent.
Overall Number of Participants Analyzed	0	0

No data displayed because Outcome Measure has zero total analyzed.

6. Secondary Outcome

Title	Change From Baseline in Quality of Life (QoL) as Measured by the European Organisation for Research and Treatment of Cancer Questionnaire (EORTC-QLQ-C30)
Description	EORTC QLQ-C30 v3.0 is a self-administered questionnaire with multidimensional scales that measures 5 functional domains (physical, role, cognitive, emotional, and social), global health status, and symptom scales of fatigue, pain, nausea and vomiting, dyspnea, loss of appetite, insomnia, constipation and 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, higher scores represent a better level of functioning. For symptoms scales, higher scores represented a greater degree of symptoms. Best change from baseline results determined by Least Square (LS) mean estimated with randomization stratification factors and baseline value as continuous covariate.
Time Frame	Baseline up to Cycle 10 (18 weeks [1 cycle=2 weeks])

Outcome Measure Data

Analysis Population Description

All randomized participants with EORTC QLQ-C30 values at baseline and any point up to 18 weeks post-baseline.

Arm/Group Title	IMC-1121B (Ramucirumab)	Placebo
Arm/Group Description:	Participants received IMC-1121B (ramucirumab), administered via intravenous infusion every 2 weeks at a dose of 8 milligrams/kilogram (mg/kg), plus best supportive care (BSC) as determined by the investigator(s). Treatment continued until there was evidence of progressive disease (PD), the development of unacceptable toxicity, protocol noncompliance, or withdrawal of consent.	Participants received placebo by intravenous infusion every 2 weeks plus best supportive care as determined appropriate by the investigator(s). Because investigators and ancillary medical personnel were blinded as to assignment to active therapy versus placebo, the volume of placebo administered was calculated as if it were active product with a dose of 8 mg/kg. Treatment continued until there was evidence of PD, the development of unacceptable toxicity, protocol noncompliance, or withdrawal of consent.
Overall Number of Participants Analyzed	114	26
Least Squares Mean (Standard Error); Unit of Measure: units on a scale
Global Health Status/QoL	2.42 (2.99)	0.80 (4.48)
Physical Functioning	-6.26 (3.20)	-12.01 (4.82)
Role Functioning	-4.32 (4.65)	-11.79 (6.99)
Emotional Functioning	-1.61 (3.29)	-6.51 (4.92)
Cognitive Functioning	-4.26 (2.63)	-10.94 (3.94)
Social Functioning	-1.98 (3.90)	-1.37 (5.86)
Fatigue	3.16 (3.43)	6.88 (5.16)
Nausea and Vomiting	1.77 (2.86)	2.88 (4.32)
Pain	0.13 (3.61)	3.85 (5.42)
Dyspnea	-2.61 (3.35)	3.51 (5.08)
Insomnia	-7.47 (4.19)	-3.95 (6.28)
Appetite Loss	-1.01 (4.60)	7.16 (6.91)
Constipation	0.09 (3.79)	7.94 (5.69)
Diarrhea	-3.97 (1.64)	-5.49 (2.46)
Financial Difficulties	-12.86 (3.78)	-2.39 (5.68)

7. Secondary Outcome

Title	Number of Participants With Adverse Events
Description	Clinically significant events were defined as serious adverse events (SAE) and other treatment-emergent non-serious adverse events (NSAE). A summary of SAEs and all other NSAEs is located in the Reported Adverse Event module.
Time Frame	Randomization up to 18 months

Outcome Measure Data

Analysis Population Description

Safety Population: All randomized participants who received at least 1 dose of study drug.

Arm/Group Title	IMC-1121B (Ramucirumab)	Placebo
Arm/Group Description:	Participants received IMC-1121B (ramucirumab), administered via intravenous infusion every 2 weeks at a dose of 8 milligrams/kilogram (mg/kg), plus best supportive care (BSC) as determined by the investigator(s). Treatment continued until there was evidence of progressive disease (PD), the development of unacceptable toxicity, protocol noncompliance, or withdrawal of consent.	Participants received placebo by intravenous infusion every 2 weeks plus best supportive care as determined appropriate by the investigator(s). Because investigators and ancillary medical personnel were blinded as to assignment to active therapy versus placebo, the volume of placebo administered was calculated as if it were active product with a dose of 8 mg/kg. Treatment continued until there was evidence of PD, the development of unacceptable toxicity, protocol noncompliance, or withdrawal of consent.
Overall Number of Participants Analyzed	236	115
Measure Type: Number; Unit of Measure: participants
Participants with SAE	112	51
Participants with ≥ 1 treatment emergent NSAE	213	91

8. Secondary Outcome

Title	Maximum Concentration (Cmax) of IMC-1121B
Description	Cmax was not analyzed as only pre-dose samples were collected.
Time Frame	6 weeks post-randomization

Outcome Measure Data

Analysis Population Description

Zero participants were analyzed.

Arm/Group Title	IMC-1121B (Ramucirumab)	Placebo
Arm/Group Description:	Participants received IMC-1121B (ramucirumab), administered via intravenous infusion every 2 weeks at a dose of 8 milligrams/kilogram (mg/kg), plus best supportive care (BSC) as determined by the investigator(s). Treatment continued until there was evidence of progressive disease (PD), the development of unacceptable toxicity, protocol noncompliance, or withdrawal of consent.	Participants received placebo by intravenous infusion every 2 weeks plus best supportive care as determined appropriate by the investigator(s). Because investigators and ancillary medical personnel were blinded as to assignment to active therapy versus placebo, the volume of placebo administered was calculated as if it were active product with a dose of 8 mg/kg. Treatment continued until there was evidence of PD, the development of unacceptable toxicity, protocol noncompliance, or withdrawal of consent.
Overall Number of Participants Analyzed	0	0

No data displayed because Outcome Measure has zero total analyzed.

9. Secondary Outcome

Title	Number of Participants Who Developed Antibodies Against IMC-1121B
Description	The number of participants who developed treatment emergent antibody responses to IMC-1121B after baseline.
Time Frame	Baseline, 12 Weeks

Outcome Measure Data

Analysis Population Description

Subset of the Safety Population: All randomized participants who received at least 1 dose of study drug and who had immunogenicity analysis performed.

Arm/Group Title	IMC-1121B (Ramucirumab)	Placebo
Arm/Group Description:	Participants received IMC-1121B (ramucirumab), administered via intravenous infusion every 2 weeks at a dose of 8 milligrams/kilogram (mg/kg), plus best supportive care (BSC) as determined by the investigator(s). Treatment continued until there was evidence of progressive disease (PD), the development of unacceptable toxicity, protocol noncompliance, or withdrawal of consent.	Participants received placebo by intravenous infusion every 2 weeks plus best supportive care as determined appropriate by the investigator(s). Because investigators and ancillary medical personnel were blinded as to assignment to active therapy versus placebo, the volume of placebo administered was calculated as if it were active product with a dose of 8 mg/kg. Treatment continued until there was evidence of PD, the development of unacceptable toxicity, protocol noncompliance, or withdrawal of consent.
Overall Number of Participants Analyzed	207	106
Measure Type: Number; Unit of Measure: participants
	6	1

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	IMC-1121B (Ramucirumab)		Placebo
Arm/Group Description	Participants received IMC-1121B (ramucirumab), administered via intravenous infusion every 2 weeks at a dose of 8 milligrams/kilogram (mg/kg), plus best supportive care (BSC) as determined by the investigator(s). Treatment continued until there was evidence of progressive disease (PD), the development of unacceptable toxicity, protocol noncompliance, or withdrawal of consent.		Participants received placebo by intravenous infusion every 2 weeks plus best supportive care as determined appropriate by the investigator(s). Because investigators and ancillary medical personnel were blinded as to assignment to active therapy versus placebo, the volume of placebo administered was calculated as if it were active product with a dose of 8 mg/kg. Treatment continued until there was evidence of PD, the development of unacceptable toxicity, protocol noncompliance, or withdrawal of consent.
All-Cause Mortality
	IMC-1121B (Ramucirumab)		Placebo
	Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events
	IMC-1121B (Ramucirumab)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	112/236 (47.46%)		51/115 (44.35%)
Blood and lymphatic system disorders
Anaemia † 1	11/236 (4.66%)	11	2/115 (1.74%)	4
Disseminated intravascular coagulation † 1	1/236 (0.42%)	1	0/115 (0.00%)	0
Febrile neutropenia † 1	1/236 (0.42%)	1	0/115 (0.00%)	0
Pancytopenia † 1	0/236 (0.00%)	0	2/115 (1.74%)	2
Thrombocytopenia † 1	1/236 (0.42%)	1	2/115 (1.74%)	2
Cardiac disorders
Cardiac arrest † 1	1/236 (0.42%)	1	0/115 (0.00%)	0
Myocardial infarction † 1	1/236 (0.42%)	1	0/115 (0.00%)	0
Sinus bradycardia † 1	0/236 (0.00%)	0	1/115 (0.87%)	1
Endocrine disorders
Inappropriate antidiuretic hormone secretion † 1	1/236 (0.42%)	1	0/115 (0.00%)	0
Gastrointestinal disorders
Abdominal distension † 1	1/236 (0.42%)	1	1/115 (0.87%)	1
Abdominal pain † 1	10/236 (4.24%)	11	3/115 (2.61%)	3
Abdominal pain upper † 1	1/236 (0.42%)	1	0/115 (0.00%)	0
Ascites † 1	6/236 (2.54%)	6	3/115 (2.61%)	4
Colonic obstruction † 1	0/236 (0.00%)	0	1/115 (0.87%)	1
Constipation † 1	0/236 (0.00%)	0	2/115 (1.74%)	2
Diarrhoea † 1	0/236 (0.00%)	0	2/115 (1.74%)	2
Dyspepsia † 1	0/236 (0.00%)	0	1/115 (0.87%)	1
Dysphagia † 1	6/236 (2.54%)	6	3/115 (2.61%)	4
Gastric haemorrhage † 1	1/236 (0.42%)	1	1/115 (0.87%)	1
Gastrointestinal haemorrhage † 1	2/236 (0.85%)	2	2/115 (1.74%)	3
Gastrointestinal obstruction † 1	0/236 (0.00%)	0	1/115 (0.87%)	1
Haematemesis † 1	3/236 (1.27%)	3	0/115 (0.00%)	0
Ileus † 1	1/236 (0.42%)	1	0/115 (0.00%)	0
Intestinal obstruction † 1	5/236 (2.12%)	5	0/115 (0.00%)	0
Intestinal perforation † 1	1/236 (0.42%)	1	0/115 (0.00%)	0
Large intestine perforation † 1	1/236 (0.42%)	1	1/115 (0.87%)	1
Nausea † 1	3/236 (1.27%)	3	0/115 (0.00%)	0
Obstruction gastric † 1	2/236 (0.85%)	2	1/115 (0.87%)	1
Oesophageal fistula † 1	0/236 (0.00%)	0	1/115 (0.87%)	1
Oesophageal obstruction † 1	1/236 (0.42%)	1	0/115 (0.00%)	0
Oesophageal stenosis † 1	1/236 (0.42%)	1	0/115 (0.00%)	0
Proctalgia † 1	0/236 (0.00%)	0	1/115 (0.87%)	1
Small intestinal obstruction † 1	2/236 (0.85%)	3	0/115 (0.00%)	0
Upper gastrointestinal haemorrhage † 1	1/236 (0.42%)	1	1/115 (0.87%)	1
Vomiting † 1	7/236 (2.97%)	7	5/115 (4.35%)	5
General disorders
Asthenia † 1	0/236 (0.00%)	0	4/115 (3.48%)	4
Chest pain † 1	1/236 (0.42%)	1	0/115 (0.00%)	0
Death † 1	5/236 (2.12%)	5	0/115 (0.00%)	0
Device dislocation † 1	0/236 (0.00%)	0	1/115 (0.87%)	1
Disease progression † 1	10/236 (4.24%)	10	8/115 (6.96%)	8
Extravasation † 1	1/236 (0.42%)	1	0/115 (0.00%)	0
Fatigue † 1	2/236 (0.85%)	2	1/115 (0.87%)	1
General physical health deterioration † 1	4/236 (1.69%)	4	0/115 (0.00%)	0
Mucosal inflammation † 1	1/236 (0.42%)	1	0/115 (0.00%)	0
Multi-organ failure † 1	6/236 (2.54%)	6	1/115 (0.87%)	1
Pain † 1	2/236 (0.85%)	2	0/115 (0.00%)	0
Pyrexia † 1	0/236 (0.00%)	0	1/115 (0.87%)	1
Sudden death † 1	0/236 (0.00%)	0	1/115 (0.87%)	1
Systemic inflammatory response syndrome † 1	1/236 (0.42%)	1	0/115 (0.00%)	0
Hepatobiliary disorders
Bile duct obstruction † 1	1/236 (0.42%)	1	1/115 (0.87%)	1
Cholangitis † 1	1/236 (0.42%)	1	1/115 (0.87%)	1
Cholecystitis acute † 1	2/236 (0.85%)	2	0/115 (0.00%)	0
Cholestasis † 1	1/236 (0.42%)	1	0/115 (0.00%)	0
Hyperbilirubinaemia † 1	0/236 (0.00%)	0	1/115 (0.87%)	1
Jaundice cholestatic † 1	1/236 (0.42%)	1	0/115 (0.00%)	0
Liver disorder † 1	1/236 (0.42%)	1	0/115 (0.00%)	0
Infections and infestations
Abscess † 1	0/236 (0.00%)	0	1/115 (0.87%)	1
Bacteraemia † 1	1/236 (0.42%)	1	0/115 (0.00%)	0
Biliary sepsis † 1	1/236 (0.42%)	1	0/115 (0.00%)	0
Cystitis † 1	1/236 (0.42%)	1	0/115 (0.00%)	0
Liver abscess † 1	0/236 (0.00%)	0	1/115 (0.87%)	1
Lobar pneumonia † 1	0/236 (0.00%)	0	1/115 (0.87%)	1
Lung infection † 1	1/236 (0.42%)	1	1/115 (0.87%)	1
Peritonitis † 1	1/236 (0.42%)	1	0/115 (0.00%)	0
Pneumonia † 1	4/236 (1.69%)	4	2/115 (1.74%)	2
Pulmonary sepsis † 1	1/236 (0.42%)	1	0/115 (0.00%)	0
Respiratory tract infection † 1	1/236 (0.42%)	1	0/115 (0.00%)	0
Sepsis † 1	3/236 (1.27%)	3	2/115 (1.74%)	2
Septic shock † 1	0/236 (0.00%)	0	1/115 (0.87%)	1
Injury, poisoning and procedural complications
Accidental overdose † 1	2/236 (0.85%)	2	0/115 (0.00%)	0
Drug dispensing error † 1	0/236 (0.00%)	0	1/115 (0.87%)	1
Fall † 1	0/236 (0.00%)	0	2/115 (1.74%)	2
Feeding tube complication † 1	0/236 (0.00%)	0	1/115 (0.87%)	1
Incorrect dose administered † 1	0/236 (0.00%)	0	1/115 (0.87%)	1
Medication error † 1	7/236 (2.97%)	8	1/115 (0.87%)	2
Multiple injuries † 1	1/236 (0.42%)	1	0/115 (0.00%)	0
Overdose † 1	2/236 (0.85%)	2	0/115 (0.00%)	0
Underdose † 1	4/236 (1.69%)	5	1/115 (0.87%)	1
Investigations
Alanine aminotransferase increased † 1	2/236 (0.85%)	2	0/115 (0.00%)	0
Aspartate aminotransferase increased † 1	2/236 (0.85%)	2	0/115 (0.00%)	0
Blood alkaline phosphatase increased † 1	4/236 (1.69%)	4	0/115 (0.00%)	0
Blood bilirubin increased † 1	1/236 (0.42%)	1	0/115 (0.00%)	0
Weight decreased † 1	1/236 (0.42%)	1	0/115 (0.00%)	0
Metabolism and nutrition disorders
Decreased appetite † 1	4/236 (1.69%)	4	1/115 (0.87%)	1
Dehydration † 1	4/236 (1.69%)	4	3/115 (2.61%)	3
Hyperkalaemia † 1	2/236 (0.85%)	7	0/115 (0.00%)	0
Hypoalbuminaemia † 1	3/236 (1.27%)	3	0/115 (0.00%)	0
Hypocalcaemia † 1	0/236 (0.00%)	0	1/115 (0.87%)	1
Hypoglycaemia † 1	3/236 (1.27%)	3	2/115 (1.74%)	2
Hypokalaemia † 1	1/236 (0.42%)	1	1/115 (0.87%)	1
Hyponatraemia † 1	3/236 (1.27%)	3	0/115 (0.00%)	0
Hypophagia † 1	0/236 (0.00%)	0	1/115 (0.87%)	1
Hypoproteinaemia † 1	1/236 (0.42%)	1	0/115 (0.00%)	0
Musculoskeletal and connective tissue disorders
Back pain † 1	0/236 (0.00%)	0	1/115 (0.87%)	1
Flank pain † 1	1/236 (0.42%)	1	0/115 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastric cancer † 1	1/236 (0.42%)	1	0/115 (0.00%)	0
Gastric cancer recurrent † 1	1/236 (0.42%)	1	0/115 (0.00%)	0
Malignant neoplasm progression † 1	0/236 (0.00%)	0	3/115 (2.61%)	3
Malignant pleural effusion † 1	1/236 (0.42%)	1	0/115 (0.00%)	0
Metastases to central nervous system † 1	0/236 (0.00%)	0	1/115 (0.87%)	1
Metastases to spine † 1	1/236 (0.42%)	1	0/115 (0.00%)	0
Nervous system disorders
Cerebral ischaemia † 1	1/236 (0.42%)	1	0/115 (0.00%)	0
Cerebrovascular accident † 1	1/236 (0.42%)	1	0/115 (0.00%)	0
Coma † 1	1/236 (0.42%)	1	0/115 (0.00%)	0
Headache † 1	1/236 (0.42%)	1	0/115 (0.00%)	0
Hyperammonaemic encephalopathy † 1	1/236 (0.42%)	1	0/115 (0.00%)	0
Psychiatric disorders
Confusional state † 1	1/236 (0.42%)	1	0/115 (0.00%)	0
Mental status changes † 1	0/236 (0.00%)	0	1/115 (0.87%)	1
Renal and urinary disorders
Nephrolithiasis † 1	2/236 (0.85%)	2	0/115 (0.00%)	0
Renal failure acute † 1	2/236 (0.85%)	2	2/115 (1.74%)	2
Ureteric obstruction † 1	1/236 (0.42%)	1	0/115 (0.00%)	0
Ureteric perforation † 1	1/236 (0.42%)	1	0/115 (0.00%)	0
Urinary retention † 1	0/236 (0.00%)	0	1/115 (0.87%)	1
Urinary tract obstruction † 1	1/236 (0.42%)	1	0/115 (0.00%)	0
Reproductive system and breast disorders
Vaginal laceration † 1	1/67 (1.49%)	1	0/38 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnoea † 1	1/236 (0.42%)	1	2/115 (1.74%)	2
Pleural effusion † 1	1/236 (0.42%)	1	1/115 (0.87%)	1
Pulmonary embolism † 1	2/236 (0.85%)	2	2/115 (1.74%)	2
Pulmonary oedema † 1	1/236 (0.42%)	1	0/115 (0.00%)	0
Respiratory failure † 1	1/236 (0.42%)	1	2/115 (1.74%)	2
Surgical and medical procedures
Jejunostomy † 1	0/236 (0.00%)	0	1/115 (0.87%)	1
Oesophageal stent insertion † 1	1/236 (0.42%)	1	0/115 (0.00%)	0
Vascular disorders
Deep vein thrombosis † 1	0/236 (0.00%)	0	3/115 (2.61%)	3
Embolism † 1	0/236 (0.00%)	0	1/115 (0.87%)	1
Hypertension † 1	1/236 (0.42%)	1	0/115 (0.00%)	0
Hypovolaemic shock † 1	1/236 (0.42%)	1	0/115 (0.00%)	0
Orthostatic hypotension † 1	1/236 (0.42%)	1	0/115 (0.00%)	0
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 15.1
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	IMC-1121B (Ramucirumab)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	213/236 (90.25%)		91/115 (79.13%)
Blood and lymphatic system disorders
Anaemia † 1	33/236 (13.98%)	41	16/115 (13.91%)	22
Gastrointestinal disorders
Abdominal pain † 1	40/236 (16.95%)	53	26/115 (22.61%)	36
Abdominal pain upper † 1	26/236 (11.02%)	35	5/115 (4.35%)	5
Ascites † 1	18/236 (7.63%)	23	8/115 (6.96%)	8
Constipation † 1	37/236 (15.68%)	53	24/115 (20.87%)	38
Diarrhoea † 1	35/236 (14.83%)	64	9/115 (7.83%)	12
Dyspepsia † 1	6/236 (2.54%)	8	7/115 (6.09%)	7
Dysphagia † 1	23/236 (9.75%)	33	11/115 (9.57%)	22
Nausea † 1	45/236 (19.07%)	62	30/115 (26.09%)	44
Vomiting † 1	45/236 (19.07%)	70	26/115 (22.61%)	36
General disorders
Asthenia † 1	30/236 (12.71%)	60	16/115 (13.91%)	19
Fatigue † 1	58/236 (24.58%)	90	28/115 (24.35%)	52
Oedema peripheral † 1	21/236 (8.90%)	27	10/115 (8.70%)	11
Investigations
Weight decreased † 1	26/236 (11.02%)	34	11/115 (9.57%)	13
Metabolism and nutrition disorders
Decreased appetite † 1	55/236 (23.31%)	90	26/115 (22.61%)	39
Hypoalbuminaemia † 1	11/236 (4.66%)	15	6/115 (5.22%)	6
Hypokalaemia † 1	13/236 (5.51%)	20	5/115 (4.35%)	5
Musculoskeletal and connective tissue disorders
Back pain † 1	18/236 (7.63%)	22	11/115 (9.57%)	22
Pain in extremity † 1	8/236 (3.39%)	11	6/115 (5.22%)	11
Nervous system disorders
Dizziness † 1	4/236 (1.69%)	6	6/115 (5.22%)	7
Dysgeusia † 1	7/236 (2.97%)	7	6/115 (5.22%)	9
Headache † 1	21/236 (8.90%)	28	4/115 (3.48%)	4
Psychiatric disorders
Insomnia † 1	13/236 (5.51%)	14	8/115 (6.96%)	8
Respiratory, thoracic and mediastinal disorders
Cough † 1	19/236 (8.05%)	20	9/115 (7.83%)	9
Dyspnoea † 1	21/236 (8.90%)	24	15/115 (13.04%)	23
Epistaxis † 1	12/236 (5.08%)	15	1/115 (0.87%)	1
Vascular disorders
Hypertension † 1	35/236 (14.83%)	125	9/115 (7.83%)	31
Hypotension † 1	5/236 (2.12%)	6	6/115 (5.22%)	7
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 15.1

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.

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 completion 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

• 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):

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.

Fuchs CS, Tomasek J, Yong CJ, Dumitru F, Passalacqua R, Goswami C, Safran H, Dos Santos LV, Aprile G, Ferry DR, Melichar B, Tehfe M, Topuzov E, Zalcberg JR, Chau I, Campbell W, Sivanandan C, Pikiel J, Koshiji M, Hsu Y, Liepa AM, Gao L, Schwartz JD, Tabernero J; REGARD Trial Investigators. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2014 Jan 4;383(9911):31-39. doi: 10.1016/S0140-6736(13)61719-5. Epub 2013 Oct 3.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT00917384
• Other Study ID Numbers: 13893; 2008-005964-15 ( Registry Identifier: MHRA ); CP12-0715 ( Other Identifier: ImClone Systems ); I4T-IE-JVBD ( Other Identifier: Eli Lilly and Company )
• First Submitted: June 8, 2009
• First Posted: June 10, 2009
• Results First Submitted: May 21, 2014
• Results First Posted: October 16, 2014
• Last Update Posted: September 25, 2019