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A Study of Chemotherapy and Ramucirumab Versus Chemotherapy Alone in Second Line Non-Small Cell Lung Cancer (NSCLC) Participants Who Received Prior First Line Platinum-based Chemotherapy

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ClinicalTrials.gov Identifier: NCT01168973
Recruitment Status : Completed
First Posted : July 23, 2010
Results First Posted : December 29, 2014
Last Update Posted : September 25, 2019
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Non-Small Cell Lung Cancer
Interventions Biological: Ramucirumab
Drug: Placebo (for Ramucirumab)
Drug: Docetaxel
Enrollment 1253
Recruitment Details  
Pre-assignment Details Participants who died, due to any cause, or were alive at the end of the study but off study drug were considered to have completed the study.
Arm/Group Title Ramucirumab and Docetaxel Placebo and Docetaxel
Hide Arm/Group Description

On Day 1 of each 21-day cycle, participants received ramucirumab drug product (DP) followed by docetaxel. Treatment continued until disease progression, unacceptable toxicity, or other withdrawal criteria were met.

  • Ramucirumab DP: 10 milligrams per kilogram (mg/kg) administered intravenously.
  • Docetaxel: 75 milligrams per square meter (mg/m^2) (60 mg/m^2 for the countries of Korea and Taiwan only, with protocol amendment dated 22 May 2012) administered intravenously.

On Day 1 of each 21-day cycle, participants received placebo followed by docetaxel. Treatment continued until disease progression, unacceptable toxicity, or other withdrawal criteria were met.

  • Placebo (matching Ramucirumab DP): 10 mg/kg administered intravenously.
  • Docetaxel: 75 mg/m^2 (60 mg/m^2 for the countries of Korea and Taiwan only, with protocol amendment dated 22 May 2012) administered intravenously.
Period Title: Overall Study
Started 628 625
Received Any Quantity of Any Study Drug 624 621 [1]
Completed 15 14
Not Completed 613 611
Reason Not Completed
Progressive Disease             341             429
Adverse Event             94             55
Withdrawal by Subject             90             53
Death             42             45
Physician Decision             37             19
Sponsor Decision             2             1
Protocol Criterion Not Met and Deviation             7             9
[1]
Three participants randomized to placebo and docetaxel received 1 dose of ramucirumab in error.
Arm/Group Title Ramucirumab and Docetaxel Placebo and Docetaxel Total
Hide Arm/Group Description

On Day 1 of each 21-day cycle, participants received ramucirumab DP followed by docetaxel. Treatment continued until disease progression, unacceptable toxicity, or other withdrawal criteria were met.

  • Ramucirumab DP: 10 mg/kg administered intravenously.
  • Docetaxel: 75 mg/m^2 (60 mg/m^2 for the countries of Korea and Taiwan only, with protocol amendment dated 22 May 2012) administered intravenously.

On Day 1 of each 21-day cycle, participants received placebo followed by docetaxel. Treatment continued until disease progression, unacceptable toxicity, or other withdrawal criteria were met.

  • Placebo (matching Ramucirumab DP): 10 mg/kg administered intravenously.
  • Docetaxel: 75 mg/m^2 (60 mg/m^2 for the countries of Korea and Taiwan only, with protocol amendment dated 22 May 2012) administered intravenously.
Total of all reporting groups
Overall Number of Baseline Participants 628 625 1253
Hide Baseline Analysis Population Description
Intent-to-Treat (ITT) population: All randomized participants grouped according to their assigned treatment at randomization.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 628 participants 625 participants 1253 participants
<=18 years 0 0 0
Between 18 and 65 years 391 407 798
>=65 years 237 218 455
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 628 participants 625 participants 1253 participants
Female 209 210 419
Male 419 415 834
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 628 participants 625 participants 1253 participants
Hispanic or Latino 43 53 96
Not Hispanic or Latino 387 380 767
Unknown or Not Reported 198 192 390
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 628 participants 625 participants 1253 participants
American Indian or Alaska Native 9 20 29
Asian 74 86 160
Native Hawaiian or Other Pacific Islander 1 0 1
Black or African American 17 16 33
White 526 503 1029
More than one race 0 0 0
Unknown or Not Reported 1 0 1
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 628 participants 625 participants 1253 participants
United States 156 152 308
Taiwan 9 18 27
Greece 25 19 44
Spain 27 23 50
Israel 14 8 22
Russian Federation 28 33 61
Italy 26 28 54
Switzerland 12 14 26
India 22 33 55
France 21 24 45
Puerto Rico 1 2 3
Netherlands 15 16 31
Korea, Republic of 34 28 62
Turkey 22 23 45
Austria 11 9 20
United Kingdom 19 19 38
Hungary 9 4 13
Mexico 11 20 31
Canada 12 7 19
Argentina 16 17 33
Brazil 4 3 7
Poland 30 33 63
Romania 41 36 77
Norway 10 3 13
Germany 40 42 82
New Zealand 3 4 7
Sweden 10 7 17
1.Primary Outcome
Title Overall Survival
Hide Description Overall survival was the time from randomization until the date of death from any cause. Participants who were alive at the end of the follow-up period (or lost to follow-up) were censored on the last date the participant was known to be alive.
Time Frame Randomization to date of death from any cause (up to 34 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) population: All randomized participants grouped according to their assigned treatment at randomization. Participants censored: ramucirumab and docetaxel arm = 200 participants; placebo and docetaxel arm = 169 participants.
Arm/Group Title Ramucirumab and Docetaxel Placebo and Docetaxel
Hide Arm/Group Description:

On Day 1 of each 21-day cycle, participants received ramucirumab DP followed by docetaxel. Treatment continued until disease progression, unacceptable toxicity, or other withdrawal criteria were met.

  • Ramucirumab DP: 10 mg/kg administered intravenously.
  • Docetaxel: 75 mg/m^2 (60 mg/m^2 for the countries of Korea and Taiwan only, with protocol amendment dated 22 May 2012) administered intravenously.

On Day 1 of each 21-day cycle, participants received placebo followed by docetaxel. Treatment continued until disease progression, unacceptable toxicity, or other withdrawal criteria were met.

  • Placebo (matching Ramucirumab DP): 10 mg/kg administered intravenously.
  • Docetaxel: 75 mg/m^2 (60 mg/m^2 for the countries of Korea and Taiwan only, with protocol amendment dated 22 May 2012) administered intravenously.
Overall Number of Participants Analyzed 628 625
Median (95% Confidence Interval)
Unit of Measure: months
10.5
(9.5 to 11.2)
9.1
(8.4 to 10.0)
2.Secondary Outcome
Title Progression-Free Survival (PFS) Time
Hide Description PFS time was the time from randomization until the date of objectively determined progressive disease (PD) or death due to any cause, whichever occurred first. According to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), PD was at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. In addition to the 20% relative increase, the sum must have also demonstrated an absolute increase of at least 5 millimeters (mm). The appearance of 1 or more new lesions and/or unequivocal progression of existing nontarget lesions was also considered progression. Participants without objectively determined PD who were alive at the end of the follow-up period (or lost to follow-up) were censored on the date of the participant's last complete radiographic tumor assessment; if no baseline or post-baseline radiologic assessment was available, the participant was censored at the date of randomization.
Time Frame Randomization to measured PD or date of death from any cause (up to 29 months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population: All randomized participants grouped according to their assigned treatment at randomization. Participants censored: ramucirumab and docetaxel arm = 70 participants; placebo and docetaxel arm = 42 participants.
Arm/Group Title Ramucirumab and Docetaxel Placebo and Docetaxel
Hide Arm/Group Description:

On Day 1 of each 21-day cycle, participants received ramucirumab DP followed by docetaxel. Treatment continued until disease progression, unacceptable toxicity, or other withdrawal criteria were met.

  • Ramucirumab DP: 10 mg/kg administered intravenously.
  • Docetaxel: 75 mg/m^2 (60 mg/m^2 for the countries of Korea and Taiwan only, with protocol amendment dated 22 May 2012) administered intravenously.

On Day 1 of each 21-day cycle, participants received placebo followed by docetaxel. Treatment continued until disease progression, unacceptable toxicity, or other withdrawal criteria were met.

  • Placebo (matching Ramucirumab DP): 10 mg/kg administered intravenously.
  • Docetaxel: 75 mg/m^2 (60 mg/m^2 for the countries of Korea and Taiwan only, with protocol amendment dated 22 May 2012) administered intravenously.
Overall Number of Participants Analyzed 628 625
Median (95% Confidence Interval)
Unit of Measure: months
4.5
(4.2 to 5.3)
3.0
(2.8 to 3.9)
3.Secondary Outcome
Title Percentage of Participants Achieving an Objective Response (Objective Response Rate)
Hide Description Participants achieved an objective response if they had a best overall response of partial response (PR) or complete response (CR). According to RECIST v1.1, PR was defined as at least a 30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph node), taking as reference the baseline sum diameter; CR was the disappearance of all non-nodal target lesions, with the short axes of any target lymph node reduced to <10 mm, the disappearance of all nontarget lesions, and the normalization of tumor marker levels [if tumor markers were initially above the upper limit of normal (ULN)]. The percentage of participants who achieved an objective response=(number of participants with CR or PR)/(number of participants assessed)*100.
Time Frame Baseline to measured PD (up to 29 months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population: All randomized participants grouped according to their assigned treatment at randomization.
Arm/Group Title Ramucirumab and Docetaxel Placebo and Docetaxel
Hide Arm/Group Description:

On Day 1 of each 21-day cycle, participants received ramucirumab DP followed by docetaxel. Treatment continued until disease progression, unacceptable toxicity, or other withdrawal criteria were met.

  • Ramucirumab DP: 10 mg/kg administered intravenously.
  • Docetaxel: 75 mg/m^2 (60 mg/m^2 for the countries of Korea and Taiwan only, with protocol amendment dated 22 May 2012) administered intravenously.

On Day 1 of each 21-day cycle, participants received placebo followed by docetaxel. Treatment continued until disease progression, unacceptable toxicity, or other withdrawal criteria were met.

  • Placebo (matching Ramucirumab DP): 10 mg/kg administered intravenously.
  • Docetaxel: 75 mg/m^2 (60 mg/m^2 for the countries of Korea and Taiwan only, with protocol amendment dated 22 May 2012) administered intravenously.
Overall Number of Participants Analyzed 628 625
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
22.9
(19.7 to 26.4)
13.6
(11.0 to 16.5)
4.Secondary Outcome
Title Percentage of Participants Achieving Disease Control (Disease Control Rate)
Hide Description Participants achieved disease control if they had a best overall response of PR, CR or stable disease (SD). According to RECIST v1.1, PR was defined as at least a 30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph node), taking as reference the baseline sum diameter; CR was the disappearance of all non-nodal target lesions, with the short axes of any target lymph node reduced to <10 mm, the disappearance of all nontarget lesions, and the normalization of tumor marker levels (if tumor markers were initially above the ULN). SD was neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD, taking as reference the smallest sum diameter since treatment started. The percentage of participants who achieved disease control=(number of participants with CR, PR, or SD)/(number of participants assessed)*100.
Time Frame Baseline to measured PD (up to 29 months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population: All randomized participants grouped according to their assigned treatment at randomization.
Arm/Group Title Ramucirumab and Docetaxel Placebo and Docetaxel
Hide Arm/Group Description:

On Day 1 of each 21-day cycle, participants received ramucirumab DP followed by docetaxel. Treatment continued until disease progression, unacceptable toxicity, or other withdrawal criteria were met.

  • Ramucirumab DP: 10 mg/kg administered intravenously.
  • Docetaxel: 75 mg/m^2 (60 mg/m^2 for the countries of Korea and Taiwan only, with protocol amendment dated 22 May 2012) administered intravenously.

On Day 1 of each 21-day cycle, participants received placebo followed by docetaxel. Treatment continued until disease progression, unacceptable toxicity, or other withdrawal criteria were met.

  • Placebo (matching Ramucirumab DP): 10 mg/kg administered intravenously.
  • Docetaxel: 75 mg/m^2 (60 mg/m^2 for the countries of Korea and Taiwan only, with protocol amendment dated 22 May 2012) administered intravenously.
Overall Number of Participants Analyzed 628 625
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
64.0
(60.1 to 67.8)
52.6
(48.6 to 56.6)
5.Secondary Outcome
Title Maximum Improvement on Lung Cancer Symptom Scale (LCSS)
Hide Description The LCSS consisted of 9 items: 6 items focused on lung cancer symptoms [loss of appetite, fatigue, cough, dyspnea (shortness of breath), hemoptysis (blood in sputum), and pain] and 3 items were global items (symptom distress, interference with activity level, and global quality of life). Participant responses to each item were measured using visual analogue scales (VAS) with 100-mm lines. A higher score for any item represented a higher level of symptoms/problems. The Average Symptom Burden Index (ASBI) was the mean of the 6 symptom items of the LCSS, and the Total LCSS was the mean of all 9 LCSS items. ASBI and Total LCSS were not computed for a participant if he/she had 1 or more missing values for the 6 and 9 items, respectively. Maximum improvement in LCSS scores, ASBI, and Total LCSS score was the largest decrease from baseline for each variable, which was the smallest (most negative or smallest positive) non-missing value among all change from baseline values for each variable.
Time Frame Baseline, Day 21 of each cycle, and 30 days following last infusion (up to Cycle 38, 21 days/cycle)
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants grouped according to their assigned treatment at randomization, who had a baseline and at least 1 post-baseline LCSS score.
Arm/Group Title Ramucirumab and Docetaxel Placebo and Docetaxel
Hide Arm/Group Description:

On Day 1 of each 21-day cycle, participants received ramucirumab DP followed by docetaxel. Treatment continued until disease progression, unacceptable toxicity, or other withdrawal criteria were met.

  • Ramucirumab DP: 10 mg/kg administered intravenously.
  • Docetaxel: 75 mg/m^2 (60 mg/m^2 for the countries of Korea and Taiwan only, with protocol amendment dated 22 May 2012) administered intravenously.

On Day 1 of each 21-day cycle, participants received placebo followed by docetaxel. Treatment continued until disease progression, unacceptable toxicity, or other withdrawal criteria were met.

  • Placebo (matching Ramucirumab DP): 10 mg/kg administered intravenously.
  • Docetaxel: 75 mg/m^2 (60 mg/m^2 for the countries of Korea and Taiwan only, with protocol amendment dated 22 May 2012) administered intravenously.
Overall Number of Participants Analyzed 476 477
Mean (Standard Deviation)
Unit of Measure: mm
Loss of Appetite (n=473, 471) -10.9  (26.11) -11.0  (26.22)
Fatigue (n=473, 472) -12.1  (23.86) -12.0  (27.29)
Cough (n=476, 473) -13.8  (24.28) -14.3  (26.28)
Dyspnea (n=472, 477) -11.0  (23.01) -10.5  (24.31)
Hemoptysis (n=475, 475) -1.4  (8.89) -1.1  (8.79)
Pain (n=476, 475) -11.3  (23.62) -11.5  (24.85)
Symptom Distress (n=474, 472) -10.7  (23.37) -12.2  (26.25)
Interference With Activity Level (n=474, 472) -8.5  (24.13) -7.9  (24.95)
Global Quality of Life (n=467, 469) -10.4  (22.68) -8.9  (23.23)
ASBI (n=455, 456) -6.1  (13.75) -6.9  (14.50)
Total LCSS (n=446, 446) -5.2  (13.75) -6.4  (14.66)
6.Secondary Outcome
Title Change From Baseline to 30-Day Follow-Up Visit on European Quality of Life Questionnaire-5 Dimension (EQ-5D) Health State Scores
Hide Description The EQ-5D is a quality-of-life instrument that consists of 2 parts. The first part (Health State Index score) allowed participants to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression using a scale from 1 to 3 (no problem, some problems, and extreme problems, respectively). These combinations of attributes were converted into a weighted Health State Index score according to a United Kingdom population-based algorithm; the possible values for the Health State Index score ranged from -0.59 (severe problems in all 5 dimensions) to 1.0 (no problem in any dimension). The second part of the EQ-5D was a VAS that allowed participants to rate their present health condition. Possible EQ-5D VAS scores ranged from 0 (worst imaginable health state) to 100 (best imaginable health state).
Time Frame Baseline, 30 days following last infusion (up to Cycle 38, 21 days/cycle)
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants grouped according to their assigned treatment at randomization, who had an EQ-5D assessment at a baseline and 30 days post treatment.
Arm/Group Title Ramucirumab and Docetaxel Placebo and Docetaxel
Hide Arm/Group Description:

On Day 1 of each 21-day cycle, participants received ramucirumab DP followed by docetaxel. Treatment continued until disease progression, unacceptable toxicity, or other withdrawal criteria were met.

  • Ramucirumab DP: 10 mg/kg administered intravenously.
  • Docetaxel: 75 mg/m^2 (60 mg/m^2 for the countries of Korea and Taiwan only, with protocol amendment dated 22 May 2012) administered intravenously.

On Day 1 of each 21-day cycle, participants received placebo followed by docetaxel. Treatment continued until disease progression, unacceptable toxicity, or other withdrawal criteria were met.

  • Placebo (matching Ramucirumab DP): 10 mg/kg administered intravenously.
  • Docetaxel: 75 mg/m^2 (60 mg/m^2 for the countries of Korea and Taiwan only, with protocol amendment dated 22 May 2012) administered intravenously.
Overall Number of Participants Analyzed 272 272
Mean (Standard Deviation)
Unit of Measure: units on a scale
Health State Index Score (n=266, 272) -0.140  (0.308) -0.126  (0.294)
Health State VAS Score (n=272, 254) -5.9  (21.02) -6.1  (20.31)
7.Secondary Outcome
Title Maximum and Minimum Serum Concentrations (Cmax and Cmin) of Ramucirumab
Hide Description [Not Specified]
Time Frame Prior to infusion and 1 hour following infusion for 4 and 8 (cycles 3 and 5 at 21 days/cycle)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants assigned to the ramucirumab and docetaxel arm at randomization, who had evaluable ramucirumab pharmacokinetic (PK) data to calculate Cmax and Cmin.
Arm/Group Title Ramucirumab and Docetaxel
Hide Arm/Group Description:

On Day 1 of each 21-day cycle, participants received ramucirumab DP followed by docetaxel. Treatment continued until disease progression, unacceptable toxicity, or other withdrawal criteria were met.

  • Ramucirumab DP: 10 mg/kg administered intravenously.
  • Docetaxel: 75 mg/m^2 (60 mg/m^2 for the countries of Korea and Taiwan only, with protocol amendment dated 22 May 2012) administered intravenously.
Overall Number of Participants Analyzed 594
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: micrograms per milliliter (mcg/mL)
Cmax at Cycle 3
262
(30%)
Cmin at Cycle 3
28.3
(65%)
Cmax at Cycle 5
237
(38%)
Cmin at Cycle 5
38.4
(63%)
8.Secondary Outcome
Title Number of Participants With Anti-Ramucirumab Antibodies
Hide Description The number of participants who had treatment-emergent or follow-up emergent anti-drug antibodies (ADA) is reported. Participants with treatment-emergent ADA were defined as participants who had any sample from baseline through Cycle 5 pre-infusion that was a 4-fold increase (2 dilution increase) in immunogenicity titer over the baseline titer, or participants who tested negative at baseline and positive post-baseline (at titer of ≥1:20). Participants with follow-up emergent ADA were defined as participants who had any sample during 30 days post last infusion that was a 4-fold increase (2 dilution increase) in immunogenicity titer over the baseline titer.
Time Frame Baseline, prior to infusion for week 4 and 8 (cycles 3 and 5), and 30 days following last infusion (up to Cycle 38, 21 days/cycle)
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received any quantity of study treatment, grouped by the treatment they actually received, who had a baseline and at least 1 post-baseline ADA assessment.
Arm/Group Title Ramucirumab and Docetaxel Placebo and Docetaxel
Hide Arm/Group Description:

On Day 1 of each 21-day cycle, participants received ramucirumab DP followed by docetaxel. Treatment continued until disease progression, unacceptable toxicity, or other withdrawal criteria were met.

  • Ramucirumab DP: 10 mg/kg administered intravenously.
  • Docetaxel: 75 mg/m^2 (60 mg/m^2 for the countries of Korea and Taiwan only, with protocol amendment dated 22 May 2012) administered intravenously.

On Day 1 of each 21-day cycle, participants received placebo followed by docetaxel. Treatment continued until disease progression, unacceptable toxicity, or other withdrawal criteria were met.

  • Placebo (matching Ramucirumab DP): 10 mg/kg administered intravenously.
  • Docetaxel: 75 mg/m^2 (60 mg/m^2 for the countries of Korea and Taiwan only, with protocol amendment dated 22 May 2012) administered intravenously.
Overall Number of Participants Analyzed 599 598
Measure Type: Number
Unit of Measure: participants
Treatment-Emergent ADA (n=599, 598) 9 16
Follow-Up Emergent ADA (n=506, 481) 9 16
9.Other Pre-specified Outcome
Title Number of Participants Who Had Treatment-Emergent Adverse Events (TEAEs) or Died
Hide Description Data presented are the number of participants who experienced at least 1 TEAE, Grade 3, 4, or 5 TEAE, treatment-emergent serious adverse event (SAE), TEAE leading to discontinuation of study treatment (ramucirumab/placebo or docetaxel), and TEAE leading to death. Clinically significant events were defined as treatment-emergent SAEs and other non-serious adverse events (AEs) regardless of causality. A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.
Time Frame First infusion up to 30 days following last infusion (up to Cycle 38, 21 days/cycle)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population: Randomized participants who received any quantity of study drug, grouped by the treatment they actually received.
Arm/Group Title Ramucirumab and Docetaxel Placebo and Docetaxel
Hide Arm/Group Description:

On Day 1 of each 21-day cycle, participants received ramucirumab DP followed by docetaxel. Treatment continued until disease progression, unacceptable toxicity, or other withdrawal criteria were met.

  • Ramucirumab DP: 10 mg/kg administered intravenously.
  • Docetaxel: 75 mg/m^2 (60 mg/m^2 for the countries of Korea and Taiwan only, with protocol amendment dated 22 May 2012) administered intravenously.

On Day 1 of each 21-day cycle, participants received placebo followed by docetaxel. Treatment continued until disease progression, unacceptable toxicity, or other withdrawal criteria were met.

  • Placebo (matching Ramucirumab DP): 10 mg/kg administered intravenously.
  • Docetaxel: 75 mg/m^2 (60 mg/m^2 for the countries of Korea and Taiwan only, with protocol amendment dated 22 May 2012) administered intravenously.
Overall Number of Participants Analyzed 627 618
Measure Type: Number
Unit of Measure: participants
At least 1 TEAE 613 594
At least 1 Grade 3, 4, or 5 TEAE 495 444
At least 1 treatment-emergent SAE 269 262
TEAE leading to study drug discontinuation 58 32
TEAE leading to death 34 35
Deaths While On Treatment 428 451
Deaths During 30 Days Post Last Dose 53 58
Time Frame Randomization through 30 days following last infusion (up to Cycle 38, 21 days/cycle).
Adverse Event Reporting Description

Safety Population: All randomized participants who received any quantity of study treatment, grouped by the treatment they actually received.

Three participants randomized to placebo and docetaxel received 1 dose of ramucirumab in error.

 
Arm/Group Title Ramucirumab and Docetaxel Placebo and Docetaxel
Hide Arm/Group Description

On Day 1 of each 21-day cycle, participants received ramucirumab DP followed by docetaxel. Treatment continued until disease progression, unacceptable toxicity, or other withdrawal criteria were met.

  • Ramucirumab DP: 10 mg/kg administered intravenously.
  • Docetaxel: 75 mg/m^2 (60 mg/m^2 for the countries of Korea and Taiwan only, with protocol amendment dated 22 May 2012) administered intravenously.

On Day 1 of each 21-day cycle, participants received placebo followed by docetaxel. Treatment continued until disease progression, unacceptable toxicity, or other withdrawal criteria were met.

  • Placebo (matching Ramucirumab DP): 10 mg/kg administered intravenously.
  • Docetaxel: 75 mg/m^2 (60 mg/m^2 for the countries of Korea and Taiwan only, with protocol amendment dated 22 May 2012) administered intravenously.
All-Cause Mortality
Ramucirumab and Docetaxel Placebo and Docetaxel
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Hide Serious Adverse Events
Ramucirumab and Docetaxel Placebo and Docetaxel
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   284/627 (45.30%)      281/618 (45.47%)    
Blood and lymphatic system disorders     
Anaemia  1  10/627 (1.59%)  16 14/618 (2.27%)  17
Febrile neutropenia  1  86/627 (13.72%)  104 51/618 (8.25%)  56
Leukopenia  1  5/627 (0.80%)  6 10/618 (1.62%)  14
Neutropenia  1  30/627 (4.78%)  38 27/618 (4.37%)  33
Thrombocytopenia  1  3/627 (0.48%)  3 1/618 (0.16%)  1
Cardiac disorders     
Arrhythmia  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Atrial fibrillation  1  6/627 (0.96%)  6 2/618 (0.32%)  2
Atrial flutter  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Atrial tachycardia  1  2/627 (0.32%)  2 0/618 (0.00%)  0
Cardiac arrest  1  2/627 (0.32%)  2 1/618 (0.16%)  1
Cardiac failure  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Cardiac failure congestive  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Cardiac tamponade  1  1/627 (0.16%)  2 0/618 (0.00%)  0
Cardio-respiratory arrest  1  2/627 (0.32%)  2 2/618 (0.32%)  2
Coronary artery occlusion  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Myocardial infarction  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Pericardial effusion  1  1/627 (0.16%)  2 6/618 (0.97%)  6
Sinus tachycardia  1  1/627 (0.16%)  1 1/618 (0.16%)  1
Supraventricular tachycardia  1  2/627 (0.32%)  2 3/618 (0.49%)  4
Tachycardia  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Ventricular arrhythmia  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Congenital, familial and genetic disorders     
Tracheo-oesophageal fistula  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Eye disorders     
Diplopia  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Retinal vein thrombosis  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Gastrointestinal disorders     
Abdominal pain  1  3/627 (0.48%)  3 7/618 (1.13%)  8
Abdominal pain upper  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Anal fistula  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Anal inflammation  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Ascites  1  1/627 (0.16%)  2 0/618 (0.00%)  0
Colitis  1  2/627 (0.32%)  2 0/618 (0.00%)  0
Constipation  1  0/627 (0.00%)  0 2/618 (0.32%)  2
Diarrhoea  1  13/627 (2.07%)  13 9/618 (1.46%)  9
Diverticular perforation  1  2/627 (0.32%)  2 2/618 (0.32%)  2
Duodenal ulcer  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Dysphagia  1  2/627 (0.32%)  2 3/618 (0.49%)  4
Enteritis  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Enterocolitis  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Gastric haemorrhage  1  1/627 (0.16%)  1 1/618 (0.16%)  1
Gastritis  1  0/627 (0.00%)  0 2/618 (0.32%)  3
Gastrointestinal haemorrhage  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Gastrointestinal inflammation  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Gingival bleeding  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Haematemesis  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Haemorrhoidal haemorrhage  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Ileal fistula  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Ileus  1  2/627 (0.32%)  2 0/618 (0.00%)  0
Ileus paralytic  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Intestinal ischaemia  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Large intestinal obstruction  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Large intestine perforation  1  2/627 (0.32%)  2 0/618 (0.00%)  0
Melaena  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Nausea  1  7/627 (1.12%)  8 1/618 (0.16%)  2
Neutropenic colitis  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Oesophageal fistula  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Oesophageal haemorrhage  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Oesophageal pain  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Oesophageal perforation  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Oesophagitis  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Pancreatitis  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Pancreatitis acute  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Peptic ulcer haemorrhage  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Rectal haemorrhage  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Small intestinal obstruction  1  0/627 (0.00%)  0 2/618 (0.32%)  2
Small intestinal perforation  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Stomatitis  1  14/627 (2.23%)  16 2/618 (0.32%)  2
Subileus  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Upper gastrointestinal haemorrhage  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Vomiting  1  6/627 (0.96%)  6 8/618 (1.29%)  10
General disorders     
Adverse drug reaction  1  1/627 (0.16%)  2 0/618 (0.00%)  0
Asthenia  1  3/627 (0.48%)  11 4/618 (0.65%)  4
Chest pain  1  1/627 (0.16%)  1 2/618 (0.32%)  2
Death  1  5/627 (0.80%)  5 3/618 (0.49%)  3
Disease progression  1  1/627 (0.16%)  1 2/618 (0.32%)  2
Fatigue  1  12/627 (1.91%)  18 6/618 (0.97%)  6
General physical health deterioration  1  5/627 (0.80%)  6 1/618 (0.16%)  1
Malaise  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Mucosal inflammation  1  2/627 (0.32%)  2 1/618 (0.16%)  1
Multi-organ failure  1  1/627 (0.16%)  1 1/618 (0.16%)  1
Non-cardiac chest pain  1  2/627 (0.32%)  2 3/618 (0.49%)  3
Oedema peripheral  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Pain  1  2/627 (0.32%)  2 2/618 (0.32%)  2
Peripheral swelling  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Pyrexia  1  10/627 (1.59%)  10 10/618 (1.62%)  10
Sudden death  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Hepatobiliary disorders     
Cholecystitis  1  1/627 (0.16%)  1 1/618 (0.16%)  1
Hepatic failure  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Hepatitis acute  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Jaundice  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Immune system disorders     
Anaphylactic shock  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Drug hypersensitivity  1  1/627 (0.16%)  2 2/618 (0.32%)  2
Infections and infestations     
Anal abscess  1  2/627 (0.32%)  4 0/618 (0.00%)  0
Appendicitis  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Appendicitis perforated  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Biliary tract infection  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Bronchitis  1  2/627 (0.32%)  2 6/618 (0.97%)  7
Bronchitis moraxella  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Bronchopneumonia  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Candida infection  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Catheter site infection  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Cellulitis  1  3/627 (0.48%)  4 0/618 (0.00%)  0
Cellulitis staphylococcal  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Clostridium difficile colitis  1  2/627 (0.32%)  2 1/618 (0.16%)  1
Device related infection  1  1/627 (0.16%)  1 2/618 (0.32%)  2
Device related sepsis  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Diverticulitis  1  3/627 (0.48%)  4 0/618 (0.00%)  0
Empyema  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Gastroenteritis  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Infection  1  2/627 (0.32%)  2 0/618 (0.00%)  0
Lobar pneumonia  1  7/627 (1.12%)  7 8/618 (1.29%)  8
Localised infection  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Lower respiratory tract infection  1  2/627 (0.32%)  2 1/618 (0.16%)  3
Lung infection  1  3/627 (0.48%)  6 5/618 (0.81%)  5
Neutropenic infection  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Neutropenic sepsis  1  2/627 (0.32%)  2 2/618 (0.32%)  2
Oral candidiasis  1  2/627 (0.32%)  2 0/618 (0.00%)  0
Oral herpes  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Osteomyelitis  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Paronychia  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Pelvic abscess  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Peritonitis  1  2/627 (0.32%)  2 0/618 (0.00%)  0
Pharyngitis  1  3/627 (0.48%)  3 0/618 (0.00%)  0
Pneumocystis jirovecii pneumonia  1  0/627 (0.00%)  0 3/618 (0.49%)  3
Pneumonia  1  37/627 (5.90%)  43 41/618 (6.63%)  48
Pneumonia bacterial  1  2/627 (0.32%)  2 0/618 (0.00%)  0
Pneumonia escherichia  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Pneumonia pneumococcal  1  0/627 (0.00%)  0 2/618 (0.32%)  2
Pneumonia staphylococcal  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Pneumonia streptococcal  1  1/627 (0.16%)  1 1/618 (0.16%)  1
Postoperative wound infection  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Respiratory tract infection  1  3/627 (0.48%)  3 3/618 (0.49%)  3
Sepsis  1  3/627 (0.48%)  3 2/618 (0.32%)  2
Septic shock  1  2/627 (0.32%)  3 3/618 (0.49%)  3
Staphylococcal sepsis  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Stenotrophomonas sepsis  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Upper respiratory tract infection  1  2/627 (0.32%)  2 4/618 (0.65%)  4
Urinary tract infection  1  1/627 (0.16%)  1 1/618 (0.16%)  1
Injury, poisoning and procedural complications     
Ankle fracture  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Fall  1  2/627 (0.32%)  2 2/618 (0.32%)  2
Femoral neck fracture  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Femur fracture  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Infusion related reaction  1  3/627 (0.48%)  3 0/618 (0.00%)  0
Pneumothorax traumatic  1  3/627 (0.48%)  3 1/618 (0.16%)  1
Pubis fracture  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Rib fracture  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Suture related complication  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Traumatic arthropathy  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Investigations     
Blood alkaline phosphatase increased  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Diagnostic aspiration  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Gamma-glutamyltransferase increased  1  0/627 (0.00%)  0 1/618 (0.16%)  1
International normalised ratio increased  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Liver function test abnormal  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Neutrophil count decreased  1  9/627 (1.44%)  10 3/618 (0.49%)  3
Platelet count decreased  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Transaminases increased  1  0/627 (0.00%)  0 1/618 (0.16%)  1
White blood cell count decreased  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Metabolism and nutrition disorders     
Cachexia  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Decreased appetite  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Dehydration  1  15/627 (2.39%)  17 15/618 (2.43%)  18
Failure to thrive  1  2/627 (0.32%)  2 0/618 (0.00%)  0
Hypercalcaemia  1  0/627 (0.00%)  0 2/618 (0.32%)  3
Hyperglycaemia  1  1/627 (0.16%)  1 2/618 (0.32%)  3
Hyperkalaemia  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Hypoglycaemia  1  1/627 (0.16%)  1 1/618 (0.16%)  1
Hyponatraemia  1  4/627 (0.64%)  4 3/618 (0.49%)  3
Hypovolaemia  1  3/627 (0.48%)  3 0/618 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Arthralgia  1  2/627 (0.32%)  2 1/618 (0.16%)  1
Arthritis  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Flank pain  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Muscular weakness  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Musculoskeletal chest pain  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Musculoskeletal pain  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Myalgia  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Osteonecrosis  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Pain in extremity  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Pathological fracture  1  1/627 (0.16%)  1 2/618 (0.32%)  2
Spinal disorder  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Intracranial tumour haemorrhage  1  2/627 (0.32%)  2 0/618 (0.00%)  0
Lymphangiosis carcinomatosa  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Malignant ascites  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Malignant pleural effusion  1  1/627 (0.16%)  1 5/618 (0.81%)  6
Metastases to bone  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Metastases to central nervous system  1  2/627 (0.32%)  2 3/618 (0.49%)  3
Metastases to liver  1  0/627 (0.00%)  0 2/618 (0.32%)  2
Metastases to meninges  1  2/627 (0.32%)  2 1/618 (0.16%)  1
Metastases to spine  1  2/627 (0.32%)  4 3/618 (0.49%)  3
Metastatic neoplasm  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Metastatic pain  1  5/627 (0.80%)  6 7/618 (1.13%)  10
Pericardial effusion malignant  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Small intestine carcinoma  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Tumour associated fever  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Tumour compression  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Tumour haemorrhage  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Tumour necrosis  1  1/627 (0.16%)  2 0/618 (0.00%)  0
Nervous system disorders     
Aphasia  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Brain oedema  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Cerebral haemorrhage  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Cerebral infarction  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Cerebral ischaemia  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Cerebrovascular accident  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Cognitive disorder  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Convulsion  1  3/627 (0.48%)  3 0/618 (0.00%)  0
Dizziness  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Headache  1  1/627 (0.16%)  2 2/618 (0.32%)  2
Hemiparesis  1  1/627 (0.16%)  2 0/618 (0.00%)  0
Hemiplegia  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Ischaemic stroke  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Ivth nerve paralysis  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Lethargy  1  1/627 (0.16%)  2 0/618 (0.00%)  0
Migraine with aura  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Neuralgia  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Paraparesis  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Peroneal nerve palsy  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Presyncope  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Radicular syndrome  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Senile dementia  1  1/627 (0.16%)  2 0/618 (0.00%)  0
Stupor  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Syncope  1  4/627 (0.64%)  4 4/618 (0.65%)  4
Toxic encephalopathy  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Tremor  1  1/627 (0.16%)  2 0/618 (0.00%)  0
Vocal cord paresis  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Psychiatric disorders     
Anxiety  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Confusional state  1  7/627 (1.12%)  7 1/618 (0.16%)  1
Conversion disorder  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Delirium  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Depression  1  1/627 (0.16%)  1 1/618 (0.16%)  2
Echolalia  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Mania  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Mental status changes  1  1/627 (0.16%)  1 1/618 (0.16%)  1
Renal and urinary disorders     
Acute prerenal failure  1  0/627 (0.00%)  0 1/618 (0.16%)  2
Haematuria  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Renal failure  1  1/627 (0.16%)  1 1/618 (0.16%)  1
Renal failure acute  1  4/627 (0.64%)  8 2/618 (0.32%)  2
Urinary retention  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Respiratory, thoracic and mediastinal disorders     
Acute respiratory distress syndrome  1  2/627 (0.32%)  2 2/618 (0.32%)  2
Acute respiratory failure  1  1/627 (0.16%)  1 6/618 (0.97%)  6
Aspiration  1  2/627 (0.32%)  2 0/618 (0.00%)  0
Atelectasis  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Bronchospasm  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Catarrh  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Chronic obstructive pulmonary disease  1  5/627 (0.80%)  7 4/618 (0.65%)  6
Cough  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Dyspnoea  1  11/627 (1.75%)  12 26/618 (4.21%)  32
Epistaxis  1  1/627 (0.16%)  2 1/618 (0.16%)  1
Haemoptysis  1  7/627 (1.12%)  9 6/618 (0.97%)  7
Haemothorax  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Hiccups  1  1/627 (0.16%)  2 1/618 (0.16%)  1
Hydrothorax  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Hypoxia  1  1/627 (0.16%)  1 1/618 (0.16%)  1
Interstitial lung disease  1  0/627 (0.00%)  0 3/618 (0.49%)  3
Lung infiltration  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Oropharyngeal pain  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Pleural effusion  1  9/627 (1.44%)  10 21/618 (3.40%)  23
Pneumomediastinum  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Pneumonia aspiration  1  1/627 (0.16%)  1 1/618 (0.16%)  2
Pneumonitis  1  2/627 (0.32%)  2 3/618 (0.49%)  3
Pneumothorax  1  5/627 (0.80%)  5 3/618 (0.49%)  3
Pneumothorax spontaneous  1  2/627 (0.32%)  2 2/618 (0.32%)  2
Pulmonary bulla  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Pulmonary congestion  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Pulmonary embolism  1  8/627 (1.28%)  8 12/618 (1.94%)  13
Pulmonary haemorrhage  1  4/627 (0.64%)  4 4/618 (0.65%)  5
Pulmonary oedema  1  1/627 (0.16%)  1 1/618 (0.16%)  1
Respiratory acidosis  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Respiratory arrest  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Respiratory disorder  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Respiratory distress  1  0/627 (0.00%)  0 2/618 (0.32%)  2
Respiratory failure  1  3/627 (0.48%)  3 9/618 (1.46%)  10
Respiratory tract haemorrhage  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Tachypnoea  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Skin and subcutaneous tissue disorders     
Hyperhidrosis  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Pruritus  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Psoriasis  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Rash  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Subcutaneous emphysema  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Urticaria  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Surgical and medical procedures     
Hospitalisation  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Lung lobectomy  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Vascular disorders     
Aortic aneurysm rupture  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Deep vein thrombosis  1  2/627 (0.32%)  3 2/618 (0.32%)  2
Hypertension  1  1/627 (0.16%)  1 1/618 (0.16%)  1
Hypotension  1  3/627 (0.48%)  3 4/618 (0.65%)  5
Iliac artery occlusion  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Jugular vein thrombosis  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Orthostatic hypotension  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Peripheral arterial occlusive disease  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Peripheral artery aneurysm  1  1/627 (0.16%)  1 0/618 (0.00%)  0
Superior vena cava syndrome  1  0/627 (0.00%)  0 1/618 (0.16%)  1
Venous thrombosis limb  1  0/627 (0.00%)  0 1/618 (0.16%)  1
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 and Docetaxel Placebo and Docetaxel
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   601/627 (95.85%)      583/618 (94.34%)    
Blood and lymphatic system disorders     
Anaemia  1  135/627 (21.53%)  306 174/618 (28.16%)  399
Leukopenia  1  79/627 (12.60%)  259 68/618 (11.00%)  151
Neutropenia  1  228/627 (36.36%)  547 188/618 (30.42%)  415
Thrombocytopenia  1  51/627 (8.13%)  114 27/618 (4.37%)  48
Eye disorders     
Lacrimation increased  1  85/627 (13.56%)  100 29/618 (4.69%)  31
Gastrointestinal disorders     
Abdominal pain  1  56/627 (8.93%)  69 35/618 (5.66%)  41
Constipation  1  107/627 (17.07%)  135 110/618 (17.80%)  132
Diarrhoea  1  200/627 (31.90%)  338 175/618 (28.32%)  226
Dyspepsia  1  37/627 (5.90%)  47 18/618 (2.91%)  25
Nausea  1  170/627 (27.11%)  236 173/618 (27.99%)  256
Stomatitis  1  143/627 (22.81%)  245 81/618 (13.11%)  104
Vomiting  1  88/627 (14.04%)  117 86/618 (13.92%)  119
General disorders     
Asthenia  1  72/627 (11.48%)  178 65/618 (10.52%)  127
Fatigue  1  287/627 (45.77%)  623 260/618 (42.07%)  524
Mucosal inflammation  1  103/627 (16.43%)  167 43/618 (6.96%)  53
Oedema peripheral  1  107/627 (17.07%)  149 55/618 (8.90%)  86
Pain  1  35/627 (5.58%)  40 33/618 (5.34%)  37
Pyrexia  1  100/627 (15.95%)  148 79/618 (12.78%)  114
Investigations     
Neutrophil count decreased  1  112/627 (17.86%)  281 89/618 (14.40%)  193
Platelet count decreased  1  36/627 (5.74%)  104 9/618 (1.46%)  20
Weight decreased  1  67/627 (10.69%)  84 49/618 (7.93%)  56
White blood cell count decreased  1  58/627 (9.25%)  148 50/618 (8.09%)  219
Metabolism and nutrition disorders     
Decreased appetite  1  189/627 (30.14%)  290 163/618 (26.38%)  221
Dehydration  1  39/627 (6.22%)  47 24/618 (3.88%)  31
Hyperglycaemia  1  39/627 (6.22%)  83 25/618 (4.05%)  49
Musculoskeletal and connective tissue disorders     
Arthralgia  1  71/627 (11.32%)  110 51/618 (8.25%)  86
Back pain  1  73/627 (11.64%)  113 56/618 (9.06%)  83
Bone pain  1  31/627 (4.94%)  40 36/618 (5.83%)  57
Myalgia  1  79/627 (12.60%)  123 65/618 (10.52%)  110
Pain in extremity  1  50/627 (7.97%)  60 26/618 (4.21%)  31
Nervous system disorders     
Dizziness  1  43/627 (6.86%)  54 46/618 (7.44%)  52
Dysgeusia  1  69/627 (11.00%)  83 46/618 (7.44%)  55
Headache  1  66/627 (10.53%)  88 65/618 (10.52%)  78
Paraesthesia  1  38/627 (6.06%)  49 36/618 (5.83%)  46
Peripheral sensory neuropathy  1  74/627 (11.80%)  121 60/618 (9.71%)  102
Psychiatric disorders     
Insomnia  1  69/627 (11.00%)  78 54/618 (8.74%)  55
Respiratory, thoracic and mediastinal disorders     
Cough  1  137/627 (21.85%)  194 131/618 (21.20%)  169
Dysphonia  1  38/627 (6.06%)  49 23/618 (3.72%)  23
Dyspnoea  1  150/627 (23.92%)  220 148/618 (23.95%)  207
Epistaxis  1  116/627 (18.50%)  149 41/618 (6.63%)  45
Haemoptysis  1  36/627 (5.74%)  38 31/618 (5.02%)  37
Oropharyngeal pain  1  49/627 (7.81%)  65 30/618 (4.85%)  39
Productive cough  1  40/627 (6.38%)  61 34/618 (5.50%)  41
Skin and subcutaneous tissue disorders     
Alopecia  1  163/627 (26.00%)  192 156/618 (25.24%)  176
Nail discolouration  1  41/627 (6.54%)  45 27/618 (4.37%)  27
Rash  1  44/627 (7.02%)  56 36/618 (5.83%)  51
Vascular disorders     
Hypertension  1  67/627 (10.69%)  129 29/618 (4.69%)  107
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.1
Three participants randomized to placebo and docetaxel received 1 dose of ramucirumab in error. They are included in the placebo and docetaxel arm in the ITT population and are included in the ramucirumab and docetaxel arm in the Safety population.
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: NCT01168973    
Other Study ID Numbers: 13852
I4T-MC-JVBA ( Other Identifier: Eli Lilly and Company )
2010-021297-11 ( EudraCT Number )
CP12-1027 ( Other Identifier: ImClone Trial Number )
CTRI/2011/08/001942 ( Registry Identifier: Clinical Trials Registry India )
First Submitted: July 16, 2010
First Posted: July 23, 2010
Results First Submitted: December 17, 2014
Results First Posted: December 29, 2014
Last Update Posted: September 25, 2019