Urothelial Carcinoma
Conditions
Keywords
carcinoma of the bladder, carcinoma of the urethra, carcinoma the of ureter, carcinoma of the renal pelvis, transitional cell carcinoma, transitional cell tumor, RANGE, bladder cancer
Brief summary
The main purpose of this study is to evaluate the safety and efficacy of the study drug ramucirumab in combination with docetaxel in participants with urothelial cancer who failed prior platinum-based therapy.
Interventions
DRUGRamucirumab
Administered IV
DRUGDocetaxel
Administered IV
DRUGPlacebo
Administered IV
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have histologically or cytologically confirmed, locally advanced or unresectable or metastatic urothelial (transitional cell) carcinoma of the bladder, urethra, ureter, or renal pelvis. * Had disease progression while on a platinum containing regimen in the first-line setting or within 14 months after completing the first-line platinum regimen. Participants who received treatment with one immune checkpoint inhibitor regimen are eligible (for example Programmed death 1 (PD-1), Programmed death-ligand 1 (PDL1), or CTLA4) and may have a longer interval since prior platinum-containing therapy (≤24 months). * Have a life expectancy of ≥3 months. * Have received no more than one prior systemic chemotherapy regimen in the relapsed or metastatic setting. Prior treatment with no more than one prior immune checkpoint inhibitor is permitted and will not be considered as a line of systemic chemotherapy. * Have measurable disease or nonmeasurable but evaluable disease as defined by Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1). * Have an Eastern Cooperative Oncology Group (ECOG) of 0 or 1. * Have adequate hematologic function. * Have adequate coagulation function. * Have adequate hepatic function. * The participant does not have: * cirrhosis at a level of Child-Pugh B (or worse) * cirrhosis (any degree) and a history of hepatic encephalopathy or clinically meaningful ascites resulting from cirrhosis * Have adequate renal function as defined by creatinine clearance \>30 milliliters/minute. * Have urinary protein ≤1+ on dipstick or routine urinalysis. * The participant is willing to provide blood, urine, and tissue samples for research purposes.
Exclusion criteria
* Have received more than one prior systemic chemotherapy regimen for metastatic disease. * Have received prior systemic taxane therapy for transitional cell carcinoma (TCC) of the bladder, urethra, ureter, or renal pelvis in any setting (neoadjuvant, adjuvant, metastatic). * Have received more than one prior antiangiogenic agent (that is, bevacizumab, sorafenib, sunitinib) for TCC of the urothelium. * Have received radiation therapy within 4 weeks (≤4 weeks) prior to randomization or has not recovered from toxic effects of the treatment that was given \>4 weeks prior to randomization. * Have a history of uncontrolled hereditary or acquired bleeding or thrombotic disorders. * Have experienced a Grade ≥3 bleeding event within 3 months (≤3 months) prior to randomization. * Have uncontrolled intercurrent illness, including, but not limited to symptomatic anemia, uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, symptomatic or poorly controlled cardiac arrhythmia, psychiatric illness, or any other serious uncontrolled medical disorders. * Have experienced any arterial or venothrombotic or thromboembolic events, including, but not limited to myocardial infarction, transient ischemic attack, or cerebrovascular accident, within 6 months (≤6 months) prior to randomization. * Have known untreated brain metastases, uncontrolled spinal cord compression, or leptomeningeal disease. * Have human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome-related illness. * Have undergone major surgery within 28 days (≤28 days) prior to randomization or subcutaneous venous access device placement within 7 days (≤7 days) prior to randomization. * The participant is pregnant prior to randomization or lactating. * Have a concurrent malignancy or had another malignancy within 5 years (≤5 years) of study enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | Randomization to Radiological Disease Progression or Death from Any Cause (Up to 18 Months) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With an Objective Response Rate (ORR) | Randomization to Disease Progression (Up to 29.7 Months) | ORR 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 defined as disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to \< 10 millimeter (mm). Tumor-marker results must have normalized. PR is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Best overall response is classified based on the overall responses assessed by study investigators according to RECIST v1.1. |
| Percentage of Participants With Disease Control Rate (DCR) | Randomization to Disease Progression (Up to 29.7 Months) | 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). |
| Duration of Response (DoR) | Date of Complete Response (CR) or Partial Response (PR) to Date of Objective Disease Progression or Death Due to Any Cause (Up to 28.4 Months) | 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 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 | Randomization, 30 Days After Treatment Discontinuation (Up to 18 Months) | 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. |
| Overall Survival (OS) | Randomization to Date of Death from Any Cause (Up to 31.1 Months) | 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. |
| Change From Baseline on the EuroQol 5-Dimension, 5-Level Questionnaire (EQ-5D-5L) Visual Analogue Scale (VAS) | Randomization, 30 Days After Treatment Discontinuation (Up to 18 Months) | 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 VAS ranging from 100 (best imaginable health state) to 0 (worst imaginable health state). |
| Pharmacokinetics (PK): Maximum Concentration (Cmax) of Ramucirumab | Cycle 1 and Cycle 9, Day 1: Predose, Postdose | Cmax of Ramucirumab at the end of ramucirumab infusion. |
| PK: Minimum Concentration (Cmin) of Ramucirumab | Day 1 of Cycle 2, 3, 5 and 9 (Predose and Postdose) | Cmin of Ramucirumab following administration every 3 weeks. |
| Number of Participants With Anti-Ramucirumab Antibodies | 29.7 Months | Number of participants with positive treatment emergent anti-ramucirumab antibodies was summarized by treatment group. |
| Change From Baseline on the EuroQol 5-Dimension, 5-Level Questionnaire (EQ-5D-5L) Index Score | Randomization, 30 Days After Treatment Discontinuation (Up to 18 Months) | 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. |
Countries
Australia, Belgium, Canada, Denmark, France, Germany, Greece, Hungary, Israel, Italy, Japan, Mexico, Netherlands, Poland, Romania, Russia, South Korea, Spain, Taiwan, Turkey (Türkiye), Ukraine, United Kingdom, United States
Participant flow
Pre-assignment details
Completers include participants who are confirmed to be alive at study completion.
Participants by arm
| Arm | Count |
|---|---|
| Ramucirumab + Docetaxel Ramucirumab (10 mg/kg) IV plus docetaxel (75 mg/m²) IV on day 1 of each 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met. | 263 |
| Placebo + Docetaxel Placebo IV plus docetaxel (75 mg/m²) IV on day 1 of each 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met. | 267 |
| Total | 530 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 185 | 200 |
| Overall Study | Lost to Follow-up | 14 | 12 |
| Overall Study | Randomized, But Never Treated | 5 | 2 |
| Overall Study | Withdrawal by Subject | 13 | 14 |
Baseline characteristics
| Characteristic | Placebo + Docetaxel | Total | Ramucirumab + Docetaxel |
|---|---|---|---|
| Age, Continuous | 64.8 years STANDARD_DEVIATION 9.2 | 64.7 years STANDARD_DEVIATION 9.6 | 64.6 years STANDARD_DEVIATION 9.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants | 23 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 219 Participants | 427 Participants | 208 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 38 Participants | 80 Participants | 42 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 61 Participants | 115 Participants | 54 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 5 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) White | 204 Participants | 407 Participants | 203 Participants |
| Region of Enrollment Australia | 6 Participants | 12 Participants | 6 Participants |
| Region of Enrollment Belgium | 1 Participants | 7 Participants | 6 Participants |
| Region of Enrollment Canada | 5 Participants | 9 Participants | 4 Participants |
| Region of Enrollment Denmark | 6 Participants | 11 Participants | 5 Participants |
| Region of Enrollment France | 18 Participants | 34 Participants | 16 Participants |
| Region of Enrollment Germany | 11 Participants | 16 Participants | 5 Participants |
| Region of Enrollment Greece | 13 Participants | 26 Participants | 13 Participants |
| Region of Enrollment Hungary | 8 Participants | 13 Participants | 5 Participants |
| Region of Enrollment Israel | 11 Participants | 18 Participants | 7 Participants |
| Region of Enrollment Italy | 14 Participants | 37 Participants | 23 Participants |
| Region of Enrollment Japan | 30 Participants | 54 Participants | 24 Participants |
| Region of Enrollment Mexico | 1 Participants | 4 Participants | 3 Participants |
| Region of Enrollment Netherlands | 18 Participants | 35 Participants | 17 Participants |
| Region of Enrollment Poland | 4 Participants | 8 Participants | 4 Participants |
| Region of Enrollment Romania | 5 Participants | 10 Participants | 5 Participants |
| Region of Enrollment Russia | 12 Participants | 30 Participants | 18 Participants |
| Region of Enrollment South Korea | 9 Participants | 25 Participants | 16 Participants |
| Region of Enrollment Spain | 15 Participants | 37 Participants | 22 Participants |
| Region of Enrollment Taiwan | 18 Participants | 31 Participants | 13 Participants |
| Region of Enrollment Turkey | 17 Participants | 28 Participants | 11 Participants |
| Region of Enrollment Ukraine | 3 Participants | 8 Participants | 5 Participants |
| Region of Enrollment United Kingdom | 24 Participants | 42 Participants | 18 Participants |
| Region of Enrollment United States | 18 Participants | 35 Participants | 17 Participants |
| Sex: Female, Male Female | 52 Participants | 102 Participants | 50 Participants |
| Sex: Female, Male Male | 215 Participants | 428 Participants | 213 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 193 / 258 | 209 / 265 |
| other Total, other adverse events | 241 / 258 | 251 / 265 |
| serious Total, serious adverse events | 111 / 258 | 107 / 265 |
Outcome results
Primary
Progression Free Survival (PFS)
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)
Population: The first randomized participants. Censored participants: Ramucirumab + Docetaxel = 58, Placebo + Docetaxel =38.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ramucirumab + Docetaxel | Progression Free Survival (PFS) | 4.07 Months |
| Placebo + Docetaxel | Progression Free Survival (PFS) | 2.76 Months |
p-value: 0.011895% CI: [0.607, 0.943]Log Rank
Secondary
Change From Baseline on the EuroQol 5-Dimension, 5-Level Questionnaire (EQ-5D-5L) Index Score
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)
Population: All randomized participants with baseline and 30-day follow-up data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ramucirumab + Docetaxel | Change From Baseline on the EuroQol 5-Dimension, 5-Level Questionnaire (EQ-5D-5L) Index Score | -0.10 units on a scale | Standard Deviation 0.26 |
| Placebo + Docetaxel | Change From Baseline on the EuroQol 5-Dimension, 5-Level Questionnaire (EQ-5D-5L) Index Score | -0.19 units on a scale | Standard Deviation 0.26 |
Secondary
Change From Baseline on the EuroQol 5-Dimension, 5-Level Questionnaire (EQ-5D-5L) Visual Analogue Scale (VAS)
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 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)
Population: All randomized participants with baseline and 30-day follow-up data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ramucirumab + Docetaxel | Change From Baseline on the EuroQol 5-Dimension, 5-Level Questionnaire (EQ-5D-5L) Visual Analogue Scale (VAS) | -7.87 millimeter (mm) | Standard Deviation 17.95 |
| Placebo + Docetaxel | Change From Baseline on the EuroQol 5-Dimension, 5-Level Questionnaire (EQ-5D-5L) Visual Analogue Scale (VAS) | -10.91 millimeter (mm) | Standard Deviation 16.77 |
Secondary
Duration of Response (DoR)
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 28.4 Months)
Population: All randomized participants with CR or PR. Participants censored in Ramucirumab + Docetaxel = 12 and in Placebo + Docetaxel = 5.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ramucirumab + Docetaxel | Duration of Response (DoR) | 5.32 Months |
| Placebo + Docetaxel | Duration of Response (DoR) | 4.17 Months |
p-value: 0.18995% CI: [0.473, 1.158]Log Rank
Secondary
Number of Participants With Anti-Ramucirumab Antibodies
Number of participants with positive treatment emergent anti-ramucirumab antibodies was summarized by treatment group.
Time frame: 29.7 Months
Population: All randomized participants who received at least one dose of study drug at baseline and post-baseline.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ramucirumab + Docetaxel | Number of Participants With Anti-Ramucirumab Antibodies | 3 Participants |
| Placebo + Docetaxel | Number of Participants With Anti-Ramucirumab Antibodies | 8 Participants |
Secondary
Overall Survival (OS)
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 31.1 Months)
Population: All randomized participants. Censored participants: Ramucirumab + Docetaxel = 78, Placebo + Docetaxel = 67.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ramucirumab + Docetaxel | Overall Survival (OS) | 9.40 Months |
| Placebo + Docetaxel | Overall Survival (OS) | 7.85 Months |
p-value: 0.246195% CI: [0.724, 1.086]Log Rank
Secondary
Percentage of Participants With an Objective Response Rate (ORR)
ORR 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 defined as disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to \< 10 millimeter (mm). Tumor-marker results must have normalized. PR is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Best overall response is classified based on the overall responses assessed by study investigators according to RECIST v1.1.
Time frame: Randomization to Disease Progression (Up to 29.7 Months)
Population: All randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ramucirumab + Docetaxel | Percentage of Participants With an Objective Response Rate (ORR) | 25.9 percentage of participants |
| Placebo + Docetaxel | Percentage of Participants With an Objective Response Rate (ORR) | 13.9 percentage of participants |
Secondary
Percentage of Participants With Disease Control Rate (DCR)
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 29.7 Months)
Population: All randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ramucirumab + Docetaxel | Percentage of Participants With Disease Control Rate (DCR) | 65.4 percentage of participants |
| Placebo + Docetaxel | Percentage of Participants With Disease Control Rate (DCR) | 55.1 percentage of participants |
Secondary
Pharmacokinetics (PK): Maximum Concentration (Cmax) of Ramucirumab
Cmax of Ramucirumab at the end of ramucirumab infusion.
Time frame: Cycle 1 and Cycle 9, Day 1: Predose, Postdose
Population: All randomized participants who had evaluable PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Ramucirumab + Docetaxel | Pharmacokinetics (PK): Maximum Concentration (Cmax) of Ramucirumab | Cycle 1 | 199 microgram/milliliter (μg/mL) | Geometric Coefficient of Variation 28 |
| Ramucirumab + Docetaxel | Pharmacokinetics (PK): Maximum Concentration (Cmax) of Ramucirumab | Cycle 9 | 265 microgram/milliliter (μg/mL) | Geometric Coefficient of Variation 29 |
Secondary
PK: Minimum Concentration (Cmin) of Ramucirumab
Cmin of Ramucirumab following administration every 3 weeks.
Time frame: Day 1 of Cycle 2, 3, 5 and 9 (Predose and Postdose)
Population: All randomized participants who had evaluable PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Ramucirumab + Docetaxel | PK: Minimum Concentration (Cmin) of Ramucirumab | Cycle 2 | 14.9 μg/mL | Geometric Coefficient of Variation 64 |
| Ramucirumab + Docetaxel | PK: Minimum Concentration (Cmin) of Ramucirumab | Cycle 3 | 23.5 μg/mL | Geometric Coefficient of Variation 63 |
| Ramucirumab + Docetaxel | PK: Minimum Concentration (Cmin) of Ramucirumab | Cycle 5 | 32.5 μg/mL | Geometric Coefficient of Variation 70 |
| Ramucirumab + Docetaxel | PK: Minimum Concentration (Cmin) of Ramucirumab | Cycle 9 | 48.9 μg/mL | Geometric Coefficient of Variation 56 |
Secondary
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
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)
Population: All randomized participants. Censored participants: Ramucirumab + Docetaxel = 160, Placebo + Docetaxel = 173.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ramucirumab + Docetaxel | 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 | 6.87 Months |
| Placebo + Docetaxel | 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 | 4.60 Months |
Comparison: Global health status/QoLp-value: 0.35795% CI: [0.663, 1.167]Log Rank