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A Study of Ramucirumab (LY3009806) Plus Docetaxel in Participants With Urothelial Cancer (RANGE)

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02426125
Recruitment Status : Active, not recruiting
First Posted : April 24, 2015
Results First Posted : March 8, 2019
Last Update Posted : July 14, 2020
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 Urothelial Carcinoma
Interventions Drug: Ramucirumab
Drug: Docetaxel
Drug: Placebo
Enrollment 530
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.
Arm/Group Title Ramucirumab + Docetaxel Placebo + Docetaxel
Hide Arm/Group Description Ramucirumab (10 milligram/kilogram [mg/kg]) intravenously (IV) plus docetaxel (75 milligram/square meter [mg/m²]) IV in 21 day cycles. Participants may continue to receive treatment until discontinuation criteria are met. Placebo IV plus docetaxel (75 mg/m²) IV in 21 day cycles. Participants may continue to receive treatment until discontinuation criteria are met.
Period Title: Overall Study
Started 263 267
Received at Least One Dose of Study Drug 258 265
First Randomized Participants 216 221
Completed 234 241
Not Completed 29 26
Reason Not Completed
Lost to Follow-up             12             10
Protocol Violation             1             0
Withdrawal by Subject             16             16
Arm/Group Title Ramucirumab + Docetaxel Placebo + Docetaxel Total
Hide Arm/Group Description Ramucirumab (10 mg/kg) IV plus docetaxel (75 mg/m²) IV in 21 day cycles. Participants may continue to receive treatment until discontinuation criteria are met. Placebo IV plus docetaxel (75 mg/m²) IV in 21 day cycles. Participants may continue to receive treatment until discontinuation criteria are met. Total of all reporting groups
Overall Number of Baseline Participants 263 267 530
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 263 participants 267 participants 530 participants
64.6  (9.9) 64.8  (9.2) 64.7  (9.6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 263 participants 267 participants 530 participants
Female 50 52 102
Male 213 215 428
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 263 participants 267 participants 530 participants
Hispanic or Latino 13 10 23
Not Hispanic or Latino 208 219 427
Unknown or Not Reported 42 38 80
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 263 participants 267 participants 530 participants
American Indian or Alaska Native 1 0 1
Asian 54 61 115
Native Hawaiian or Other Pacific Islander 0 0 0
Black or African American 2 2 4
White 204 204 408
More than one race 0 0 0
Unknown or Not Reported 2 0 2
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 263 participants 267 participants 530 participants
Romania 5 5 10
Hungary 5 8 13
United States 17 18 35
Japan 24 30 54
Ukraine 5 3 8
United Kingdom 18 24 42
Russia 18 12 30
Spain 22 15 37
Greece 13 13 26
Canada 4 5 9
South Korea 16 9 25
Netherlands 17 18 35
Turkey 11 17 28
Belgium 6 1 7
Taiwan 13 18 31
Denmark 5 6 11
Poland 4 4 8
Italy 23 14 37
Mexico 3 1 4
Israel 7 11 18
Australia 6 6 12
France 16 18 34
Germany 5 11 16
1.Primary Outcome
Title Progression Free Survival (PFS)
Hide Description PFS defined as time from first day of therapy to first evidence of disease progression defined by Response Evaluation Criteria in Solid Tumors (RECIST v1.1) or death from any cause. Progressive Disease (PD) is at least 20% increase in sum of diameters of target lesions, with reference being the smallest sum on study and plus absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. If participant does not have complete baseline disease assessment, then PFS time was censored at date of first dose, regardless of whether or not objectively determined disease progression or death has been observed for participant. If participant is not known to have died or have objective progression as of data inclusion cutoff date for analysis, PFS time was censored at last adequate tumor assessment date.
Time Frame Randomization to Radiological Disease Progression or Death from Any Cause (Up to 18 Months)
Hide Outcome Measure Data
Hide Analysis Population Description
The first randomized participants. Censored participants: Ramucirumab + Docetaxel = 58, Placebo + Docetaxel =38.
Arm/Group Title Ramucirumab + Docetaxel Placebo + Docetaxel
Hide Arm/Group Description:
Ramucirumab (10 mg/kg) IV plus docetaxel (75 mg/m²) IV in 21 day cycles. Participants may continue to receive treatment until discontinuation criteria are met.
Placebo IV plus docetaxel (75 mg/m²) IV in 21 day cycles. Participants may continue to receive treatment until discontinuation criteria are met.
Overall Number of Participants Analyzed 216 221
Median (95% Confidence Interval)
Unit of Measure: Months
4.07
(2.96 to 4.47)
2.76
(2.60 to 2.96)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ramucirumab + Docetaxel, Placebo + Docetaxel
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0118
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.757
Confidence Interval (2-Sided) 95%
0.607 to 0.943
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Overall Survival (OS)
Hide Description OS is the time from the date of randomization to the date of death from any cause. For each participant who is not known to have died as of the data inclusion cutoff date for a particular analysis, OS was censored for that analysis at the last known alive date prior to the data inclusion cutoff date.
Time Frame Randomization to Date of Death from Any Cause (Up to 21 Months)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants. Censored participants: Ramucirumab + Docetaxel = 78, Placebo + Docetaxel = 67.
Arm/Group Title Ramucirumab + Docetaxel Placebo + Docetaxel
Hide Arm/Group Description:
Ramucirumab (10 mg/kg) IV plus docetaxel IV in 21 day cycles. Participants may continue to receive treatment until discontinuation criteria are met.
Placebo IV plus docetaxel (75 mg/m²) IV in 21 day cycles. Participants may continue to receive treatment until discontinuation criteria are met.
Overall Number of Participants Analyzed 263 267
Median (95% Confidence Interval)
Unit of Measure: Months
9.40
(7.89 to 11.43)
7.85
(7.00 to 9.30)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ramucirumab + Docetaxel, Placebo + Docetaxel
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2461
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.887
Confidence Interval (2-Sided) 95%
0.724 to 1.086
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Participants With an 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 normalization 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 Randomization to Disease Progression (Up to 18 Months)
Hide Outcome Measure Data
Hide Analysis Population Description
The first randomized participants.
Arm/Group Title Ramucirumab + Docetaxel Placebo + Docetaxel
Hide Arm/Group Description:
Ramucirumab (10 mg/kg) IV plus docetaxel (75 mg/m²) IV in 21 day cycles. Participants may continue to receive treatment until discontinuation criteria are met.
Placebo IV plus docetaxel (75 mg/m²) IV in 21 day cycles. Participants may continue to receive treatment until discontinuation criteria are met.
Overall Number of Participants Analyzed 216 221
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
24.5
(18.8 to 30.3)
14.0
(9.4 to 18.6)
4.Secondary Outcome
Title Percentage of Participants With Disease Control Rate (DCR)
Hide Description DCR is the percentage of participants with a best overall response of CR, PR, or Stable Disease (SD) as per Response using RECIST v1.1. Target lesions - CR: Disappearance of all lesions; any pathological lymph nodes must have reduction in short axis to <10 mm. PR: At least a 30% decrease in the sum of diameters of lesions vs the baseline sum. Progressive Disease (PD): At least a 20% increase in the sum of diameters of lesions vs the smallest sum on study (the sum must also demonstrate an absolute increase of at least 5 mm); or the appearance of new lesion(s). SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Non target lesions - CR: Disappearance of all lesions and normalization of tumor marker levels; all lymph nodes must be non-pathological in size. Non-CR/Non-PD: Persistence of lesion(s) and/or maintenance of abnormal tumor marker levels. PD: Unequivocal progression of existing lesions or the appearance of new lesion(s).
Time Frame Randomization to Disease Progression (Up to 18 Months)
Hide Outcome Measure Data
Hide Analysis Population Description
The first randomized participants.
Arm/Group Title Ramucirumab + Docetaxel Placebo + Docetaxel
Hide Arm/Group Description:
Ramucirumab (10 mg/kg) IV plus docetaxel (75 mg/m²) IV in 21 day cycles. Participants may continue to receive treatment until discontinuation criteria are met.
Placebo IV plus docetaxel (75 mg/m²) IV in 21 day cycles. Participants may continue to receive treatment until discontinuation criteria are met.
Overall Number of Participants Analyzed 216 221
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
63.4
(57.0 to 69.8)
56.1
(49.6 to 62.7)
5.Secondary Outcome
Title Duration of Response (DoR)
Hide Description Objective response was achieved if they had a best overall response of CR or PR. Target lesions- CR: Disappearance of all lesions; any pathological lymph nodes have reduction in short axis to <10 mm. PR: At least a 30% decrease in the sum of diameters of lesions vs the baseline sum. PD: At least a 20% increase in the sum of diameters of lesions vs the smallest sum on study(the sum must also demonstrate an absolute increase of at least 5 mm); or the appearance of new lesion(s). Non target lesions - CR: Disappearance of all lesions and normalization of tumour marker levels; all lymph nodes must be non-pathological in size. Non-CR/Non-PD: Persistence of lesion(s) and/or maintenance of abnormal tumor marker levels. PD: Unequivocal progression of existing lesions or the appearance of new lesion(s). If a participant was not known to have died or have radiographically documented PD as of the data inclusion cutoff date, DOR was censored at the date of the last adequate tumor assessment.
Time Frame Date of Complete Response (CR) or Partial Response (PR) to Date of Objective Disease Progression or Death Due to Any Cause (Up to 18 Months)
Hide Outcome Measure Data
Hide Analysis Population Description
The first randomized participants with CR or PR. Participants censored in Ramucirumab + Docetaxel = 21 and in Placebo + Docetaxel = 9.
Arm/Group Title Ramucirumab + Docetaxel Placebo + Docetaxel
Hide Arm/Group Description:
Ramucirumab (10 mg/kg) IV plus docetaxel (75 mg/m²) IV in 21 day cycles. Participants may continue to receive treatment until discontinuation criteria are met.
Placebo IV plus docetaxel (75 mg/m²) IV in 21 day cycles. Participants may continue to receive treatment until discontinuation criteria are met.
Overall Number of Participants Analyzed 53 31
Median (95% Confidence Interval)
Unit of Measure: Months
5.65
(3.94 to 7.06)
4.17
(2.86 to 5.52)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ramucirumab + Docetaxel, Placebo + Docetaxel
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.652
Confidence Interval (2-Sided) 95%
0.376 to 1.131
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Time to Deterioration in Quality of Life (QoL) on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) - Global Health Status/ QoL Scale
Hide Description Time to sustained deterioration was defined as time from randomization to first worsening in QoL with no subsequent non-worsened assessment. Worsening in global health status/QoL was defined as a decrease of ≥10 points on a 100-point scale. If a participant did not report worsening, time to sustained deterioration was censored at date of last non-worsened assessment. Scores for global health status/QoL range from 0 to 100 with; higher scores representing better QoL.
Time Frame Randomization, 30 Days After Treatment Discontinuation (Up to 18 Months)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants. Censored participants: Ramucirumab + Docetaxel = 167, Placebo + Docetaxel = 170.
Arm/Group Title Ramucirumab + Docetaxel Placebo + Docetaxel
Hide Arm/Group Description:
Ramucirumab (10 mg/kg) IV plus docetaxel (75 mg/m²) IV in 21 day cycles. Participants may continue to receive treatment until discontinuation criteria are met.
Placebo IV plus docetaxel (75 mg/m²) IV in 21 day cycles. Participants may continue to receive treatment until discontinuation criteria are met.
Overall Number of Participants Analyzed 263 267
Median (95% Confidence Interval)
Unit of Measure: Months
6.47
(4.17 to 8.31)
4.34
(3.48 to 5.52)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ramucirumab + Docetaxel, Placebo + Docetaxel
Comments Global health status/QoL
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.610
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.931
Confidence Interval (2-Sided) 95%
0.701 to 1.235
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Change From Baseline on the EuroQol 5-Dimension, 5-Level Questionnaire (EQ-5D-5L) Index Score
Hide Description The EQ-5D-5L is a standardized instrument for use as a measure of self-reported health status. Participants completed the 5-level (no problem, slight problem, moderate problem, severe problem, and inability or extreme problem), 5-dimension (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) questionnaire concerning their current health state. A unique EQ-5D health state is defined by combining 1 level from each of the 5 dimensions. Scores range from 0 (death) to 1 (perfect health), but scores <0 are possible based on the algorithm.
Time Frame Randomization, 30 Days After Treatment Discontinuation (Up to 18 Months)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with baseline and 30-day follow-up data.
Arm/Group Title Ramucirumab + Docetaxel Placebo + Docetaxel
Hide Arm/Group Description:
Ramucirumab (10 mg/kg) IV plus docetaxel IV in 21 day cycles. Participants may continue to receive treatment until discontinuation criteria are met.
Placebo IV plus docetaxel (75 mg/m²) IV in 21 day cycles. Participants may continue to receive treatment until discontinuation criteria are met.
Overall Number of Participants Analyzed 83 102
Mean (Standard Deviation)
Unit of Measure: units on a scale
-0.10  (0.26) -0.19  (0.26)
8.Secondary Outcome
Title Change From Baseline on the EuroQol 5-Dimension, 5-Level Questionnaire (EQ-5D-5L) Visual Analogue Scale (VAS)
Hide Description The EQ-5D-5L is a standardized instrument for use as a measure of self-reported health status. A unique EQ-5D health state is defined by combining 1 level from each of the 5 dimensions. Participants indicated their current health status by marking on a visual analogue scale (VAS) ranging from 100 (best imaginable health state) to 0 (worst imaginable health state).
Time Frame Randomization, 30 Days After Treatment Discontinuation (Up to 18 Months)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with baseline and 30-day follow-up data.
Arm/Group Title Ramucirumab + Docetaxel Placebo + Docetaxel
Hide Arm/Group Description:
Ramucirumab (10 mg/kg) IV plus docetaxel (75 mg/m²) IV in 21 day cycles. Participants may continue to receive treatment until discontinuation criteria are met.
Placebo IV plus docetaxel (75 mg/m²) IV in 21 day cycles. Participants may continue to receive treatment until discontinuation criteria are met.
Overall Number of Participants Analyzed 86 105
Mean (Standard Deviation)
Unit of Measure: millimeter (mm)
-7.87  (17.95) -10.91  (16.77)
9.Secondary Outcome
Title Pharmacokinetics (PK): Maximum Concentration (Cmax) of Ramucirumab
Hide Description Maximum concentration (Cmax) of Ramucirumab at the end of ramucirumab infusion
Time Frame Cycle 1 and Cycle 9, Day 1: Predose, Postdose
Hide Outcome Measure Data
Hide Analysis Population Description
The first randomized participants who had evaluable PK data.
Arm/Group Title Ramucirumab + Docetaxel
Hide Arm/Group Description:
Ramucirumab IV plus docetaxel (75 mg/m²) IV in 21 day cycles. Participants may continue to receive treatment until discontinuation criteria are met.
Overall Number of Participants Analyzed 216
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: microgram/milliliter (μg/mL)
Cycle 1
199
(28%)
Cycle 9
266
(29%)
10.Secondary Outcome
Title PK: Minimum Concentration (Cmin) of Ramucirumab
Hide Description Minimum concentration (Cmin) of Ramucirumab following administration every 3 weeks.
Time Frame Day 1 of Cycle 2, 3, 5 and 9 (Predose and Postdose)
Hide Outcome Measure Data
Hide Analysis Population Description
The first randomized participants who had evaluable PK data.
Arm/Group Title Ramucirumab + Docetaxel
Hide Arm/Group Description:
Ramucirumab (10 mg/kg) IV plus docetaxel (75 mg/m²) IV in 21 day cycles. Participants may continue to receive treatment until discontinuation criteria are met.
Overall Number of Participants Analyzed 216
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: μg/mL
Cycle 2 Number Analyzed 179 participants
15.0
(64%)
Cycle 3 Number Analyzed 139 participants
23.0
(63%)
Cycle 5 Number Analyzed 82 participants
33.9
(59%)
Cycle 9 Number Analyzed 15 participants
49.7
(55%)
11.Secondary Outcome
Title Number of Participants With Anti-Ramucirumab Antibodies
Hide Description Number of participants with positive treatment emergent anti-ramucirumab antibodies was summarized by treatment group.
Time Frame 18 Months
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study drug at baseline and post-baseline.
Arm/Group Title Ramucirumab + Docetaxel Placebo + Docetaxel
Hide Arm/Group Description:
Ramucirumab (10 mg/kg) IV plus docetaxel (75 mg/m²) IV in 21 day cycles. Participants may continue to receive treatment until discontinuation criteria are met.
Placebo IV plus docetaxel (75 mg/m²) IV in 21 day cycles. Participants may continue to receive treatment until discontinuation criteria are met.
Overall Number of Participants Analyzed 258 265
Measure Type: Count of Participants
Unit of Measure: Participants
22 24
Time Frame Up to 18 Months
Adverse Event Reporting Description All randomized participants who received at least one dose of study drug.
 
Arm/Group Title Ramucirumab + Docetaxel Placebo + Docetaxel
Hide Arm/Group Description Ramucirumab (10 mg/kg) IV plus docetaxel (75 mg/m²) IV in 21 day cycles. Participants may continue to receive treatment until discontinuation criteria are met. Placebo IV plus docetaxel (75 mg/m²) IV in 21 day cycles. Participants may continue to receive treatment until discontinuation criteria are met.
All-Cause Mortality
Ramucirumab + Docetaxel Placebo + Docetaxel
Affected / at Risk (%) Affected / at Risk (%)
Total   100/258 (38.76%)      119/265 (44.91%)    
Hide Serious Adverse Events
Ramucirumab + Docetaxel Placebo + Docetaxel
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   100/258 (38.76%)      104/265 (39.25%)    
Blood and lymphatic system disorders     
Anaemia  1  0/258 (0.00%)  0 4/265 (1.51%)  4
Febrile neutropenia  1  17/258 (6.59%)  20 12/265 (4.53%)  13
Haemorrhagic anaemia  1  1/258 (0.39%)  1 0/265 (0.00%)  0
Leukopenia  1  0/258 (0.00%)  0 2/265 (0.75%)  3
Neutropenia  1  4/258 (1.55%)  5 2/265 (0.75%)  2
Cardiac disorders     
Arteriospasm coronary  1  1/258 (0.39%)  1 0/265 (0.00%)  0
Cardiac arrest  1  1/258 (0.39%)  1 0/265 (0.00%)  0
Cardiac failure  1  1/258 (0.39%)  1 0/265 (0.00%)  0
Cardiac failure congestive  1  1/258 (0.39%)  1 1/265 (0.38%)  1
Intracardiac thrombus  1  0/258 (0.00%)  0 1/265 (0.38%)  1
Myocardial infarction  1  2/258 (0.78%)  2 0/265 (0.00%)  0
Pericardial effusion  1  0/258 (0.00%)  0 1/265 (0.38%)  1
Supraventricular tachycardia  1  1/258 (0.39%)  1 0/265 (0.00%)  0
Ear and labyrinth disorders     
Vertigo  1  0/258 (0.00%)  0 1/265 (0.38%)  1
Gastrointestinal disorders     
Abdominal pain  1  0/258 (0.00%)  0 2/265 (0.75%)  2
Anal fistula  1  1/258 (0.39%)  1 1/265 (0.38%)  1
Colitis  1  1/258 (0.39%)  1 0/265 (0.00%)  0
Constipation  1  0/258 (0.00%)  0 1/265 (0.38%)  1
Diarrhoea  1  6/258 (2.33%)  6 4/265 (1.51%)  5
Enterocolitis  1  0/258 (0.00%)  0 1/265 (0.38%)  1
Enterovesical fistula  1  1/258 (0.39%)  1 0/265 (0.00%)  0
Gastric haemorrhage  1  1/258 (0.39%)  1 0/265 (0.00%)  0
Gastrointestinal haemorrhage  1  2/258 (0.78%)  2 1/265 (0.38%)  1
Gastrointestinal ulcer  1  1/258 (0.39%)  1 0/265 (0.00%)  0
Haemorrhoids  1  1/258 (0.39%)  1 0/265 (0.00%)  0
Ileal perforation  1  1/258 (0.39%)  1 0/265 (0.00%)  0
Intestinal ischaemia  1  1/258 (0.39%)  1 0/265 (0.00%)  0
Intestinal obstruction  1  1/258 (0.39%)  1 2/265 (0.75%)  2
Intestinal perforation  1  0/258 (0.00%)  0 1/265 (0.38%)  1
Large intestine perforation  1  1/258 (0.39%)  1 0/265 (0.00%)  0
Nausea  1  2/258 (0.78%)  2 2/265 (0.75%)  2
Oesophagitis  1  1/258 (0.39%)  1 0/265 (0.00%)  0
Rectal haemorrhage  1  0/258 (0.00%)  0 1/265 (0.38%)  1
Small intestinal obstruction  1  0/258 (0.00%)  0 1/265 (0.38%)  1
Small intestinal perforation  1  1/258 (0.39%)  1 0/265 (0.00%)  0
Stomatitis  1  0/258 (0.00%)  0 1/265 (0.38%)  1
Tooth disorder  1  0/258 (0.00%)  0 1/265 (0.38%)  1
Upper gastrointestinal haemorrhage  1  0/258 (0.00%)  0 1/265 (0.38%)  1
Vomiting  1  3/258 (1.16%)  3 2/265 (0.75%)  2
General disorders     
Asthenia  1  0/258 (0.00%)  0 2/265 (0.75%)  2
Chest pain  1  0/258 (0.00%)  0 1/265 (0.38%)  1
Death  1  1/258 (0.39%)  1 2/265 (0.75%)  2
Fatigue  1  5/258 (1.94%)  5 2/265 (0.75%)  2
General physical health deterioration  1  1/258 (0.39%)  1 0/265 (0.00%)  0
Generalised oedema  1  0/258 (0.00%)  0 1/265 (0.38%)  1
Malaise  1  1/258 (0.39%)  1 1/265 (0.38%)  1
Mucosal inflammation  1  1/258 (0.39%)  1 1/265 (0.38%)  1
Non-cardiac chest pain  1  2/258 (0.78%)  2 0/265 (0.00%)  0
Pain  1  0/258 (0.00%)  0 2/265 (0.75%)  2
Pyrexia  1  3/258 (1.16%)  3 8/265 (3.02%)  9
Sudden death  1  0/258 (0.00%)  0 1/265 (0.38%)  1
Hepatobiliary disorders     
Cholelithiasis  1  1/258 (0.39%)  1 0/265 (0.00%)  0
Infections and infestations     
Abdominal abscess  1  1/258 (0.39%)  1 0/265 (0.00%)  0
Appendicitis  1  1/258 (0.39%)  1 0/265 (0.00%)  0
Bacteraemia  1  0/258 (0.00%)  0 1/265 (0.38%)  1
Bronchitis  1  0/258 (0.00%)  0 1/265 (0.38%)  1
Cellulitis  1  0/258 (0.00%)  0 1/265 (0.38%)  1
Clostridium difficile colitis  1  1/258 (0.39%)  1 0/265 (0.00%)  0
Cystitis  1  1/258 (0.39%)  1 1/265 (0.38%)  1
Device related infection  1  2/258 (0.78%)  2 0/265 (0.00%)  0
Diverticulitis  1  0/258 (0.00%)  0 1/265 (0.38%)  1
Gastroenteritis  1  0/258 (0.00%)  0 1/265 (0.38%)  1
Gingivitis  1  0/258 (0.00%)  0 1/265 (0.38%)  1
Infection  1  1/258 (0.39%)  1 1/265 (0.38%)  1
Kidney infection  1  0/258 (0.00%)  0 1/265 (0.38%)  1
Lower respiratory tract infection  1  1/258 (0.39%)  1 0/265 (0.00%)  0
Lung infection  1  1/258 (0.39%)  1 3/265 (1.13%)  3
Neutropenic sepsis  1  1/258 (0.39%)  1 0/265 (0.00%)  0
Pneumonia  1  4/258 (1.55%)  4 5/265 (1.89%)  5
Pyelonephritis  1  2/258 (0.78%)  2 2/265 (0.75%)  2
Respiratory tract infection  1  1/258 (0.39%)  2 0/265 (0.00%)  0
Sepsis  1  6/258 (2.33%)  6 3/265 (1.13%)  3
Stoma site abscess  1  1/258 (0.39%)  1 0/265 (0.00%)  0
Toxic shock syndrome  1  0/258 (0.00%)  0 1/265 (0.38%)  1
Urinary tract infection  1  10/258 (3.88%)  10 10/265 (3.77%)  14
Urosepsis  1  2/258 (0.78%)  2 5/265 (1.89%)  5
Injury, poisoning and procedural complications     
Fall  1  1/258 (0.39%)  1 1/265 (0.38%)  1
Infusion related reaction  1  2/258 (0.78%)  2 1/265 (0.38%)  1
Lower limb fracture  1  0/258 (0.00%)  0 1/265 (0.38%)  1
Subarachnoid haemorrhage  1  0/258 (0.00%)  0 1/265 (0.38%)  1
Urostomy complication  1  0/258 (0.00%)  0 1/265 (0.38%)  2
Investigations     
Blood creatinine increased  1  1/258 (0.39%)  1 2/265 (0.75%)  2
Neutrophil count decreased  1  2/258 (0.78%)  3 2/265 (0.75%)  3
Platelet count decreased  1  1/258 (0.39%)  1 1/265 (0.38%)  1
Metabolism and nutrition disorders     
Decreased appetite  1  0/258 (0.00%)  0 1/265 (0.38%)  2
Dehydration  1  1/258 (0.39%)  1 0/265 (0.00%)  0
Diabetic metabolic decompensation  1  0/258 (0.00%)  0 1/265 (0.38%)  1
Hyperglycaemia  1  1/258 (0.39%)  1 1/265 (0.38%)  1
Hyperkalaemia  1  2/258 (0.78%)  2 1/265 (0.38%)  1
Hyponatraemia  1  3/258 (1.16%)  3 0/265 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Back pain  1  0/258 (0.00%)  0 2/265 (0.75%)  2
Fistula  1  0/258 (0.00%)  0 1/265 (0.38%)  1
Muscular weakness  1  0/258 (0.00%)  0 1/265 (0.38%)  1
Myalgia  1  1/258 (0.39%)  1 0/265 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Tumour haemorrhage  1  0/258 (0.00%)  0 1/265 (0.38%)  1
Nervous system disorders     
Basilar artery thrombosis  1  1/258 (0.39%)  1 0/265 (0.00%)  0
Cerebral ischaemia  1  1/258 (0.39%)  1 0/265 (0.00%)  0
Cerebrovascular accident  1  0/258 (0.00%)  0 1/265 (0.38%)  1
Dizziness  1  1/258 (0.39%)  1 0/265 (0.00%)  0
Headache  1  1/258 (0.39%)  1 0/265 (0.00%)  0
Presyncope  1  0/258 (0.00%)  0 1/265 (0.38%)  1
Syncope  1  1/258 (0.39%)  1 2/265 (0.75%)  2
Transient ischaemic attack  1  0/258 (0.00%)  0 1/265 (0.38%)  1
Product Issues     
Device connection issue  1  1/258 (0.39%)  1 0/265 (0.00%)  0
Psychiatric disorders     
Delirium  1  0/258 (0.00%)  0 2/265 (0.75%)  2
Mental status changes  1  1/258 (0.39%)  1 0/265 (0.00%)  0
Renal and urinary disorders     
Acute kidney injury  1  3/258 (1.16%)  3 0/265 (0.00%)  0
Haematuria  1  4/258 (1.55%)  4 6/265 (2.26%)  6
Hydronephrosis  1  0/258 (0.00%)  0 1/265 (0.38%)  1
Renal failure  1  3/258 (1.16%)  3 0/265 (0.00%)  0
Ureteric stenosis  1  0/258 (0.00%)  0 1/265 (0.38%)  1
Urinary tract obstruction  1  2/258 (0.78%)  2 1/265 (0.38%)  1
Respiratory, thoracic and mediastinal disorders     
Chronic obstructive pulmonary disease  1  0/258 (0.00%)  0 1/265 (0.38%)  1
Dyspnoea  1  4/258 (1.55%)  5 3/265 (1.13%)  3
Epistaxis  1  1/258 (0.39%)  1 0/265 (0.00%)  0
Hiccups  1  0/258 (0.00%)  0 1/265 (0.38%)  1
Laryngeal inflammation  1  0/258 (0.00%)  0 1/265 (0.38%)  1
Obstructive airways disorder  1  0/258 (0.00%)  0 1/265 (0.38%)  1
Pleural effusion  1  0/258 (0.00%)  0 7/265 (2.64%)  7
Pneumonia aspiration  1  1/258 (0.39%)  1 1/265 (0.38%)  1
Pneumonitis  1  2/258 (0.78%)  2 1/265 (0.38%)  1
Pneumothorax  1  1/258 (0.39%)  1 0/265 (0.00%)  0
Pulmonary embolism  1  1/258 (0.39%)  1 2/265 (0.75%)  2
Pulmonary hypertension  1  0/258 (0.00%)  0 1/265 (0.38%)  1
Skin and subcutaneous tissue disorders     
Dermatitis  1  0/258 (0.00%)  0 1/265 (0.38%)  1
Rash generalised  1  1/258 (0.39%)  1 0/265 (0.00%)  0
Vascular disorders     
Aortic aneurysm  1  0/258 (0.00%)  0 1/265 (0.38%)  1
Arterial haemorrhage  1  0/258 (0.00%)  0 1/265 (0.38%)  1
Deep vein thrombosis  1  2/258 (0.78%)  2 2/265 (0.75%)  2
Embolism  1  1/258 (0.39%)  1 1/265 (0.38%)  1
Haematoma  1  0/258 (0.00%)  0 1/265 (0.38%)  1
Hypertension  1  2/258 (0.78%)  2 0/265 (0.00%)  0
Hypotension  1  0/258 (0.00%)  0 1/265 (0.38%)  1
Venous occlusion  1  0/258 (0.00%)  0 1/265 (0.38%)  1
1
Term from vocabulary, MedDRA 20.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Ramucirumab + Docetaxel Placebo + Docetaxel
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   234/258 (90.70%)      243/265 (91.70%)    
Blood and lymphatic system disorders     
Anaemia  1  40/258 (15.50%)  65 61/265 (23.02%)  99
Neutropenia  1  17/258 (6.59%)  34 13/265 (4.91%)  13
Eye disorders     
Lacrimation increased  1  23/258 (8.91%)  25 10/265 (3.77%)  10
Gastrointestinal disorders     
Abdominal pain  1  15/258 (5.81%)  20 15/265 (5.66%)  20
Constipation  1  29/258 (11.24%)  38 42/265 (15.85%)  56
Diarrhoea  1  72/258 (27.91%)  106 55/265 (20.75%)  77
Nausea  1  62/258 (24.03%)  85 50/265 (18.87%)  73
Stomatitis  1  61/258 (23.64%)  105 29/265 (10.94%)  33
Vomiting  1  36/258 (13.95%)  55 36/265 (13.58%)  49
General disorders     
Asthenia  1  26/258 (10.08%)  49 22/265 (8.30%)  36
Fatigue  1  85/258 (32.95%)  160 100/265 (37.74%)  164
Malaise  1  17/258 (6.59%)  27 10/265 (3.77%)  16
Oedema peripheral  1  36/258 (13.95%)  49 30/265 (11.32%)  38
Pyrexia  1  40/258 (15.50%)  62 36/265 (13.58%)  53
Infections and infestations     
Urinary tract infection  1  27/258 (10.47%)  34 29/265 (10.94%)  31
Investigations     
Neutrophil count decreased  1  29/258 (11.24%)  92 29/265 (10.94%)  71
Platelet count decreased  1  18/258 (6.98%)  49 6/265 (2.26%)  9
Weight decreased  1  22/258 (8.53%)  25 19/265 (7.17%)  25
White blood cell count decreased  1  19/258 (7.36%)  70 20/265 (7.55%)  50
Metabolism and nutrition disorders     
Decreased appetite  1  73/258 (28.29%)  113 61/265 (23.02%)  78
Hypoalbuminaemia  1  15/258 (5.81%)  20 19/265 (7.17%)  22
Musculoskeletal and connective tissue disorders     
Arthralgia  1  19/258 (7.36%)  23 21/265 (7.92%)  27
Back pain  1  25/258 (9.69%)  31 17/265 (6.42%)  22
Bone pain  1  13/258 (5.04%)  13 16/265 (6.04%)  17
Myalgia  1  24/258 (9.30%)  37 22/265 (8.30%)  28
Pain in extremity  1  10/258 (3.88%)  12 15/265 (5.66%)  19
Nervous system disorders     
Dysgeusia  1  30/258 (11.63%)  41 17/265 (6.42%)  18
Headache  1  18/258 (6.98%)  25 13/265 (4.91%)  14
Peripheral sensory neuropathy  1  16/258 (6.20%)  21 19/265 (7.17%)  26
Psychiatric disorders     
Insomnia  1  17/258 (6.59%)  17 9/265 (3.40%)  10
Renal and urinary disorders     
Haematuria  1  26/258 (10.08%)  40 14/265 (5.28%)  14
Proteinuria  1  23/258 (8.91%)  33 8/265 (3.02%)  10
Respiratory, thoracic and mediastinal disorders     
Cough  1  19/258 (7.36%)  24 23/265 (8.68%)  26
Dyspnoea  1  28/258 (10.85%)  45 29/265 (10.94%)  33
Epistaxis  1  36/258 (13.95%)  52 13/265 (4.91%)  14
Hiccups  1  14/258 (5.43%)  21 7/265 (2.64%)  7
Skin and subcutaneous tissue disorders     
Alopecia  1  63/258 (24.42%)  73 92/265 (34.72%)  112
Nail discolouration  1  5/258 (1.94%)  5 14/265 (5.28%)  14
Palmar-plantar erythrodysaesthesia syndrome  1  18/258 (6.98%)  25 5/265 (1.89%)  11
Rash  1  9/258 (3.49%)  12 14/265 (5.28%)  17
Vascular disorders     
Hypertension  1  26/258 (10.08%)  43 9/265 (3.40%)  9
1
Term from vocabulary, MedDRA 20.0
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
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Petrylak DP, de Wit R, Chi KN, Drakaki A, Sternberg CN, Nishiyama H, Castellano D, Hussain SA, Fléchon A, Bamias A, Yu EY, van der Heijden MS, Matsubara N, Alekseev B, Necchi A, Géczi L, Ou YC, Coskun HS, Su WP, Bedke J, Gakis G, Percent IJ, Lee JL, Tucci M, Semenov A, Laestadius F, Peer A, Tortora G, Safina S, Garcia Del Muro X, Rodriguez-Vida A, Cicin I, Harputluoglu H, Tagawa ST, Vaishampayan U, Aragon-Ching JB, Hamid O, Liepa AM, Wijayawardana S, Russo F, Walgren RA, Zimmermann AH, Hozak RR, Bell-McGuinn KM, Powles T; RANGE study investigators. Ramucirumab plus docetaxel versus placebo plus docetaxel in patients with locally advanced or metastatic urothelial carcinoma after platinum-based therapy (RANGE): overall survival and updated results of a randomised, double-blind, phase 3 trial. Lancet Oncol. 2020 Jan;21(1):105-120. doi: 10.1016/S1470-2045(19)30668-0. Epub 2019 Nov 18.
Layout table for additonal information
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT02426125    
Other Study ID Numbers: 15679
I4T-MC-JVDC ( Other Identifier: Eli Lilly and Company )
2014-003655-66 ( EudraCT Number )
First Submitted: April 21, 2015
First Posted: April 24, 2015
Results First Submitted: January 25, 2019
Results First Posted: March 8, 2019
Last Update Posted: July 14, 2020