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

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00917384
• Collaborator: (none)
• Enrollment: 355
• Locations: 161
• Arms: 2
• Duration (Months): 76
• Patients Per Site: 2.2
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The purpose of this study is to gather information about the use of an investigational drug called Ramucirumab in adenocarcinomas of the stomach or gastroesophageal junction.

Condition or Disease	Intervention/Treatment	Phase
Gastric Cancer; Adenocarcinoma	Biological: ramucirumab; Drug: Placebo; Other: Best Supportive Care (BSC)	Phase 3

Detailed Description

Placebo-controlled, multicenter Phase 3 study of participants with metastatic gastric cancer [including adenocarcinomas of the gastroesophageal junction (GEJ)] and disease progression on standard first-line chemotherapeutic regimens. Participants will be randomized on a 2:1 basis to receive best supportive care plus ramucirumab administered every 2 weeks or best supportive care plus placebo administered every 2 weeks, respectively. Participants will undergo radiographic assessment of disease status every 6 weeks. Participant will be treated until there is evidence of progressive disease, toxicity requiring cessation, withdrawal of consent, or until other withdrawal criteria are met.

Approximately 348 participants, with histologically- or cytologically-confirmed, metastatic gastric or GEJ adenocarcinoma, and radiographically measurable disease as defined by the Response Evaluation Criteria in Solid Tumors or evaluable, nonmeasurable disease, will be randomized. Participants will be enrolled from approximately 250 study centers in North America, South America, Central America, Asia, Australia, New Zealand, and Europe.

Study Design

• Study Type: Interventional
• Actual Enrollment: 355 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Randomized, Double-Blinded Study of IMC-1121B and Best Supportive Care (BSC) Versus Placebo and BSC in the Treatment of Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma Following Disease Progression on First-Line Platinum- or Fluoropyrimidine-Containing Combination Therapy
• Study Start Date: Aug 1, 2009
• Actual Primary Completion Date: Jul 1, 2012
• Actual Study Completion Date: Dec 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ramucirumab Participants receive ramucirumab, administered via intravenous infusion every 2 weeks at a dose of 8 milligrams/kilogram (mg/kg), and best supportive care (BSC) as determined appropriate by the investigator(s). Treatment will continue until there is evidence of progressive disease (PD), the development of unacceptable toxicity, protocol noncompliance, or withdrawal of consent.	Biological: ramucirumab; Administered via intravenous infusion every 2 weeks at a dose of 8 mg/kg; Other Names: IMC-1121B LY3009806 ; Other: Best Supportive Care (BSC); BSC as determined appropriate by the investigator(s). BSC may include but are not limited to antiemetic agents, opiate and nonopiate analgesic agents, appetite stimulants, and granulocyte and erythroid growth factors.
Placebo Comparator: Placebo Participants receive injection for intravenous infusion every 2 weeks plus BSC as determined appropriate by the investigator(s). Because investigators and ancillary medical personnel will be blinded as to assignment to active therapy versus placebo, the volume of placebo to be administered will be calculated as if it were active product with a dose of 8 mg/kg. Treatment will continue until there is evidence of PD, the development of unacceptable toxicity, protocol noncompliance, or withdrawal of consent.	Drug: Placebo; Placebo comparator for ramucirumab 8 mg/kg as intravenous infusion every 2 weeks; Other: Best Supportive Care (BSC); BSC as determined appropriate by the investigator(s). BSC may include but are not limited to antiemetic agents, opiate and nonopiate analgesic agents, appetite stimulants, and granulocyte and erythroid growth factors.

Outcome Measures

Primary Outcome Measures

1. Overall Survival (OS) [Randomization up to 28 months post-randomization]

   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

Secondary Outcome Measures

1. Progression-Free Survival (PFS) [Randomization up to 17 months]

   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).

2. Percentage of Participants Who Are Progression-Free at Week 12 (PFS Rate) [Week 12 post-randomization]

   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.

3. Percentage of Participants With Objective Response (Objective Response Rate [ORR]) [Randomization up to 17 months post-randomization]

   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.

4. Duration of Response (DOR) [Randomization up to 17 months post-randomization]

   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.

5. Change From Baseline in Quality of Life (QoL) as Measured by the European Organisation for Research and Treatment of Cancer Questionnaire (EORTC-QLQ-C30) [Baseline up to Cycle 10 (18 weeks [1 cycle=2 weeks])]

   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.

6. Number of Participants With Adverse Events [Randomization up to 18 months]

   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.

7. Maximum Concentration (Cmax) of IMC-1121B [6 weeks post-randomization]

   Cmax was not analyzed as only pre-dose samples were collected.

8. Number of Participants Who Developed Antibodies Against IMC-1121B [Baseline, 12 Weeks]

   The number of participants who developed treatment emergent antibody responses to IMC-1121B after baseline.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically or cytologically confirmed gastric carcinoma, including gastric adenocarcinoma or GEJ adenocarcinoma

• Metastatic disease or locally recurrent, unresectable disease with measurable lymph node metastases

• Measurable disease and/or evaluable disease. Measurable disease is defined as at least one unidimensionally-measurable target lesion [≥ 2 centimeter (cm) with conventional techniques or ≥ 1 cm by spiral computed tomography (CT)], as defined by Response using Response Evaluation Criteria in Solid Tumors (RECIST).

Examples of evaluable, nonmeasurable disease include gastric, peritoneal, or mesenteric thickening in areas of known disease, or peritoneal nodules that are too small to be considered measurable by RECIST

• Experienced disease progression during or within 4 months after the last dose of first-line therapy for metastatic disease, or during or within 6 months after the last dose of adjuvant therapy

• Disease is not amenable to potentially curative resection

• Participant is ≥ 18 years of age

• Participant has a life expectancy of ≥ 12 weeks

• Participant resolution to Grade ≤ 1 (or to Grade ≤ 2 in the case of neuropathy) by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 3.0, of all clinically significant toxic effects of prior chemotherapy, surgery, radiotherapy, or hormonal therapy (with the exception of alopecia)

• Eastern Cooperative Oncology Group Performance Status (ECOG-PS) score of 0-1

• The participant has adequate hepatic function as defined by a total bilirubin ≤ 1.5 milligrams/deciliter (mg/dL) [25.65 micromole/liter (µmol/L)], and aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 x the upper limit of normal (ULN) [or 5.0 x the ULN in the setting of liver metastases]

• The participant has adequate renal function as defined by a serum creatinine ≤ 1.5 x the ULN, or creatinine clearance (measured via 24-hour urine collection) ≥ 40 milliliters/minute (mL/min) (that is, if serum creatinine is > 1.5 x the ULN, a 24-hour urine collection to calculate creatinine clearance must be performed)

• The participant's urinary protein is ≤ 1+ on dipstick or routine urinalysis ([UA]; if urine dipstick or routine analysis is ≥ 2+, a 24-hour urine collection for protein must demonstrate < 1000 milligrams (mg) of protein in 24 hours to allow participation in the study)

• The participant has adequate hematologic function, as evidenced by an absolute neutrophil count (ANC) ≥ 1000 microliters (µL), hemoglobin ≥ 9 grams/deciliter (g/dL) [5.58 millimoles/liter (mmol/L)], and platelets ≥ 100,000/µL

• The participant must have adequate coagulation function as defined by International Normalized Ratio (INR) ≤ 1.5 and a partial thromboplastin time (PTT) ≤ 5 seconds above the ULN (unless receiving anticoagulation therapy). Participant on anticoagulation therapy with unresected primary tumors or local tumor recurrence following resection are not eligible

• If the participant has received prior anthracycline therapy as part of his or her first-line regimen, the participant is able to engage in ordinary physical activity without significant fatigue or dyspnea

• Because the teratogenicity of IMC-1121B is not known, the participant, if sexually active, must be postmenopausal, surgically sterile, or using effective contraception (hormonal or barrier methods)

• Female participant of childbearing potential must have a negative serum pregnancy test within 7 days prior to randomization

• Able to provide informed written consent and is amenable to compliance with protocol schedules and testing

Exclusion Criteria:

• Documented and/or symptomatic brain or leptomeningeal metastases

• Experienced any Grade 3-4 gastrointestinal bleeding within 3 months prior to randomization

• Experienced any arterial thromboembolic events, including but not limited to myocardial infarction, transient ischemic attack, cerebrovascular accident, or unstable angina, within 6 months prior to randomization

• Ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, symptomatic or poorly controlled cardiac arrhythmia, uncontrolled thrombotic or hemorrhagic disorder, or any other serious uncontrolled medical disorders in the opinion of the investigator

• Ongoing or active psychiatric illness or social situation that would limit compliance with study requirements

• Uncontrolled or poorly-controlled hypertension despite standard medical management

• Participant has a serious or nonhealing wound, ulcer, or bone fracture

• Received chemotherapy, radiotherapy, immunotherapy, or targeted therapy for gastric cancer within 2 weeks prior to randomization

• Received any investigational therapy within 30 days prior to randomization

• Undergone major surgery within 28 days prior to randomization, or subcutaneous venous access device placement within 7 days prior to randomization

• Received prior therapy with an agent that directly inhibits vascular endothelial growth factor (VEGF) or VEGF receptor 2 (R-2) activity (including bevacizumab), or any antiangiogenic agent

• Receiving chronic antiplatelet therapy, including aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs, including ibuprofen, naproxen, and others), dipyridamole or clopidogrel, or similar agents. Once-daily aspirin use [maximum dose 325 milligram/day (mg/day)] is permitted

• Participant has elective or planned major surgery to be performed during the course of the clinical trial

• Participant has a known allergy to any of the treatment components

• Pregnant or lactating

• Known to be positive for infection with the human immunodeficiency virus

• Known alcohol or drug dependency

• Participant has a concurrent active malignancy other than adequately-treated nonmelanomatous skin cancer, other noninvasive carcinoma, or in situ neoplasm. A participant with previous history of malignancy is eligible, provided that he/she has been free of disease for > 3 years

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	ImClone Investigational Site	Bakersfield	California	United States	93309
2	ImClone Investigational Site	La Jolla	California	United States	92093
3	ImClone Investigational Site	Redlands	California	United States	92374
4	ImClone Investigational Site	Chicago	Illinois	United States	60612
5	ImClone Investigational Site	New Orleans	Louisiana	United States	70112
6	ImClone Investigational Site	Boston	Massachusetts	United States	02115
7	ImClone Investigational Site	Omaha	Nebraska	United States	68114
8	ImClone Investigational Site	New York	New York	United States	10003
9	ImClone Investigational Site	West Reading	Pennsylvania	United States	19611
10	ImClone Investigational Site	Providence	Rhode Island	United States	02903
11	ImClone Investigational Site	Charleston	South Carolina	United States	29425
12	ImClone Investigational Site	Knoxville	Tennessee	United States	37920
13	ImClone Investigational Site	Memphis	Tennessee	United States	38119
14	ImClone Investigational Site	Houston	Texas	United States	77030
15	ImClone Investigational Site	Buenos Aires		Argentina	1425
16	ImClone Investigational Site	Capital Federal		Argentina	1264
17	ImClone Investigational Site	Ciudad Autonoma de Buenos Aires		Argentina	C1437JCP
18	ImClone Investigational Site	Ciudada Autonoma		Argentina	C1199ABD
19	ImClone Investigational Site	Cordoba		Argentina	5000
20	ImClone Investigational Site	Rosario		Argentina	S2002KDS
21	ImClone Investigational Site	Wodonga	New South Wales	Australia	3690
22	ImClone Investigational Site	Hobart	Tasmania	Australia	7000
23	ImClone Investigational Site	East Melbourne	Victoria	Australia	3002
24	ImClone Investigational Site	Perth	Western Australia	Australia	6000
25	ImClone Investigational Site	Bedford Park		Australia	5042
26	ImClone Investigational Site	St. Leonards		Australia	NSW 2065
27	ImClone Investigational Site	Woodville		Australia	5011
28	ImClone Investigational Site	Sarajevo		Bosnia and Herzegovina	71000
29	ImClone Investigational Site	Barretos		Brazil	14784-400
30	ImClone Investigational Site	Belo Horizonte		Brazil	30110-090
31	ImClone Investigational Site	Belo Horizonte		Brazil	30150-281
32	ImClone Investigational Site	Brasilia		Brazil	70390-150
33	ImClone Investigational Site	Curitiba		Brazil	80730-130
34	ImClone Investigational Site	Curitiba		Brazil	81520-060
35	ImClone Investigational Site	Florianopolis		Brazil	88034-000
36	ImClone Investigational Site	Ijui		Brazil	98700-000
37	ImClone Investigational Site	Lajeados		Brazil	95900-000
38	ImClone Investigational Site	Londrina		Brazil	86050-190
39	ImClone Investigational Site	Passo Fundo		Brazil	99010-260
40	ImClone Investigational Site	Porto Alegre		Brazil	90035-903
41	ImClone Investigational Site	Porto Alegre		Brazil	90610-970
42	ImClone Investigational Site	Porto Alegre		Brazil	90840-440
43	ImClone Investigational Site	Sao Paulo		Brazil	01406-100
44	ImClone Investigational Site	Edmonton	Alberta	Canada	T6G 1Z2
45	ImClone Investigational Site	Montreal	Quebec	Canada	H2L 4M1
46	ImClone Investigational Site	Sherbrooke	Quebec	Canada	J1G 2E8
47	ImClone Investigational Site	Concepcion		Chile	407-0038
48	ImClone Investigational Site	La Serena		Chile
49	ImClone Investigational Site	Santiago		Chile	6570917
50	ImClone Investigational Site	Monteria		Colombia
51	ImClone Investigational Site	Osijek		Croatia	31 100
52	ImClone Investigational Site	Pula		Croatia	52100
53	ImClone Investigational Site	Slavonski Brod		Croatia	35 000
54	ImClone Investigational Site	Zagreb		Croatia	10 000
55	ImClone Investigational Site	Brno		Czechia	656 53
56	ImClone Investigational Site	Hradec Kralove		Czechia	500 05
57	ImClone Investigational Site	Liberec		Czechia	460 63
58	ImClone Investigational Site	Nova Ves pod Plesi		Czechia	262 04
59	ImClone Investigational Site	Olomouc		Czechia	775 20
60	ImClone Investigational Site	Pardubice		Czechia	532 03
61	ImClone Investigational Site	Prague		Czechia	180 81
62	ImClone Investigational Site	Praha 10		Czechia	100 34
63	ImClone Investigational Site	Praha 2		Czechia	128 08
64	ImClone Investigational Site	Pribram		Czechia	261 95
65	ImClone Investigational Site	Alexandria		Egypt	21131
66	ImClone Investigational Site	Cairo		Egypt	11796
67	ImClone Investigational Site	Guatemala		Guatemala	01010
68	ImClone Investigational Site	Guatemala		Guatemala
69	ImClone Investigational Site	Hyderabad	Andh Prad	India	500004
70	ImClone Investigational Site	Hyderabad	Andh Prad	India	500033
71	ImClone Investigational Site	New Delhi	Delhi	India	110085
72	ImClone Investigational Site	Bangalore	Karna	India	560 025
73	ImClone Investigational Site	Bangalore	Karna	India	560054
74	ImClone Investigational Site	Cochin	Kerala	India	682304
75	ImClone Investigational Site	Thiruvananthapuram	Kerala	India	695011
76	ImClone Investigational Site	Trivandrum	Kerala	India	695011
77	ImClone Investigational Site	Chennai	Kilpauk	India	600 010
78	ImClone Investigational Site	Bhopal	Madh Prad	India	462001
79	ImClone Investigational Site	Indore	Madh Prad	India	452008
80	ImClone Investigational Site	Mumbai	Mahara	India	400016
81	ImClone Investigational Site	Nashik	Mahara	India	422 004
82	ImClone Investigational Site	Pune	Mahara	India	411001
83	ImClone Investigational Site	Chennai	Tamilnadu	India	600010
84	ImClone Investigational Site	Chennai	Tamilnadu	India	600035
85	ImClone Investigational Site	Kolkata	W Bengal	India	700053
86	ImClone Investigational Site	Kolkata	W Bengal	India	700054
87	ImClone Investigational Site	Bangalore		India	560 029
88	ImClone Investigational Site	Chennai		India	600010
89	ImClone Investigational Site	Hyderabad		India	500 033
90	ImClone Investigational Site	Hyderabad		India	500004
91	ImClone Investigational Site	Kolkata		India	700053
92	ImClone Investigational Site	Mumbai		India	400 012
93	ImClone Investigational Site	Mumbai		India	400016
94	ImClone Investigational Site	Pune		India	411001
95	ImClone Investigational Site	West Bengal		India	700054
96	ImClone Investigational Site	Jakarta		Indonesia	10440
97	ImClone Investigational Site	Jakarta		Indonesia	11420
98	ImClone Investigational Site	Jakarta		Indonesia	14450
99	ImClone Investigational Site	Sumatera Utara		Indonesia	20136
100	ImClone Investigational Site	West Java		Indonesia	40161
101	ImClone Investigational Site	Aviano		Italy	33081
102	ImClone Investigational Site	Bologna		Italy	40138
103	ImClone Investigational Site	Brescia		Italy	25123
104	ImClone Investigational Site	Cremona		Italy	26100
105	ImClone Investigational Site	Lido di Camaiore		Italy	55043
106	ImClone Investigational Site	Lucca		Italy	55043
107	ImClone Investigational Site	Meldola		Italy	47014
108	ImClone Investigational Site	Mirano		Italy	30035
109	ImClone Investigational Site	Noale		Italy	30033
110	ImClone Investigational Site	Potenza		Italy	85100
111	ImClone Investigational Site	Rimini		Italy	47900
112	ImClone Investigational Site	Udine		Italy	33100
113	ImClone Investigational Site	Seoul		Korea, Republic of	120-752
114	ImClone Investigational Site	Seoul		Korea, Republic of	135-720
115	ImClone Investigational Site	Seoul		Korea, Republic of	136-705
116	ImClone Investigational Site	Seoul		Korea, Republic of	137-701
117	ImClone Investigational Site	Beirut		Lebanon
118	ImClone Investigational Site	Floriana		Malta	1941
119	ImClone Investigational Site	Floriana		Malta	FRN 1941
120	ImClone Investigational Site	Aguascelientes		Mexico	20217
121	ImClone Investigational Site	Christchurch		New Zealand	8011
122	ImClone Investigational Site	Cebu City		Philippines	6000
123	ImClone Investigational Site	Pasig City		Philippines	1604
124	ImClone Investigational Site	Gdansk		Poland	80-219
125	ImClone Investigational Site	Krakow		Poland	31-108
126	ImClone Investigational Site	Olsztyn		Poland	10-513
127	ImClone Investigational Site	Baia Mare		Romania	430031
128	ImClone Investigational Site	Cluj Napoca		Romania	400015
129	ImClone Investigational Site	Cluj Napoca		Romania	400058
130	ImClone Investigational Site	Suceava		Romania	720237
131	ImClone Investigational Site	Chelyabinsk		Russian Federation	454087
132	ImClone Investigational Site	Kursk		Russian Federation	305035
133	ImClone Investigational Site	Moscow		Russian Federation	115478
134	ImClone Investigational Site	Moscow		Russian Federation	125367
135	ImClone Investigational Site	Pyatigorsk		Russian Federation	357524
136	ImClone Investigational Site	St. Petersburg		Russian Federation	195067
137	ImClone Investigational Site	St. Petersburg		Russian Federation	197022
138	ImClone Investigational Site	St. Petersburg		Russian Federation	197758
139	ImClone Investigational Site	Cape Town		South Africa	7925
140	ImClone Investigational Site	Alcorcon		Spain	28922
141	ImClone Investigational Site	Barcelona		Spain	08035
142	ImClone Investigational Site	Barcelona		Spain	08036
143	ImClone Investigational Site	Elche		Spain	03203
144	ImClone Investigational Site	Madrid		Spain	28034
145	ImClone Investigational Site	Santander		Spain	39008
146	ImClone Investigational Site	Sevilla		Spain	41021
147	ImClone Investigational Site	Kaohsiung		Taiwan	807
148	ImClone Investigational Site	Taichung County		Taiwan	433
149	ImClone Investigational Site	Taipei		Taiwan	111
150	ImClone Investigational Site	Taipei		Taiwan	116
151	ImClone Investigational Site	Bangkok		Thailand	10400
152	ImClone Investigational Site	Chiang Mai		Thailand	50002
153	ImClone Investigational Site	Rajathevee District		Thailand	10400
154	ImClone Investigational Site	Adana		Turkey	01330
155	ImClone Investigational Site	Gaziantep		Turkey	27310
156	ImClone Investigational Site	Istanbul		Turkey	34718
157	ImClone Investigational Site	Izmir		Turkey	35100
158	ImClone Investigational Site	Bebington	Wirral	United Kingdom	L83 4JY
159	ImClone Investigational Site	London		United Kingdom	SE1 7EH
160	ImClone Investigational Site	Sutton		United Kingdom	SM2 5PT
161	ImClone Investigational Site	Wolverhampton		United Kingdom	WV10 0QP

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT00917384
• Other Study ID Numbers: 13893; 2008-005964-15; CP12-0715; I4T-IE-JVBD
• First Posted: Jun 10, 2009
• Last Update Posted: Sep 25, 2019
• Last Verified: Sep 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Eli Lilly and Company: IMC-1121B; Monoclonal antibody (MAb); Vascular endothelial growth factor (VEGF); Human vascular endothelial growth factor receptor-2 (VEGFR-2); Platinum resistant; platinum refractory; Gastric; Gastroesophageal Junction Adenocarcinoma; metastatic; Angiogenesis
• Additional relevant MeSH terms: Adenocarcinoma; Stomach Neoplasms; Ramucirumab

Study Results

Participant Flow

Pre-assignment Detail	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

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 Participants	238	117	355
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	60.0	60.0	60.0
Sex: Female, Male (Count of Participants)
Female	69 29%	38 32.5%	107 30.1%
Male	169 71%	79 67.5%	248 69.9%
Ethnicity (NIH/OMB) (Count of 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%
Region of Enrollment (participants) [Number]
Argentina	4 1.7%	2 1.7%	6 1.7%
Australia	8 3.4%	4 3.4%	12 3.4%
Bosnia and Herzegovina	1 0.4%	3 2.6%	4 1.1%
Brazil	24 10.1%	14 12%	38 10.7%
Canada	8 3.4%	2 1.7%	10 2.8%
Chile	1 0.4%	1 0.9%	2 0.6%
Colombia	2 0.8%	1 0.9%	3 0.8%
Czech Republic	24 10.1%	13 11.1%	37 10.4%
Egypt	1 0.4%	0 0%	1 0.3%
Spain	12 5%	4 3.4%	16 4.5%
United Kingdom	13 5.5%	4 3.4%	17 4.8%
Guatemala	6 2.5%	2 1.7%	8 2.3%
Croatia	7 2.9%	0 0%	7 2%
Indonesia	2 0.8%	1 0.9%	3 0.8%
India	16 6.7%	8 6.8%	24 6.8%
Italy	23 9.7%	11 9.4%	34 9.6%
Korea, Republic of	11 4.6%	6 5.1%	17 4.8%
Lebanon	1 0.4%	0 0%	1 0.3%
Malta	2 0.8%	3 2.6%	5 1.4%
New Zealand	1 0.4%	1 0.9%	2 0.6%
Philippines	1 0.4%	1 0.9%	2 0.6%
Poland	9 3.8%	4 3.4%	13 3.7%
Romania	13 5.5%	4 3.4%	17 4.8%
Russian Federation	14 5.9%	8 6.8%	22 6.2%
Thailand	1 0.4%	0 0%	1 0.3%
Turkey	5 2.1%	1 0.9%	6 1.7%
Taiwan	3 1.3%	0 0%	3 0.8%
United States	25 10.5%	18 15.4%	43 12.1%
South Africa	0 0%	1 0.9%	1 0.3%
Race (participants) [Number]
White	181 76.1%	91 77.8%	272 76.6%
Asian	39 16.4%	17 14.5%	56 15.8%
Black	4 1.7%	2 1.7%	6 1.7%
Other	14 5.9%	7 6%	21 5.9%

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.
Measure Participants	238	117
Median (95% Confidence Interval) [months]	5.2	3.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IMC-1121B (Ramucirumab), Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0473
	Comments
	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
	Parameter Dispersion	Type: Value:
	Estimation Comments

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.
Measure Participants	238	117
Median (95% Confidence Interval) [months]	2.1	1.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IMC-1121B (Ramucirumab), Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	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
	Parameter Dispersion	Type: Value:
	Estimation Comments

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.
Measure Participants	238	117
Number (95% Confidence Interval) [percentage of participants]	40.1 16.8%	15.8 13.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IMC-1121B (Ramucirumab), Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Normal Approximation
	Comments
Method of Estimation	Estimation Parameter	Difference Between Arms
	Estimated Value	24.2
	Confidence Interval	(2-Sided) 95%; 14.9 to 33.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

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.
Measure Participants	238	117
Number (95% Confidence Interval) [percentage of participants]	3.4 1.4%	2.6 2.2%

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.
Measure Participants	0	0

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.
Measure Participants	114	26
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.
Measure Participants	236	115
Participants with SAE	112 47.1%	51 43.6%
Participants with ≥ 1 treatment emergent NSAE	213 89.5%	91 77.8%

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.
Measure Participants	0	0

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.
Measure Participants	207	106
Number [participants]	6 2.5%	1 0.9%

Adverse Events

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 (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	IMC-1121B (Ramucirumab)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	112/236 (47.5%)		51/115 (44.3%)
Blood and lymphatic system disorders
Anaemia	11/236 (4.7%)	11	2/115 (1.7%)	4
Disseminated intravascular coagulation	1/236 (0.4%)	1	0/115 (0%)	0
Febrile neutropenia	1/236 (0.4%)	1	0/115 (0%)	0
Pancytopenia	0/236 (0%)	0	2/115 (1.7%)	2
Thrombocytopenia	1/236 (0.4%)	1	2/115 (1.7%)	2
Cardiac disorders
Cardiac arrest	1/236 (0.4%)	1	0/115 (0%)	0
Myocardial infarction	1/236 (0.4%)	1	0/115 (0%)	0
Sinus bradycardia	0/236 (0%)	0	1/115 (0.9%)	1
Endocrine disorders
Inappropriate antidiuretic hormone secretion	1/236 (0.4%)	1	0/115 (0%)	0
Gastrointestinal disorders
Abdominal distension	1/236 (0.4%)	1	1/115 (0.9%)	1
Abdominal pain	10/236 (4.2%)	11	3/115 (2.6%)	3
Abdominal pain upper	1/236 (0.4%)	1	0/115 (0%)	0
Ascites	6/236 (2.5%)	6	3/115 (2.6%)	4
Colonic obstruction	0/236 (0%)	0	1/115 (0.9%)	1
Constipation	0/236 (0%)	0	2/115 (1.7%)	2
Diarrhoea	0/236 (0%)	0	2/115 (1.7%)	2
Dyspepsia	0/236 (0%)	0	1/115 (0.9%)	1
Dysphagia	6/236 (2.5%)	6	3/115 (2.6%)	4
Gastric haemorrhage	1/236 (0.4%)	1	1/115 (0.9%)	1
Gastrointestinal haemorrhage	2/236 (0.8%)	2	2/115 (1.7%)	3
Gastrointestinal obstruction	0/236 (0%)	0	1/115 (0.9%)	1
Haematemesis	3/236 (1.3%)	3	0/115 (0%)	0
Ileus	1/236 (0.4%)	1	0/115 (0%)	0
Intestinal obstruction	5/236 (2.1%)	5	0/115 (0%)	0
Intestinal perforation	1/236 (0.4%)	1	0/115 (0%)	0
Large intestine perforation	1/236 (0.4%)	1	1/115 (0.9%)	1
Nausea	3/236 (1.3%)	3	0/115 (0%)	0
Obstruction gastric	2/236 (0.8%)	2	1/115 (0.9%)	1
Oesophageal fistula	0/236 (0%)	0	1/115 (0.9%)	1
Oesophageal obstruction	1/236 (0.4%)	1	0/115 (0%)	0
Oesophageal stenosis	1/236 (0.4%)	1	0/115 (0%)	0
Proctalgia	0/236 (0%)	0	1/115 (0.9%)	1
Small intestinal obstruction	2/236 (0.8%)	3	0/115 (0%)	0
Upper gastrointestinal haemorrhage	1/236 (0.4%)	1	1/115 (0.9%)	1
Vomiting	7/236 (3%)	7	5/115 (4.3%)	5
General disorders
Asthenia	0/236 (0%)	0	4/115 (3.5%)	4
Chest pain	1/236 (0.4%)	1	0/115 (0%)	0
Death	5/236 (2.1%)	5	0/115 (0%)	0
Device dislocation	0/236 (0%)	0	1/115 (0.9%)	1
Disease progression	10/236 (4.2%)	10	8/115 (7%)	8
Extravasation	1/236 (0.4%)	1	0/115 (0%)	0
Fatigue	2/236 (0.8%)	2	1/115 (0.9%)	1
General physical health deterioration	4/236 (1.7%)	4	0/115 (0%)	0
Mucosal inflammation	1/236 (0.4%)	1	0/115 (0%)	0
Multi-organ failure	6/236 (2.5%)	6	1/115 (0.9%)	1
Pain	2/236 (0.8%)	2	0/115 (0%)	0
Pyrexia	0/236 (0%)	0	1/115 (0.9%)	1
Sudden death	0/236 (0%)	0	1/115 (0.9%)	1
Systemic inflammatory response syndrome	1/236 (0.4%)	1	0/115 (0%)	0
Hepatobiliary disorders
Bile duct obstruction	1/236 (0.4%)	1	1/115 (0.9%)	1
Cholangitis	1/236 (0.4%)	1	1/115 (0.9%)	1
Cholecystitis acute	2/236 (0.8%)	2	0/115 (0%)	0
Cholestasis	1/236 (0.4%)	1	0/115 (0%)	0
Hyperbilirubinaemia	0/236 (0%)	0	1/115 (0.9%)	1
Jaundice cholestatic	1/236 (0.4%)	1	0/115 (0%)	0
Liver disorder	1/236 (0.4%)	1	0/115 (0%)	0
Infections and infestations
Abscess	0/236 (0%)	0	1/115 (0.9%)	1
Bacteraemia	1/236 (0.4%)	1	0/115 (0%)	0
Biliary sepsis	1/236 (0.4%)	1	0/115 (0%)	0
Cystitis	1/236 (0.4%)	1	0/115 (0%)	0
Liver abscess	0/236 (0%)	0	1/115 (0.9%)	1
Lobar pneumonia	0/236 (0%)	0	1/115 (0.9%)	1
Lung infection	1/236 (0.4%)	1	1/115 (0.9%)	1
Peritonitis	1/236 (0.4%)	1	0/115 (0%)	0
Pneumonia	4/236 (1.7%)	4	2/115 (1.7%)	2
Pulmonary sepsis	1/236 (0.4%)	1	0/115 (0%)	0
Respiratory tract infection	1/236 (0.4%)	1	0/115 (0%)	0
Sepsis	3/236 (1.3%)	3	2/115 (1.7%)	2
Septic shock	0/236 (0%)	0	1/115 (0.9%)	1
Injury, poisoning and procedural complications
Accidental overdose	2/236 (0.8%)	2	0/115 (0%)	0
Drug dispensing error	0/236 (0%)	0	1/115 (0.9%)	1
Fall	0/236 (0%)	0	2/115 (1.7%)	2
Feeding tube complication	0/236 (0%)	0	1/115 (0.9%)	1
Incorrect dose administered	0/236 (0%)	0	1/115 (0.9%)	1
Medication error	7/236 (3%)	8	1/115 (0.9%)	2
Multiple injuries	1/236 (0.4%)	1	0/115 (0%)	0
Overdose	2/236 (0.8%)	2	0/115 (0%)	0
Underdose	4/236 (1.7%)	5	1/115 (0.9%)	1
Investigations
Alanine aminotransferase increased	2/236 (0.8%)	2	0/115 (0%)	0
Aspartate aminotransferase increased	2/236 (0.8%)	2	0/115 (0%)	0
Blood alkaline phosphatase increased	4/236 (1.7%)	4	0/115 (0%)	0
Blood bilirubin increased	1/236 (0.4%)	1	0/115 (0%)	0
Weight decreased	1/236 (0.4%)	1	0/115 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	4/236 (1.7%)	4	1/115 (0.9%)	1
Dehydration	4/236 (1.7%)	4	3/115 (2.6%)	3
Hyperkalaemia	2/236 (0.8%)	7	0/115 (0%)	0
Hypoalbuminaemia	3/236 (1.3%)	3	0/115 (0%)	0
Hypocalcaemia	0/236 (0%)	0	1/115 (0.9%)	1
Hypoglycaemia	3/236 (1.3%)	3	2/115 (1.7%)	2
Hypokalaemia	1/236 (0.4%)	1	1/115 (0.9%)	1
Hyponatraemia	3/236 (1.3%)	3	0/115 (0%)	0
Hypophagia	0/236 (0%)	0	1/115 (0.9%)	1
Hypoproteinaemia	1/236 (0.4%)	1	0/115 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	0/236 (0%)	0	1/115 (0.9%)	1
Flank pain	1/236 (0.4%)	1	0/115 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastric cancer	1/236 (0.4%)	1	0/115 (0%)	0
Gastric cancer recurrent	1/236 (0.4%)	1	0/115 (0%)	0
Malignant neoplasm progression	0/236 (0%)	0	3/115 (2.6%)	3
Malignant pleural effusion	1/236 (0.4%)	1	0/115 (0%)	0
Metastases to central nervous system	0/236 (0%)	0	1/115 (0.9%)	1
Metastases to spine	1/236 (0.4%)	1	0/115 (0%)	0
Nervous system disorders
Cerebral ischaemia	1/236 (0.4%)	1	0/115 (0%)	0
Cerebrovascular accident	1/236 (0.4%)	1	0/115 (0%)	0
Coma	1/236 (0.4%)	1	0/115 (0%)	0
Headache	1/236 (0.4%)	1	0/115 (0%)	0
Hyperammonaemic encephalopathy	1/236 (0.4%)	1	0/115 (0%)	0
Psychiatric disorders
Confusional state	1/236 (0.4%)	1	0/115 (0%)	0
Mental status changes	0/236 (0%)	0	1/115 (0.9%)	1
Renal and urinary disorders
Nephrolithiasis	2/236 (0.8%)	2	0/115 (0%)	0
Renal failure acute	2/236 (0.8%)	2	2/115 (1.7%)	2
Ureteric obstruction	1/236 (0.4%)	1	0/115 (0%)	0
Ureteric perforation	1/236 (0.4%)	1	0/115 (0%)	0
Urinary retention	0/236 (0%)	0	1/115 (0.9%)	1
Urinary tract obstruction	1/236 (0.4%)	1	0/115 (0%)	0
Reproductive system and breast disorders
Vaginal laceration	1/67 (1.5%)	1	0/38 (0%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/236 (0.4%)	1	2/115 (1.7%)	2
Pleural effusion	1/236 (0.4%)	1	1/115 (0.9%)	1
Pulmonary embolism	2/236 (0.8%)	2	2/115 (1.7%)	2
Pulmonary oedema	1/236 (0.4%)	1	0/115 (0%)	0
Respiratory failure	1/236 (0.4%)	1	2/115 (1.7%)	2
Surgical and medical procedures
Jejunostomy	0/236 (0%)	0	1/115 (0.9%)	1
Oesophageal stent insertion	1/236 (0.4%)	1	0/115 (0%)	0
Vascular disorders
Deep vein thrombosis	0/236 (0%)	0	3/115 (2.6%)	3
Embolism	0/236 (0%)	0	1/115 (0.9%)	1
Hypertension	1/236 (0.4%)	1	0/115 (0%)	0
Hypovolaemic shock	1/236 (0.4%)	1	0/115 (0%)	0
Orthostatic hypotension	1/236 (0.4%)	1	0/115 (0%)	0
Other (Not Including Serious) Adverse Events
	IMC-1121B (Ramucirumab)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	213/236 (90.3%)		91/115 (79.1%)
Blood and lymphatic system disorders
Anaemia	33/236 (14%)	41	16/115 (13.9%)	22
Gastrointestinal disorders
Abdominal pain	40/236 (16.9%)	53	26/115 (22.6%)	36
Abdominal pain upper	26/236 (11%)	35	5/115 (4.3%)	5
Ascites	18/236 (7.6%)	23	8/115 (7%)	8
Constipation	37/236 (15.7%)	53	24/115 (20.9%)	38
Diarrhoea	35/236 (14.8%)	64	9/115 (7.8%)	12
Dyspepsia	6/236 (2.5%)	8	7/115 (6.1%)	7
Dysphagia	23/236 (9.7%)	33	11/115 (9.6%)	22
Nausea	45/236 (19.1%)	62	30/115 (26.1%)	44
Vomiting	45/236 (19.1%)	70	26/115 (22.6%)	36
General disorders
Asthenia	30/236 (12.7%)	60	16/115 (13.9%)	19
Fatigue	58/236 (24.6%)	90	28/115 (24.3%)	52
Oedema peripheral	21/236 (8.9%)	27	10/115 (8.7%)	11
Investigations
Weight decreased	26/236 (11%)	34	11/115 (9.6%)	13
Metabolism and nutrition disorders
Decreased appetite	55/236 (23.3%)	90	26/115 (22.6%)	39
Hypoalbuminaemia	11/236 (4.7%)	15	6/115 (5.2%)	6
Hypokalaemia	13/236 (5.5%)	20	5/115 (4.3%)	5
Musculoskeletal and connective tissue disorders
Back pain	18/236 (7.6%)	22	11/115 (9.6%)	22
Pain in extremity	8/236 (3.4%)	11	6/115 (5.2%)	11
Nervous system disorders
Dizziness	4/236 (1.7%)	6	6/115 (5.2%)	7
Dysgeusia	7/236 (3%)	7	6/115 (5.2%)	9
Headache	21/236 (8.9%)	28	4/115 (3.5%)	4
Psychiatric disorders
Insomnia	13/236 (5.5%)	14	8/115 (7%)	8
Respiratory, thoracic and mediastinal disorders
Cough	19/236 (8.1%)	20	9/115 (7.8%)	9
Dyspnoea	21/236 (8.9%)	24	15/115 (13%)	23
Epistaxis	12/236 (5.1%)	15	1/115 (0.9%)	1
Vascular disorders
Hypertension	35/236 (14.8%)	125	9/115 (7.8%)	31
Hypotension	5/236 (2.1%)	6	6/115 (5.2%)	7

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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.