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Trial record 1 of 3 for:    REACH ramucirumab
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A Study of Ramucirumab (IMC-1121B) Drug Product (DP) and Best Supportive Care (BSC) Versus Placebo and BSC as 2nd-Line Treatment in Participants With Hepatocellular Carcinoma After 1st-Line Therapy With Sorafenib (REACH)

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ClinicalTrials.gov Identifier: NCT01140347
Recruitment Status : Completed
First Posted : June 9, 2010
Results First Posted : March 26, 2015
Last Update Posted : December 28, 2015
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Hepatocellular Carcinoma
Interventions Biological: Placebo
Biological: Ramucirumab DP (IMC-1121B)
Other: BSC
Enrollment 565
Recruitment Details  
Pre-assignment Details Participants who died due to any cause or were alive and on study at conclusion but off treatment were considered to have completed the study.
Arm/Group Title Ramucirumab (IMC-1121B) + BSC Placebo + BSC
Hide Arm/Group Description

Ramucirumab (IMC-1121B): 8 milligrams/kilogram (mg/kg) intravenous (IV) infusion every 2 weeks.

Best supportive care (BSC): Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator.

Placebo: 8 mg/kg IV infusion every 2 weeks. BSC: Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator.
Period Title: Overall Study
Started 283 282
Received at Least 1 Dose of Study Drug 277 276
Completed 265 268
Not Completed 18 14
Reason Not Completed
Lost to Follow-up             5             6
Withdrawal by Subject             13             8
Arm/Group Title Ramucirumab (IMC-1121B) + BSC Placebo + BSC Total
Hide Arm/Group Description Ramucirumab 8 mg/kg IV infusion every 2 weeks. BSC: Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator. Placebo: 8 mg/kg IV infusion every 2 weeks. BSC: Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator. Total of all reporting groups
Overall Number of Baseline Participants 283 282 565
Hide Baseline Analysis Population Description
All randomized participants.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 283 participants 282 participants 565 participants
62.9  (11.56) 62.5  (11.10) 62.7  (11.33)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 283 participants 282 participants 565 participants
<65 years 150 162 312
≥65 years 133 120 253
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 283 participants 282 participants 565 participants
Female
47
  16.6%
40
  14.2%
87
  15.4%
Male
236
  83.4%
242
  85.8%
478
  84.6%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 283 participants 282 participants 565 participants
Hispanic or Latino
23
   8.1%
20
   7.1%
43
   7.6%
Not Hispanic or Latino
253
  89.4%
260
  92.2%
513
  90.8%
Unknown or Not Reported
7
   2.5%
2
   0.7%
9
   1.6%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 283 participants 282 participants 565 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
131
  46.3%
135
  47.9%
266
  47.1%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
5
   1.8%
3
   1.1%
8
   1.4%
White
139
  49.1%
137
  48.6%
276
  48.8%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
8
   2.8%
7
   2.5%
15
   2.7%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 283 participants 282 participants 565 participants
United States 17 20 37
Portugal 0 2 2
Philippines 1 0 1
Taiwan 33 25 58
Hong Kong 14 10 24
Spain 9 12 21
Thailand 5 1 6
Israel 1 1 2
Switzerland 1 1 2
Italy 33 18 51
France 32 27 59
Australia 3 8 11
Netherlands 2 1 3
Korea, Republic of 28 42 70
Finland 0 3 3
Austria 4 4 8
Czech Republic 11 9 20
Hungary 1 0 1
Canada 0 1 1
Belgium 3 5 8
Brazil 15 12 27
Romania 3 4 7
Bulgaria 2 4 6
Germany 19 21 40
Norway 1 1 2
Japan 45 48 93
Sweden 0 2 2
1.Primary Outcome
Title Overall Survival (OS)
Hide Description OS was defined as the time from the date of randomization to the date of death from any cause. Participants who were alive at the end of the follow-up period or were lost to follow-up were censored on the last date the participant was known to be alive.
Time Frame Randomization to death from any cause (up to 37 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) Population: All randomized participants. Participants censored: Ramucirumab+BSC (Ram)=65, Placebo+BSC (Pl)=58.
Arm/Group Title Ramucirumab (IMC-1121B) + BSC Placebo + BSC
Hide Arm/Group Description:
Ramucirumab 8 mg/kg IV infusion every 2 weeks. BSC: Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator.
Placebo: 8 mg/kg IV infusion every 2 weeks. BSC: Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator.
Overall Number of Participants Analyzed 283 282
Median (95% Confidence Interval)
Unit of Measure: months
9.17
(8.05 to 10.64)
7.62
(6.01 to 9.33)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ramucirumab (IMC-1121B) + BSC, Placebo + BSC
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1391
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.866
Confidence Interval (2-Sided) 95%
0.717 to 1.046
Estimation Comments HR with 95% confidence interval (CI) was estimated using a stratified Cox proportional hazards regression model using the Interactive Web Response System (IWRS) stratification factors (geographical regions and etiology of liver disease).
2.Secondary Outcome
Title Progression-Free Survival (PFS)
Hide Description PFS was defined as time from date of randomization until date of objectively determined progressive disease (PD) as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 or death from any cause. PD was defined as ≥20% increase in sum of diameters (SOD) of target lesions, taking as reference smallest sum on study (including baseline sum if it was smallest). Sum must show a ≥5 millimeter (mm) increase. Appearance of ≥1 new lesions and unequivocal progression of existing non-target lesions were considered progression. In primary analysis, participants alive and without PD were censored at day of last adequate tumor assessment; progression or deaths without progression occurring immediately after ≥2 missed tumor assessments, were censored at day of the last adequate tumor assessment prior to missing assessments; participants who began new anticancer therapy were censored at day of the last adequate tumor assessment prior to start of new anticancer therapy.
Time Frame Randomization to PD (up to 36 months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population: All randomized participants. Participants censored: Ram=43, Pl=19.
Arm/Group Title Ramucirumab (IMC-1121B) + BSC Placebo + BSC
Hide Arm/Group Description:
Ramucirumab 8 mg/kg IV infusion every 2 weeks. BSC: Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator.
Placebo: 8 mg/kg IV infusion every 2 weeks. BSC: Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator.
Overall Number of Participants Analyzed 283 282
Median (95% Confidence Interval)
Unit of Measure: months
2.79
(2.69 to 3.94)
2.10
(1.58 to 2.69)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ramucirumab (IMC-1121B) + BSC, Placebo + BSC
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.625
Confidence Interval (2-Sided) 95%
0.522 to 0.750
Estimation Comments HR with 95% CI was estimated using a stratified Cox proportional hazards regression model using the IWRS stratification factors (geographical regions and etiology of liver disease).
3.Secondary Outcome
Title Percentage of Participants With Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)]
Hide Description ORR was defined, using RECIST v1.1 criteria, as the percentage of participants who achieved a best overall response of CR or PR. CR was defined as the disappearance of all lesions and any intratumor arterial enhancement in target lesions, the normalization of the tumor marker level and all lymph nodes short axis reduced to <10 mm. PR was defined as ≥30% decrease in the SOD of target lesions, including the short axes of any target lymph nodes, taking as reference the baseline SOD of target lesions, no new lesions and stable nontarget lesions. Percentage of participants was calculated as: (number of participants with CR or PR / number of participants randomized) * 100.
Time Frame Baseline to the date of first evidence of confirmed CR or PR (up to 37 months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population: All randomized participants.
Arm/Group Title Ramucirumab (IMC-1121B) + BSC Placebo + BSC
Hide Arm/Group Description:
Ramucirumab 8 mg/kg IV infusion every 2 weeks. BSC: Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator.
Placebo: 8 mg/kg IV infusion every 2 weeks. BSC: Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator.
Overall Number of Participants Analyzed 283 282
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
7.1
(4.6 to 10.7)
0.7
(0.2 to 2.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ramucirumab (IMC-1121B) + BSC, Placebo + BSC
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel (CMH) adjusted for geographic region and etiology liver disease
4.Secondary Outcome
Title Time to Radiographic Progression (TTP)
Hide Description TTP was defined as the time from randomization to the first radiographically documented PD. PD was defined, using RECIST v1.1 criteria, as ≥20% increase in SOD of target lesions, taking as reference smallest sum on study (including baseline sum if it was the smallest). Sum must show an absolute increase of ≥5 mm. Appearance of ≥1 new lesions and unequivocal progression of existing non-target lesions were considered progression. Participants without PD were censored at the day of the last adequate tumor assessment. Progression occurred immediately after ≥2 missed tumor assessments and were censored at the day of the last adequate tumor assessment prior to the missing assessments. Participants who began new anticancer therapy were censored at the day of their last adequate tumor assessment prior to start of new anticancer therapy.
Time Frame Randomization to PD (up to 36 months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population: All randomized participants. Participants censored: Ram=86, Pl=52.
Arm/Group Title Ramucirumab (IMC-1121B) + BSC Placebo + BSC
Hide Arm/Group Description:
Ramucirumab 8 mg/kg IV infusion every 2 weeks. BSC: Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator.
Placebo: 8 mg/kg IV infusion every 2 weeks. BSC: Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator.
Overall Number of Participants Analyzed 283 282
Median (95% Confidence Interval)
Unit of Measure: months
3.48
(2.76 to 4.47)
2.63
(1.58 to 2.76)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ramucirumab (IMC-1121B) + BSC, Placebo + BSC
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.593
Confidence Interval (2-Sided) 95%
0.487 to 0.722
Estimation Comments HR with 95% CI was estimated using a stratified Cox proportional hazards regression model using the IWRS stratification factors (geographical regions and etiology of liver disease).
5.Secondary Outcome
Title Change From Baseline in the Functional Assessment of Cancer Therapy (FACT) Hepatobiliary Symptom Index-8 (FHSI-8)
Hide Description The FHSI-8 is a self-administered 8-item questionnaire that measures a participant's symptoms in the domains of jaundice, stomach pain/discomfort weight loss, and fatigue. Participants rated each item on a 5-point scale from 0 (not at all) to 4 (very much). Item scores were calculated as outlined in the FACIT manual. FHSI-8 total score was the sum of each item's score with a total score ranging from 0 (highly symptomatic) to 32 (asymptomatic).
Time Frame Baseline, Prior to infusion on Day 1 of Cycle 4, Cycle 10, and Cycle 16 (14-day cycles), and end of treatment (up to 34 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who had FHSI-8 at baseline and the specified time points.
Arm/Group Title Ramucirumab (IMC-1121B) + BSC Placebo + BSC
Hide Arm/Group Description:
Ramucirumab 8 mg/kg IV infusion every 2 weeks. BSC: Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator.
Placebo: 8 mg/kg IV infusion every 2 weeks. BSC: Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator.
Overall Number of Participants Analyzed 169 199
Mean (Standard Deviation)
Unit of Measure: units on a scale
Cycle 4 (n=166, 147) -1.26  (3.164) -0.81  (4.623)
Cycle 10 (n=70, 45) -1.28  (3.989) -0.01  (4.378)
Cycle 16 (n=47, 24) -0.97  (4.095) 0.75  (3.768)
End of Treatment (n=169, 199) -2.44  (5.561) -2.86  (5.618)
6.Secondary Outcome
Title Change From Baseline in European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score
Hide Description The EQ-5D is a self-reported, 5-dimension (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) questionnaire related to the participant's current health state. Each question was scored using a 3 level scale (no problems, some problems, or extreme problems). EQ-5D health state was defined by combining responses from each of the 5 dimensions into a weighted health-state index score according to the United Kingdom (UK) population based algorithm where 0 = death and 1 = perfect health.
Time Frame Baseline, Prior to infusion on Day 1 of Cycle 4, Cycle 10, and Cycle 16 (14-day cycles), end of treatment (up to 34 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who had an EQ-5D score at baseline and the specified time points.
Arm/Group Title Ramucirumab (IMC-1121B) + BSC Placebo + BSC
Hide Arm/Group Description:
Ramucirumab 8 mg/kg IV infusion every 2 weeks. BSC: Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator.
Placebo: 8 mg/kg IV infusion every 2 weeks. BSC: Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator.
Overall Number of Participants Analyzed 166 190
Mean (Standard Deviation)
Unit of Measure: units on a scale
Cycle 4 (n=166, 145) -0.038  (0.189) -0.046  (0.245)
Cycle 10 (n=71, 45) -0.054  (0.212) 0.003  (0.148)
Cycle 16 (n=47, 25) -0.062  (0.214) -0.012  (0.085)
End of Treatment (n=166, 190) -0.129  (0.290) -0.144  (0.280)
7.Secondary Outcome
Title Number of Participants With Adverse Events (AEs) and the Number of Participants Who Died
Hide Description The number of participants with serious AEs (SAEs), other non-serious AEs and participants who died. A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.
Time Frame Baseline to study completion (up to 37 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study drug.
Arm/Group Title Ramucirumab (IMC-1121B) + BSC Placebo + BSC
Hide Arm/Group Description:
Ramucirumab 8 mg/kg IV infusion every 2 weeks. BSC: Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator.
Placebo: 8 mg/kg IV infusion every 2 weeks. BSC: Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator.
Overall Number of Participants Analyzed 277 276
Measure Type: Number
Unit of Measure: participants
SAEs 123 92
Other Non-SAEs 254 235
Died 215 220
8.Secondary Outcome
Title Maximum Concentration (Cmax) of Ramucirumab, Cycle 1
Hide Description [Not Specified]
Time Frame 1 hour following the completion of Cycle 1 (14-day cycle) infusion
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received Cycle 1 of Ram and had Cmax results.
Arm/Group Title Ramucirumab (IMC-1121B) + BSC
Hide Arm/Group Description:
Ramucirumab 8 mg/kg IV infusion every 2 weeks. BSC: Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator.
Overall Number of Participants Analyzed 247
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: micrograms/milliliter (µg/mL)
149.6
(36.9%)
9.Secondary Outcome
Title Cmax of Ramucirumab, Cycle 4
Hide Description [Not Specified]
Time Frame 1 hour following completion of Cycle 4 (14-day cycles) infusion
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received Cycle 4 of Ram and had Cmax results.
Arm/Group Title Ramucirumab (IMC-1121B) + BSC
Hide Arm/Group Description:
Ramucirumab 8 mg/kg IV infusion every 2 weeks. BSC: Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator.
Overall Number of Participants Analyzed 140
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: µg/mL
189.5
(39.1%)
10.Secondary Outcome
Title Cmax of Ramucirumab, Cycle 7
Hide Description [Not Specified]
Time Frame 1 hour following completion of Cycle 7 (14-day cycles) infusion
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received Cycle 7 of Ram and had Cmax results.
Arm/Group Title Ramucirumab (IMC-1121B) + BSC
Hide Arm/Group Description:
Ramucirumab 8 mg/kg IV infusion every 2 weeks. BSC: Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator.
Overall Number of Participants Analyzed 81
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: µg/mL
184.4
(56.3%)
11.Secondary Outcome
Title Number of Participants With Treatment Emergent Positive Anti-Ramucirumab Response [Serum Anti-Ramucirumab Antibody Assessment (Immunogenicity)]
Hide Description Participants were considered positive for anti-ramucirumab antibodies [anti-drug antibodies (ADA)] if the post-treatment sample had an increase of at least 4-fold in titer from the pretreatment values. If the pretreatment value was not detected or was not present, a 1:20 post-treatment titer was required to indicate treatment emergence of ADA.
Time Frame Prior to treatment and 1 hour post end of infusion for Cycles 1, 4 and 7 (14-day cycles)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study drug and had post-treatment ADA analysis.
Arm/Group Title Ramucirumab (IMC-1121B) + BSC Placebo + BSC
Hide Arm/Group Description:
Ramucirumab 8 mg/kg IV infusion every 2 weeks. BSC: Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator.
Placebo: 8 mg/kg IV infusion every 2 weeks. BSC: Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator.
Overall Number of Participants Analyzed 241 231
Measure Type: Number
Unit of Measure: participants
10 7
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Ramucirumab (IMC-1121B) + BSC Placebo + BSC
Hide Arm/Group Description Ramucirumab 8 mg/kg IV infusion every 2 weeks. BSC: Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator. Placebo: 8 mg/kg IV infusion every 2 weeks. BSC: Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator.
All-Cause Mortality
Ramucirumab (IMC-1121B) + BSC Placebo + BSC
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Hide Serious Adverse Events
Ramucirumab (IMC-1121B) + BSC Placebo + BSC
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   124/277 (44.77%)      92/276 (33.33%)    
Blood and lymphatic system disorders     
Anaemia  1  0/277 (0.00%)  0 2/276 (0.72%)  2
Disseminated intravascular coagulation  1  1/277 (0.36%)  1 0/276 (0.00%)  0
Neutropenia  1  1/277 (0.36%)  1 0/276 (0.00%)  0
Thrombocytopenia  1  1/277 (0.36%)  1 0/276 (0.00%)  0
Cardiac disorders     
Cardiac failure  1  0/277 (0.00%)  0 1/276 (0.36%)  1
Pericardial effusion  1  1/277 (0.36%)  1 0/276 (0.00%)  0
Supraventricular tachycardia  1  1/277 (0.36%)  1 0/276 (0.00%)  0
Eye disorders     
Retinal detachment  1  1/277 (0.36%)  1 0/276 (0.00%)  0
Gastrointestinal disorders     
Abdominal distension  1  1/277 (0.36%)  2 1/276 (0.36%)  1
Abdominal pain  1  6/277 (2.17%)  7 9/276 (3.26%)  10
Abdominal pain upper  1  0/277 (0.00%)  0 1/276 (0.36%)  1
Ascites  1  8/277 (2.89%)  8 3/276 (1.09%)  4
Colitis  1  0/277 (0.00%)  0 1/276 (0.36%)  1
Diarrhoea  1  1/277 (0.36%)  2 0/276 (0.00%)  0
Duodenal ulcer  1  1/277 (0.36%)  1 0/276 (0.00%)  0
Dysphagia  1  1/277 (0.36%)  1 0/276 (0.00%)  0
Food poisoning  1  1/277 (0.36%)  1 0/276 (0.00%)  0
Gastric antral vascular ectasia  1  1/277 (0.36%)  1 0/276 (0.00%)  0
Gastric haemorrhage  1  1/277 (0.36%)  1 1/276 (0.36%)  1
Gastric varices haemorrhage  1  1/277 (0.36%)  1 0/276 (0.00%)  0
Gastroduodenitis  1  1/277 (0.36%)  1 0/276 (0.00%)  0
Gastrointestinal haemorrhage  1  7/277 (2.53%)  7 0/276 (0.00%)  0
Haemorrhoids  1  0/277 (0.00%)  0 1/276 (0.36%)  2
Ileus  1  0/277 (0.00%)  0 1/276 (0.36%)  1
Inguinal hernia  1  0/277 (0.00%)  0 1/276 (0.36%)  1
Intestinal obstruction  1  0/277 (0.00%)  0 1/276 (0.36%)  1
Irritable bowel syndrome  1  1/277 (0.36%)  1 0/276 (0.00%)  0
Large intestine perforation  1  1/277 (0.36%)  1 0/276 (0.00%)  0
Melaena  1  0/277 (0.00%)  0 1/276 (0.36%)  1
Nausea  1  2/277 (0.72%)  2 1/276 (0.36%)  1
Oesophageal haemorrhage  1  1/277 (0.36%)  1 1/276 (0.36%)  2
Oesophageal varices haemorrhage  1  4/277 (1.44%)  5 10/276 (3.62%)  12
Pancreatitis  1  0/277 (0.00%)  0 1/276 (0.36%)  1
Peritoneal haemorrhage  1  1/277 (0.36%)  1 0/276 (0.00%)  0
Small intestinal obstruction  1  0/277 (0.00%)  0 1/276 (0.36%)  1
Umbilical hernia  1  1/277 (0.36%)  1 0/276 (0.00%)  0
Upper gastrointestinal haemorrhage  1  2/277 (0.72%)  2 1/276 (0.36%)  1
Varices oesophageal  1  1/277 (0.36%)  2 0/276 (0.00%)  0
Vomiting  1  1/277 (0.36%)  2 1/276 (0.36%)  1
General disorders     
Asthenia  1  4/277 (1.44%)  5 1/276 (0.36%)  1
Chills  1  1/277 (0.36%)  1 0/276 (0.00%)  0
Death  1  1/277 (0.36%)  1 0/276 (0.00%)  0
Extravasation  1  0/277 (0.00%)  0 1/276 (0.36%)  1
Fatigue  1  1/277 (0.36%)  1 2/276 (0.72%)  2
General physical health deterioration  1  9/277 (3.25%)  9 3/276 (1.09%)  4
Generalised oedema  1  1/277 (0.36%)  1 0/276 (0.00%)  0
Hernia obstructive  1  1/277 (0.36%)  1 0/276 (0.00%)  0
Hyperthermia  1  1/277 (0.36%)  1 0/276 (0.00%)  0
Malaise  1  0/277 (0.00%)  0 1/276 (0.36%)  1
Multi-organ failure  1  2/277 (0.72%)  2 1/276 (0.36%)  2
Non-cardiac chest pain  1  1/277 (0.36%)  1 1/276 (0.36%)  1
Oedema  1  0/277 (0.00%)  0 2/276 (0.72%)  2
Oedema peripheral  1  2/277 (0.72%)  2 1/276 (0.36%)  1
Pyrexia  1  7/277 (2.53%)  8 3/276 (1.09%)  3
Sudden death  1  1/277 (0.36%)  1 0/276 (0.00%)  0
Hepatobiliary disorders     
Acute hepatic failure  1  1/277 (0.36%)  1 0/276 (0.00%)  0
Bile duct stone  1  1/277 (0.36%)  2 1/276 (0.36%)  1
Cholangitis  1  5/277 (1.81%)  8 1/276 (0.36%)  1
Cholangitis acute  1  1/277 (0.36%)  1 1/276 (0.36%)  1
Hepatic cirrhosis  1  1/277 (0.36%)  1 1/276 (0.36%)  1
Hepatic failure  1  6/277 (2.17%)  9 5/276 (1.81%)  9
Hepatic function abnormal  1  0/277 (0.00%)  0 1/276 (0.36%)  1
Hepatorenal syndrome  1  4/277 (1.44%)  4 1/276 (0.36%)  1
Hyperbilirubinaemia  1  1/277 (0.36%)  1 3/276 (1.09%)  3
Hypertransaminasaemia  1  1/277 (0.36%)  1 0/276 (0.00%)  0
Jaundice  1  1/277 (0.36%)  1 1/276 (0.36%)  1
Jaundice cholestatic  1  0/277 (0.00%)  0 2/276 (0.72%)  2
Liver disorder  1  1/277 (0.36%)  1 0/276 (0.00%)  0
Portal vein thrombosis  1  1/277 (0.36%)  1 1/276 (0.36%)  1
Immune system disorders     
Anaphylactic reaction  1  2/277 (0.72%)  2 0/276 (0.00%)  0
Infections and infestations     
Anal abscess  1  2/277 (0.72%)  2 0/276 (0.00%)  0
Bacteraemia  1  1/277 (0.36%)  2 0/276 (0.00%)  0
Campylobacter infection  1  1/277 (0.36%)  1 0/276 (0.00%)  0
Candida sepsis  1  1/277 (0.36%)  1 0/276 (0.00%)  0
Device related infection  1  1/277 (0.36%)  1 0/276 (0.00%)  0
Device related sepsis  1  1/277 (0.36%)  1 0/276 (0.00%)  0
Infection  1  1/277 (0.36%)  1 0/276 (0.00%)  0
Influenza  1  0/277 (0.00%)  0 1/276 (0.36%)  1
Liver abscess  1  1/277 (0.36%)  1 0/276 (0.00%)  0
Lobar pneumonia  1  1/277 (0.36%)  1 0/276 (0.00%)  0
Lung infection  1  2/277 (0.72%)  2 0/276 (0.00%)  0
Peritonitis  1  1/277 (0.36%)  1 1/276 (0.36%)  1
Peritonitis bacterial  1  1/277 (0.36%)  1 0/276 (0.00%)  0
Pneumonia  1  3/277 (1.08%)  3 3/276 (1.09%)  4
Pneumonia bacterial  1  1/277 (0.36%)  1 0/276 (0.00%)  0
Pneumonia klebsiella  1  0/277 (0.00%)  0 1/276 (0.36%)  1
Pulmonary sepsis  1  1/277 (0.36%)  1 0/276 (0.00%)  0
Sepsis  1  3/277 (1.08%)  3 2/276 (0.72%)  3
Septic shock  1  0/277 (0.00%)  0 1/276 (0.36%)  2
Upper respiratory tract infection  1  1/277 (0.36%)  1 1/276 (0.36%)  1
Urinary tract infection  1  3/277 (1.08%)  4 0/276 (0.00%)  0
Injury, poisoning and procedural complications     
Fall  1  0/277 (0.00%)  0 1/276 (0.36%)  1
Femur fracture  1  0/277 (0.00%)  0 1/276 (0.36%)  1
Infusion related reaction  1  1/277 (0.36%)  1 0/276 (0.00%)  0
Investigations     
Aspartate aminotransferase increased  1  0/277 (0.00%)  0 1/276 (0.36%)  1
Blood bilirubin increased  1  2/277 (0.72%)  2 0/276 (0.00%)  0
Blood creatinine increased  1  1/277 (0.36%)  1 0/276 (0.00%)  0
General physical condition abnormal  1  1/277 (0.36%)  1 0/276 (0.00%)  0
Liver function test abnormal  1  1/277 (0.36%)  1 0/276 (0.00%)  0
Metabolism and nutrition disorders     
Cachexia  1  1/277 (0.36%)  2 1/276 (0.36%)  1
Decreased appetite  1  3/277 (1.08%)  3 0/276 (0.00%)  0
Dehydration  1  2/277 (0.72%)  2 1/276 (0.36%)  1
Diabetes mellitus  1  1/277 (0.36%)  1 0/276 (0.00%)  0
Hypercalcaemia  1  1/277 (0.36%)  1 1/276 (0.36%)  1
Hyperglycaemia  1  0/277 (0.00%)  0 2/276 (0.72%)  2
Hyperkalaemia  1  1/277 (0.36%)  1 0/276 (0.00%)  0
Hypertriglyceridaemia  1  1/277 (0.36%)  1 0/276 (0.00%)  0
Hypocalcaemia  1  1/277 (0.36%)  1 0/276 (0.00%)  0
Hypoglycaemia  1  0/277 (0.00%)  0 1/276 (0.36%)  1
Hyponatraemia  1  1/277 (0.36%)  1 1/276 (0.36%)  1
Musculoskeletal and connective tissue disorders     
Arthritis  1  1/277 (0.36%)  1 0/276 (0.00%)  0
Back pain  1  0/277 (0.00%)  0 4/276 (1.45%)  4
Flank pain  1  0/277 (0.00%)  0 1/276 (0.36%)  1
Musculoskeletal chest pain  1  0/277 (0.00%)  0 1/276 (0.36%)  1
Neck pain  1  1/277 (0.36%)  1 0/276 (0.00%)  0
Pathological fracture  1  1/277 (0.36%)  2 0/276 (0.00%)  0
Spinal pain  1  0/277 (0.00%)  0 1/276 (0.36%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Liver carcinoma ruptured  1  2/277 (0.72%)  3 2/276 (0.72%)  2
Malignant neoplasm progression  1  23/277 (8.30%)  30 16/276 (5.80%)  22
Metastases to bone  1  1/277 (0.36%)  1 1/276 (0.36%)  1
Metastases to central nervous system  1  1/277 (0.36%)  1 0/276 (0.00%)  0
Metastases to lung  1  1/277 (0.36%)  2 0/276 (0.00%)  0
Small intestine adenocarcinoma  1  0/277 (0.00%)  0 1/276 (0.36%)  1
Tumour associated fever  1  1/277 (0.36%)  1 0/276 (0.00%)  0
Tumour pain  1  0/277 (0.00%)  0 4/276 (1.45%)  5
Nervous system disorders     
Central nervous system lesion  1  1/277 (0.36%)  1 0/276 (0.00%)  0
Cerebral infarction  1  0/277 (0.00%)  0 1/276 (0.36%)  1
Coma hepatic  1  1/277 (0.36%)  1 0/276 (0.00%)  0
Convulsion  1  2/277 (0.72%)  2 0/276 (0.00%)  0
Diplegia  1  1/277 (0.36%)  1 0/276 (0.00%)  0
Dizziness  1  1/277 (0.36%)  1 1/276 (0.36%)  1
Encephalopathy  1  1/277 (0.36%)  1 0/276 (0.00%)  0
Hepatic encephalopathy  1  12/277 (4.33%)  16 1/276 (0.36%)  1
Mental impairment  1  1/277 (0.36%)  2 0/276 (0.00%)  0
Peripheral motor neuropathy  1  0/277 (0.00%)  0 1/276 (0.36%)  1
Somnolence  1  1/277 (0.36%)  1 0/276 (0.00%)  0
Spinal cord compression  1  1/277 (0.36%)  1 0/276 (0.00%)  0
Subarachnoid haemorrhage  1  0/277 (0.00%)  0 1/276 (0.36%)  1
Tongue biting  1  0/277 (0.00%)  0 1/276 (0.36%)  1
Psychiatric disorders     
Mental status changes  1  0/277 (0.00%)  0 1/276 (0.36%)  1
Renal and urinary disorders     
Renal failure  1  2/277 (0.72%)  4 0/276 (0.00%)  0
Renal failure acute  1  3/277 (1.08%)  4 1/276 (0.36%)  1
Renal impairment  1  1/277 (0.36%)  1 0/276 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Acute respiratory distress syndrome  1  0/277 (0.00%)  0 1/276 (0.36%)  2
Dyspnoea  1  1/277 (0.36%)  1 2/276 (0.72%)  3
Haemoptysis  1  2/277 (0.72%)  2 1/276 (0.36%)  1
Hypoxia  1  1/277 (0.36%)  1 0/276 (0.00%)  0
Pleural effusion  1  2/277 (0.72%)  2 3/276 (1.09%)  5
Pneumonitis  1  0/277 (0.00%)  0 1/276 (0.36%)  1
Pulmonary embolism  1  1/277 (0.36%)  1 2/276 (0.72%)  3
Pulmonary haemorrhage  1  0/277 (0.00%)  0 1/276 (0.36%)  1
Skin and subcutaneous tissue disorders     
Dermatitis allergic  1  1/277 (0.36%)  1 0/276 (0.00%)  0
Skin lesion  1  1/277 (0.36%)  1 0/276 (0.00%)  0
Skin ulcer  1  1/277 (0.36%)  1 0/276 (0.00%)  0
Vascular disorders     
Deep vein thrombosis  1  2/277 (0.72%)  2 0/276 (0.00%)  0
Haemorrhage  1  0/277 (0.00%)  0 1/276 (0.36%)  1
Hypertension  1  1/277 (0.36%)  2 0/276 (0.00%)  0
Shock haemorrhagic  1  1/277 (0.36%)  1 0/276 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.1
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Ramucirumab (IMC-1121B) + BSC Placebo + BSC
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   254/277 (91.70%)      235/276 (85.14%)    
Blood and lymphatic system disorders     
Anaemia  1  29/277 (10.47%)  54 31/276 (11.23%)  44
Leukopenia  1  14/277 (5.05%)  54 7/276 (2.54%)  19
Neutropenia  1  16/277 (5.78%)  80 4/276 (1.45%)  8
Thrombocytopenia  1  48/277 (17.33%)  189 12/276 (4.35%)  26
Gastrointestinal disorders     
Abdominal distension  1  19/277 (6.86%)  27 28/276 (10.14%)  31
Abdominal pain  1  45/277 (16.25%)  63 58/276 (21.01%)  86
Abdominal pain upper  1  26/277 (9.39%)  34 25/276 (9.06%)  32
Ascites  1  72/277 (25.99%)  110 40/276 (14.49%)  47
Constipation  1  36/277 (13.00%)  39 34/276 (12.32%)  39
Diarrhoea  1  50/277 (18.05%)  74 38/276 (13.77%)  52
Gingival bleeding  1  18/277 (6.50%)  22 4/276 (1.45%)  4
Nausea  1  52/277 (18.77%)  71 52/276 (18.84%)  74
Vomiting  1  30/277 (10.83%)  39 40/276 (14.49%)  47
General disorders     
Asthenia  1  50/277 (18.05%)  80 36/276 (13.04%)  63
Fatigue  1  66/277 (23.83%)  97 60/276 (21.74%)  99
Oedema peripheral  1  100/277 (36.10%)  151 50/276 (18.12%)  58
Pyrexia  1  42/277 (15.16%)  59 25/276 (9.06%)  32
Hepatobiliary disorders     
Hyperbilirubinaemia  1  10/277 (3.61%)  16 15/276 (5.43%)  32
Infections and infestations     
Nasopharyngitis  1  15/277 (5.42%)  15 14/276 (5.07%)  16
Investigations     
Alanine aminotransferase increased  1  13/277 (4.69%)  34 21/276 (7.61%)  33
Aspartate aminotransferase increased  1  30/277 (10.83%)  59 39/276 (14.13%)  70
Blood alkaline phosphatase increased  1  18/277 (6.50%)  40 14/276 (5.07%)  25
Blood bilirubin increased  1  19/277 (6.86%)  39 24/276 (8.70%)  38
Metabolism and nutrition disorders     
Decreased appetite  1  59/277 (21.30%)  81 50/276 (18.12%)  62
Hypoalbuminaemia  1  33/277 (11.91%)  66 14/276 (5.07%)  27
Hyponatraemia  1  13/277 (4.69%)  21 15/276 (5.43%)  20
Musculoskeletal and connective tissue disorders     
Arthralgia  1  19/277 (6.86%)  26 10/276 (3.62%)  12
Back pain  1  23/277 (8.30%)  27 23/276 (8.33%)  32
Musculoskeletal pain  1  18/277 (6.50%)  26 12/276 (4.35%)  13
Nervous system disorders     
Dizziness  1  23/277 (8.30%)  25 16/276 (5.80%)  18
Headache  1  53/277 (19.13%)  69 15/276 (5.43%)  18
Psychiatric disorders     
Insomnia  1  19/277 (6.86%)  20 20/276 (7.25%)  20
Renal and urinary disorders     
Proteinuria  1  46/277 (16.61%)  117 13/276 (4.71%)  18
Respiratory, thoracic and mediastinal disorders     
Cough  1  41/277 (14.80%)  54 25/276 (9.06%)  29
Dyspnoea  1  26/277 (9.39%)  33 26/276 (9.42%)  33
Epistaxis  1  38/277 (13.72%)  48 17/276 (6.16%)  22
Skin and subcutaneous tissue disorders     
Dry skin  1  16/277 (5.78%)  17 12/276 (4.35%)  13
Pruritus  1  28/277 (10.11%)  33 29/276 (10.51%)  41
Rash  1  23/277 (8.30%)  27 12/276 (4.35%)  16
Vascular disorders     
Hypertension  1  55/277 (19.86%)  104 20/276 (7.25%)  43
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Investigators agreed to delay independently publishing or disclosing data, findings or conclusions from the study except as part of a multi-center publication. Upon study publication or if the draft publication is not produced within approximately 6 months of the final report of the study results, investigators may independently publish, subject to confidential information review/redaction by sponsor. The sponsor may request publication delay up to 90 days to seek patent protection.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
Phone: 800-545-5979
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01140347    
Other Study ID Numbers: 13895
CP12-0919 ( Other Identifier: ImClone Systems )
I4T-IE-JVBF ( Other Identifier: Eli Lilly and Company )
2010-019318-26 ( EudraCT Number )
First Submitted: June 2, 2010
First Posted: June 9, 2010
Results First Submitted: March 13, 2015
Results First Posted: March 26, 2015
Last Update Posted: December 28, 2015