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A Study of Ramucirumab (LY3009806) Versus Placebo in Participants With Hepatocellular Carcinoma and Elevated Baseline Alpha-Fetoprotein (REACH-2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02435433
Recruitment Status : Recruiting
First Posted : May 6, 2015
Results First Posted : May 17, 2019
Last Update Posted : December 16, 2019
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 Drug: Ramucirumab
Drug: Placebo
Enrollment 292
Recruitment Details  
Pre-assignment Details Completers include participants who had died due to any cause or alive and on study at the end of study, but off treatment. Results for open label and maximum extended enrollment participants will be posted after the study completion.
Arm/Group Title Ramucirumab Placebo Open Label Ramucirumab Ramucirumab ME2 Cohort Placebo ME2 Cohort
Hide Arm/Group Description 8 milligrams per kilogram (mg/kg) ramucirumab administered as an intravenous (IV) injection on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.

Placebo administered IV on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.

Participants still on treatment at the time of study completion may have the option to crossover to the ramucirumab arm.

8 mg/kg ramucirumab administered IV on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met. 8 mg/kg ramucirumab administered IV on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.

Placebo administered IV on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.

Participants still on treatment at the time of study completion may have the option to crossover to the ramucirumab arm.

Period Title: Overall Study
Started 197 95 0 0 0
Participants Who Received Study Drug 197 95 0 0 0
Completed 182 90 0 0 0
Not Completed 15 5 0 0 0
Reason Not Completed
On Treatment             11             0             0             0             0
Withdrawal by Subject             2             3             0             0             0
Lost to Follow-up             2             2             0             0             0
Arm/Group Title Ramucirumab + BSC Placebo + Best Supportive Care (BSC) Total
Hide Arm/Group Description 8 mg/kg ramucirumab administered as an IV injection on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.

Placebo administered IV on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.

Participants still on treatment at the time of study completion may have the option to crossover to the ramucirumab arm.

Total of all reporting groups
Overall Number of Baseline Participants 197 95 292
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 197 participants 95 participants 292 participants
64
(30 to 88)
64
(26 to 85)
64
(26 to 88)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 197 participants 95 participants 292 participants
Female 43 16 59
Male 154 79 233
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 197 participants 95 participants 292 participants
Hispanic or Latino 12 9 21
Not Hispanic or Latino 129 58 187
Unknown or Not Reported 56 28 84
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 197 participants 95 participants 292 participants
American Indian or Alaska Native 0 0 0
Asian 102 45 147
Native Hawaiian or Other Pacific Islander 0 0 0
Black or African American 1 1 2
White 60 31 91
More than one race 0 1 1
Unknown or Not Reported 34 17 51
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 197 participants 95 participants 292 participants
Hong Kong 6 1 7
United States 10 1 11
Czechia 4 2 6
Japan 41 18 59
United Kingdom 9 2 11
Switzerland 2 2 4
Spain 3 2 5
Canada 1 1 2
Austria 1 1 2
South Korea 24 14 38
Belgium 2 2 4
China 3 1 4
Taiwan 22 11 33
Brazil 5 4 9
Poland 2 3 5
Italy 13 9 22
Israel 1 0 1
Australia 2 1 3
France 34 17 51
Germany 12 3 15
1.Primary Outcome
Title Overall Survival (OS)
Hide Description OS time was measured from date of randomization to date of death from any cause. Participants who were not known to have died on or before the date of data cut-off, OS data was censored on the last date (on or before the cut-off date) the participant was known to be alive.
Time Frame From Date of Randomization to Death from Any Cause (Up to 28 Months)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants. Participants were censored in Ramucirumab arm = 50 and Placebo arm = 21. All randomized participants (including the censored participants) were included in the analyses.
Arm/Group Title Ramucirumab + Best Supportive Care (BSC) Placebo + BSC
Hide Arm/Group Description:
8 milligrams per kilogram (mg/kg) ramucirumab administered as an intravenous (IV) injection on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.

Placebo administered IV on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.

Participants still on treatment at the time of study completion may have the option to crossover to the ramucirumab arm.

Overall Number of Participants Analyzed 197 95
Median (95% Confidence Interval)
Unit of Measure: Months
8.51
(7.00 to 10.58)
7.29
(5.42 to 9.07)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ramucirumab + Best Supportive Care (BSC), Placebo + BSC
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0199
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.710
Confidence Interval (2-Sided) 95%
0.531 to 0.949
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Progression Free Survival (PFS)
Hide Description Progression-free survival is defined as time from the date of randomization to the date of first observation of objective progression or death from any cause. Progressive disease (PD) is referenced as the smallest measurements recorded since the treatment started.
Time Frame From Randomization to Objective Progression or Death from Any Cause (Up to 28 Months)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants. Participants were censored in the Ramucirumab arm = 25 and in the Placebo arm = 9. All randomized participants (including the censored participants) were included in the analyses.
Arm/Group Title Ramucirumab + BSC Placebo + BSC
Hide Arm/Group Description:
8 mg/kg ramucirumab administered as an intravenous IV injection on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.

Placebo administered IV on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.

Participants still on treatment at the time of study completion may have the option to crossover to the ramucirumab arm.

Overall Number of Participants Analyzed 197 95
Median (95% Confidence Interval)
Unit of Measure: Months
2.83
(2.76 to 4.11)
1.61
(1.45 to 2.69)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ramucirumab + BSC, Placebo + BSC
Comments [Not Specified]
Type of Statistical Test Superiority
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 0.452
Confidence Interval (2-Sided) 95%
0.339 to 0.603
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Time to Radiographic Progression
Hide Description Time to radiographic progression is defined as the time from the date of randomization to the date of first observation of objective progression. Progressive disease (PD) is referenced as the smallest measurements recorded since the treatment started.
Time Frame From Randomization to Objective Progression (Up to 28 Months)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants.
Arm/Group Title Ramucirumab + BSC Placebo + BSC
Hide Arm/Group Description:
8 mg/kg ramucirumab administered as an IV injection on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.

Placebo administered IV on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.

Participants still on treatment at the time of study completion may have the option to crossover to the ramucirumab arm.

Overall Number of Participants Analyzed 197 95
Median (95% Confidence Interval)
Unit of Measure: Months
3.02
(2.79 to 4.17)
1.61
(1.45 to 2.73)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ramucirumab + BSC, Placebo + BSC
Comments [Not Specified]
Type of Statistical Test Superiority
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 0.427
Confidence Interval (2-Sided) 95%
0.313 to 0.582
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR): Objective Response Rate (ORR)
Hide Description Objective response rate is defined as the percentage of participants who achieve a best overall response of complete response (CR) + partial response (PR). ORR = CR + PR. CR is the disappearance of all non-target lesions and normalisation of tumour marker level. All lymph nodes must be non-pathological in size (<10 mm short axis). PR is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Tumor marker results must have normalized. Best overall response is classified based on the overall responses assessed by study investigators according to Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1.
Time Frame From Randomization to Objective Progression (Up to 28 Months)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants.
Arm/Group Title Ramucirumab + BSC Placebo + BSC
Hide Arm/Group Description:
8 mg/kg ramucirumab administered as an IV injection on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.

Placebo administered IV on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.

Participants still on treatment at the time of study completion may have the option to crossover to the ramucirumab arm.

Overall Number of Participants Analyzed 197 95
Measure Type: Number
Unit of Measure: percentage of participants
4.6 1.1
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ramucirumab + BSC, Placebo + BSC
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1697
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.6
Confidence Interval (2-Sided) 95%
0.6 to 37.3
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Pharmacokinetics (PK): Minimum Serum Concentration (Cmin) Before 2nd, 4th, 7th, and 10th Infusion
Hide Description PK Cmin of Ramucirumab Blood samples were collected at specified time points, and in the event of an infusion-related reaction, for assessment of ramucirumab serum concentrations.
Time Frame Predose, Weeks 2, 6, 12 and 18, Day 1; Up to 3 Days Before Infusion (14-Day Cycles)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study drug.
Arm/Group Title Ramucirumab + BSC
Hide Arm/Group Description:
8 mg/kg ramucirumab administered as an IV injection on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.
Overall Number of Participants Analyzed 195
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanogram/milliliter (ng/mL)
Week 0
NA [1] 
(NA%)
Week 2
23.5
(57%)
Week 6
44.1
(60%)
Week 12
60.2
(46%)
Week 18
63.2
(40%)
[1]
1 trough concentrations that was reported below the limit of quantitation were treated as missing for the concentration summaries.
6.Secondary Outcome
Title PK: Serum Concentration Maximum (Cmax) After 1st, 2nd, 4th, 7th and 10th Ram Infusion
Hide Description PK Cmax of Ramucirumab Blood samples were collected at specified time points, and in the event of an infusion-related reaction, for assessment of ramucirumab serum concentrations.
Time Frame Weeks 0, 2, 6, 12 and 18, Day 1; 1 hour to 1.5 hours Post End of Infusion (14 day-Cycles)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who had received at least one dose of study drug.
Arm/Group Title Ramucirumab + BSC
Hide Arm/Group Description:
8 mg/kg ramucirumab administered as an IV injection on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.
Overall Number of Participants Analyzed 195
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Week 0
156
(22%)
Week 2
181
(24%)
Week 6
205
(24%)
Week 12
221
(24%)
Week 18
228
(22%)
7.Secondary Outcome
Title Percentage of Participants With Anti-Ramucirumab Antibodies
Hide Description Percentage of participants with positive treatment emergent anti-drug antibodies was summarized by treatment group. A treatment-emergent ADA (TEADA) was defined as: having a negative ADA at baseline and an ADA titer greater than or equal to 1:20 (that is (i.e.), greater than 2-fold from the minimal required dilution of 1:10) any time post baseline (i.e., treatment-induced); or a 4-fold or greater change in ADA titer from baseline for participants that had a detectable ADA titer at baseline (i.e., treatment boosted).
Time Frame Predose Cycle 1: 7 Days prior to First Infusion, Cycle 4: 3 Days Prior to Infusion, Cycle 7 through Follow Up (Up to 28 Months)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study drug and had evaluable anti-ramucirumab data.
Arm/Group Title Ramucirumab + BSC Placebo + BSC
Hide Arm/Group Description:
8 mg/kg ramucirumab administered as an IV injection on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.

Placebo administered IV on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.

Participants still on treatment at the time of study completion may have the option to crossover to the ramucirumab arm.

Overall Number of Participants Analyzed 161 76
Measure Type: Number
Unit of Measure: percentage of participants
5.0 9.2
8.Secondary Outcome
Title Time to Deterioration of Functional Assessment of Cancer Therapy (FACT) Hepatobiliary Symptom Index-8 (FHSI-8)
Hide Description The FACT Hepatobiliary Symptom Index (FHSI-8) is a instrument with specific focus regarding the most frequent and concerning symptoms experienced by participants with hepatobiliary malignancies, including lack of energy, nausea, pain, weight loss, pain in back, fatigue, jaundice, stomach pain or discomfort. The (FHSI-8) questionnaire was used to assess the time to deterioration of FSHI-8 total score issued from the date of randomization to the first date observing deterioration, with the deterioration threshold defined as a decrease ≥ 3-points from baseline. In case of no deterioration, the participants were censored at the time of the last FSHI-8 item recording. FHSI-8 total score ranges from 0 to 32 where "0" is a severely symptomatic participant and the highest score indicates an asymptomatic participant. Kaplan-Meier method Hazard ratio was used to estimate (Ramucirumab versus Placebo) and 95% Confidence Interval (CI) (Wald) were estimated from un-stratified/stratified Cox model.
Time Frame From Randomization to the First Date of Deterioration Observation (≥ 3-point decrease) (Up to 28 Months)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who had evaluable FHSI-8 data.
Arm/Group Title Ramucirumab + BSC Placebo + BSC
Hide Arm/Group Description:
8 mg/kg ramucirumab administered as an IV injection on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.

Placebo administered IV on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.

Participants still on treatment at the time of study completion may have the option to crossover to the ramucirumab arm.

Overall Number of Participants Analyzed 197 95
Median (95% Confidence Interval)
Unit of Measure: Months
3.71
(2.79 to 4.40)
2.79
(1.64 to 2.89)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ramucirumab + BSC, Placebo + BSC
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2382
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.799
Confidence Interval (2-Sided) 95%
0.545 to 1.171
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Change From Baseline in EuroQol 5-Dimension 5-Level (EQ-5D-5L) Questionnaire
Hide Description The EQ-5D-5L is a nonspecific and standardized instrument for use as a measure of self-reported health status (EuroQol Group 1990; Herdman et al. 2011). Participants completed the 5-level (no problems, slight problems, moderate problems, severe problems, and extreme problems), 5-dimension (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) questionnaire concerning their current health state. A unique EQ-5D-5L health state scale ranges from 0 to 100 and is defined by combining 1 level from each of the 5 dimensions. Participants indicated their current health status by marking on a continuum ranging from 100 (best imaginable health state) to 0 (worst imaginable health state).
Time Frame From Randomization through End of Study (Up to 28 Months)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants and had evaluable EQ-5D-5L data.
Arm/Group Title Ramucirumab + BSC Placebo + BSC
Hide Arm/Group Description:
8 mg/kg ramucirumab administered as an IV injection on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.

Placebo administered IV on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.

Participants still on treatment at the time of study completion may have the option to crossover to the ramucirumab arm.

Overall Number of Participants Analyzed 197 95
Mean (Standard Deviation)
Unit of Measure: units on a scale
-0.105  (0.201) -0.099  (0.170)
10.Secondary Outcome
Title Time to Deterioration in Eastern Cooperative Oncology Group Performance Status (ECOG PS)
Hide Description Time to deterioration in ECOG PS is defined as the time from the date of randomization to the first date observing ECOG PS 2 (ie, deterioration from baseline status of 0 [fully active] or 1 [restricted in physically strenuous activity but ambulatory and able to carry out light work]). Participants without PS deterioration were censored at their last documented assessments of 0 or 1. Assessments included ECOG Performance Status (PS): 2- Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours, 3 -Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours, 4 -Completely disabled, cannot carry on any self-care. Totally confined to bed or chair, 5- Dead.
Time Frame From Randomization through First Date of Deterioration Observation (ECOG PS≥2) (Up to 28 Months)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants and had evaluable ECOG data. Censored participants without any post baseline assessments at randomization date were in the Ramucirumab + BSC arm = 141 and the Placebo + BSC arm =75. All randomized participants (including the censored participants) were included in the analyses.
Arm/Group Title Ramucirumab + BSC Placebo + BSC
Hide Arm/Group Description:
8 mg/kg ramucirumab administered as an IV injection on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.

Placebo administered IV on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.

Participants still on treatment at the time of study completion may have the option to crossover to the ramucirumab arm.

Overall Number of Participants Analyzed 197 95
Median (95% Confidence Interval)
Unit of Measure: Months
NA [1] 
(9.33 to NA)
NA [2] 
(5.26 to NA)
[1]
The median and upper limit 95% confidence interval upper limit had insufficient events to perform a meaningful statistical evaluation.
[2]
The median and upper limit 95% confidence interval had insufficient events to perform a meaningful statistical evaluation.
Time Frame Up to 28 Months
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Ramucirumab Placebo
Hide Arm/Group Description 8 milligrams per kilogram (mg/kg) ramucirumab administered as an intravenous (IV) injection on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.

Placebo administered IV on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.

Participants still on treatment at the time of study completion may have the option to crossover to the ramucirumab arm.

All-Cause Mortality
Ramucirumab Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   147/195 (75.38%)      74/95 (77.89%)    
Hide Serious Adverse Events
Ramucirumab Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   68/197 (34.52%)      28/95 (29.47%)    
Blood and lymphatic system disorders     
Neutropenia  1  1/197 (0.51%)  1 0/95 (0.00%)  0
Splenic infarction  1  1/197 (0.51%)  1 0/95 (0.00%)  0
Cardiac disorders     
Angina pectoris  1  1/197 (0.51%)  1 0/95 (0.00%)  0
Myocardial infarction  1  1/197 (0.51%)  1 1/95 (1.05%)  1
Gastrointestinal disorders     
Abdominal hernia  1  1/197 (0.51%)  1 0/95 (0.00%)  0
Abdominal pain  1  3/197 (1.52%)  3 0/95 (0.00%)  0
Abdominal pain upper  1  1/197 (0.51%)  1 0/95 (0.00%)  0
Ascites  1  6/197 (3.05%)  6 0/95 (0.00%)  0
Colitis  1  1/197 (0.51%)  1 0/95 (0.00%)  0
Constipation  1  0/197 (0.00%)  0 1/95 (1.05%)  1
Enterocolitis  1  0/197 (0.00%)  0 1/95 (1.05%)  1
Gastric haemorrhage  1  1/197 (0.51%)  1 0/95 (0.00%)  0
Gastric perforation  1  1/197 (0.51%)  1 0/95 (0.00%)  0
Gastric ulcer  1  1/197 (0.51%)  1 0/95 (0.00%)  0
Gastroduodenal ulcer  1  1/197 (0.51%)  1 0/95 (0.00%)  0
Gastrointestinal haemorrhage  1  0/197 (0.00%)  0 1/95 (1.05%)  1
Lower gastrointestinal haemorrhage  1  1/197 (0.51%)  1 0/95 (0.00%)  0
Melaena  1  0/197 (0.00%)  0 1/95 (1.05%)  1
Nausea  1  0/197 (0.00%)  0 1/95 (1.05%)  1
Oesophageal haemorrhage  1  1/197 (0.51%)  1 0/95 (0.00%)  0
Oesophageal varices haemorrhage  1  2/197 (1.02%)  2 1/95 (1.05%)  1
Rectal haemorrhage  1  1/197 (0.51%)  1 0/95 (0.00%)  0
Upper gastrointestinal haemorrhage  1  1/197 (0.51%)  1 0/95 (0.00%)  0
Varices oesophageal  1  1/197 (0.51%)  1 0/95 (0.00%)  0
General disorders     
Asthenia  1  1/197 (0.51%)  1 0/95 (0.00%)  0
General physical health deterioration  1  1/197 (0.51%)  1 0/95 (0.00%)  0
Generalised oedema  1  1/197 (0.51%)  1 0/95 (0.00%)  0
Multiple organ dysfunction syndrome  1  1/197 (0.51%)  1 0/95 (0.00%)  0
Oedema peripheral  1  2/197 (1.02%)  2 0/95 (0.00%)  0
Pyrexia  1  2/197 (1.02%)  2 1/95 (1.05%)  1
Hepatobiliary disorders     
Acute hepatic failure  1  1/197 (0.51%)  1 0/95 (0.00%)  0
Cholestasis  1  0/197 (0.00%)  0 1/95 (1.05%)  1
Hepatorenal syndrome  1  2/197 (1.02%)  3 0/95 (0.00%)  0
Jaundice  1  1/197 (0.51%)  1 1/95 (1.05%)  1
Immune system disorders     
Anaphylactic reaction  1  1/197 (0.51%)  1 0/95 (0.00%)  0
Infections and infestations     
Anal abscess  1  1/197 (0.51%)  1 0/95 (0.00%)  0
Appendicitis  1  1/197 (0.51%)  1 1/95 (1.05%)  1
Gastroenteritis  1  1/197 (0.51%)  1 0/95 (0.00%)  0
Infection  1  0/197 (0.00%)  0 1/95 (1.05%)  2
Influenza  1  2/197 (1.02%)  2 0/95 (0.00%)  0
Lower respiratory tract infection  1  2/197 (1.02%)  2 0/95 (0.00%)  0
Lung infection  1  0/197 (0.00%)  0 1/95 (1.05%)  1
Peritonitis  1  1/197 (0.51%)  1 2/95 (2.11%)  2
Pleural infection  1  1/197 (0.51%)  1 0/95 (0.00%)  0
Pneumonia  1  5/197 (2.54%)  5 2/95 (2.11%)  3
Post procedural infection  1  1/197 (0.51%)  1 0/95 (0.00%)  0
Respiratory tract infection  1  0/197 (0.00%)  0 1/95 (1.05%)  1
Sepsis  1  3/197 (1.52%)  3 3/95 (3.16%)  3
Septic shock  1  0/197 (0.00%)  0 1/95 (1.05%)  1
Urinary tract infection  1  1/197 (0.51%)  1 0/95 (0.00%)  0
Injury, poisoning and procedural complications     
Ankle fracture  1  0/197 (0.00%)  0 1/95 (1.05%)  1
Fall  1  1/197 (0.51%)  1 0/95 (0.00%)  0
Hip fracture  1  1/197 (0.51%)  1 0/95 (0.00%)  0
Infusion related reaction  1  0/197 (0.00%)  0 1/95 (1.05%)  1
Investigations     
Aspiration pleural cavity  1  1/197 (0.51%)  1 0/95 (0.00%)  0
Blood bilirubin increased  1  0/197 (0.00%)  0 1/95 (1.05%)  1
General physical condition abnormal  1  1/197 (0.51%)  2 0/95 (0.00%)  0
Metabolism and nutrition disorders     
Dehydration  1  1/197 (0.51%)  1 0/95 (0.00%)  0
Hypercalcaemia  1  0/197 (0.00%)  0 1/95 (1.05%)  2
Musculoskeletal and connective tissue disorders     
Back pain  1  1/197 (0.51%)  1 0/95 (0.00%)  0
Muscular weakness  1  1/197 (0.51%)  1 0/95 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Liver carcinoma ruptured  1  0/197 (0.00%)  0 1/95 (1.05%)  1
Metastases to bone  1  1/197 (0.51%)  1 0/95 (0.00%)  0
Metastases to spine  1  1/197 (0.51%)  1 1/95 (1.05%)  1
Tumour haemorrhage  1  1/197 (0.51%)  1 0/95 (0.00%)  0
Tumour pain  1  1/197 (0.51%)  1 0/95 (0.00%)  0
Tumour rupture  1  1/197 (0.51%)  1 0/95 (0.00%)  0
Nervous system disorders     
Cerebral ischaemia  1  1/197 (0.51%)  1 0/95 (0.00%)  0
Cerebrovascular accident  1  1/197 (0.51%)  1 0/95 (0.00%)  0
Coma hepatic  1  1/197 (0.51%)  1 0/95 (0.00%)  0
Epilepsy  1  1/197 (0.51%)  1 0/95 (0.00%)  0
Hepatic encephalopathy  1  3/197 (1.52%)  3 0/95 (0.00%)  0
Somnolence  1  1/197 (0.51%)  1 0/95 (0.00%)  0
Psychiatric disorders     
Anxiety  1  0/197 (0.00%)  0 1/95 (1.05%)  1
Confusional state  1  1/197 (0.51%)  1 0/95 (0.00%)  0
Renal and urinary disorders     
Acute kidney injury  1  3/197 (1.52%)  3 0/95 (0.00%)  0
Nephrotic syndrome  1  1/197 (0.51%)  1 0/95 (0.00%)  0
Renal failure  1  1/197 (0.51%)  1 0/95 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1  3/197 (1.52%)  3 3/95 (3.16%)  3
Epistaxis  1  1/197 (0.51%)  1 0/95 (0.00%)  0
Haemothorax  1  1/197 (0.51%)  1 0/95 (0.00%)  0
Lung disorder  1  0/197 (0.00%)  0 1/95 (1.05%)  1
Pleural effusion  1  0/197 (0.00%)  0 1/95 (1.05%)  1
Pulmonary oedema  1  0/197 (0.00%)  0 1/95 (1.05%)  1
Vascular disorders     
Deep vein thrombosis  1  0/197 (0.00%)  0 1/95 (1.05%)  1
Haemorrhage  1  0/197 (0.00%)  0 1/95 (1.05%)  1
Hypertensive crisis  1  1/197 (0.51%)  1 0/95 (0.00%)  0
Trousseau's syndrome  1  1/197 (0.51%)  1 0/95 (0.00%)  0
1
Term from vocabulary, MedDRA 20.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Ramucirumab Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   189/197 (95.94%)      77/95 (81.05%)    
Blood and lymphatic system disorders     
Anaemia  1  17/197 (8.63%)  26 6/95 (6.32%)  7
Gastrointestinal disorders     
Abdominal distension  1  15/197 (7.61%)  17 5/95 (5.26%)  6
Abdominal pain  1  36/197 (18.27%)  46 12/95 (12.63%)  16
Ascites  1  34/197 (17.26%)  46 7/95 (7.37%)  7
Constipation  1  27/197 (13.71%)  32 18/95 (18.95%)  19
Diarrhoea  1  32/197 (16.24%)  43 14/95 (14.74%)  18
Nausea  1  37/197 (18.78%)  47 10/95 (10.53%)  12
Vomiting  1  20/197 (10.15%)  23 7/95 (7.37%)  7
General disorders     
Asthenia  1  17/197 (8.63%)  41 3/95 (3.16%)  6
Chills  1  0/197 (0.00%)  0 5/95 (5.26%)  6
Fatigue  1  54/197 (27.41%)  78 16/95 (16.84%)  23
Influenza like illness  1  10/197 (5.08%)  10 1/95 (1.05%)  1
Malaise  1  14/197 (7.11%)  15 5/95 (5.26%)  6
Oedema peripheral  1  50/197 (25.38%)  67 13/95 (13.68%)  13
Pyrexia  1  18/197 (9.14%)  21 3/95 (3.16%)  3
Infections and infestations     
Urinary tract infection  1  10/197 (5.08%)  17 1/95 (1.05%)  2
Investigations     
Alanine aminotransferase increased  1  7/197 (3.55%)  12 5/95 (5.26%)  6
Aspartate aminotransferase increased  1  16/197 (8.12%)  27 10/95 (10.53%)  15
Blood bilirubin increased  1  21/197 (10.66%)  39 8/95 (8.42%)  16
Gamma-glutamyltransferase increased  1  2/197 (1.02%)  2 5/95 (5.26%)  6
Neutrophil count decreased  1  12/197 (6.09%)  28 0/95 (0.00%)  0
Platelet count decreased  1  22/197 (11.17%)  60 2/95 (2.11%)  3
Weight decreased  1  19/197 (9.64%)  22 6/95 (6.32%)  7
Metabolism and nutrition disorders     
Decreased appetite  1  46/197 (23.35%)  57 19/95 (20.00%)  19
Hyperkalaemia  1  13/197 (6.60%)  21 3/95 (3.16%)  3
Hypoalbuminaemia  1  20/197 (10.15%)  28 4/95 (4.21%)  4
Hyponatraemia  1  11/197 (5.58%)  16 1/95 (1.05%)  1
Musculoskeletal and connective tissue disorders     
Back pain  1  20/197 (10.15%)  23 7/95 (7.37%)  8
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Tumour pain  1  4/197 (2.03%)  4 8/95 (8.42%)  9
Nervous system disorders     
Dizziness  1  9/197 (4.57%)  10 8/95 (8.42%)  8
Headache  1  28/197 (14.21%)  36 5/95 (5.26%)  5
Psychiatric disorders     
Insomnia  1  21/197 (10.66%)  24 6/95 (6.32%)  8
Renal and urinary disorders     
Proteinuria  1  40/197 (20.30%)  66 4/95 (4.21%)  4
Respiratory, thoracic and mediastinal disorders     
Cough  1  18/197 (9.14%)  21 6/95 (6.32%)  7
Dysphonia  1  10/197 (5.08%)  10 1/95 (1.05%)  1
Dyspnoea  1  15/197 (7.61%)  18 8/95 (8.42%)  9
Epistaxis  1  26/197 (13.20%)  30 3/95 (3.16%)  3
Skin and subcutaneous tissue disorders     
Pruritus  1  15/197 (7.61%)  16 5/95 (5.26%)  5
Rash  1  13/197 (6.60%)  18 5/95 (5.26%)  5
Vascular disorders     
Hypertension  1  48/197 (24.37%)  75 12/95 (12.63%)  13
1
Term from vocabulary, MedDRA 20.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
Phone: (800) 545-5979
EMail: ClinicalTrials.gov@Lilly.com
Layout table for additonal information
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT02435433    
Other Study ID Numbers: 15755
I4T-MC-JVDE ( Other Identifier: Eli Lilly and Company )
2014-005068-13 ( EudraCT Number )
First Submitted: May 1, 2015
First Posted: May 6, 2015
Results First Submitted: April 8, 2019
Results First Posted: May 17, 2019
Last Update Posted: December 16, 2019