The purpose of the study is to compare the survival of participants who receive chemotherapy and ramucirumab versus chemotherapy alone as second line treatment for NSCLC after prior first line platinum-based chemotherapy.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
1,253
10 milligrams per kilogram (mg/kg) administered intravenously (IV) on Day 1 of 21-day cycle until disease progression, unacceptable toxicity, or another withdrawal criterion is met
Administered IV on Day 1 of 21-day cycle until disease progression, unacceptable toxicity, or another withdrawal criterion is met
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 IV on Day 1 of 21-day cycle until disease progression, unacceptable toxicity, or another withdrawal criterion is met
Overall Survival
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)
Progression-Free Survival (PFS) Time
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)
Percentage of Participants Achieving an Objective Response (Objective Response Rate)
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.
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For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Phoenix, Arizona, United States
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Sedona, Arizona, United States
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Fayetteville, Arkansas, United States
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Alhambra, California, United States
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Duarte, California, United States
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Fresno, California, United States
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Fullerton, California, United States
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La Jolla, California, United States
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Long Beach, California, United States
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Los Angeles, California, United States
...and 221 more locations
Time frame: Baseline to measured PD (up to 29 months)
Percentage of Participants Achieving Disease Control (Disease Control Rate)
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)
Maximum Improvement on Lung Cancer Symptom Scale (LCSS)
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)
Change From Baseline to 30-Day Follow-Up Visit on European Quality of Life Questionnaire-5 Dimension (EQ-5D) Health State Scores
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)
Maximum and Minimum Serum Concentrations (Cmax and Cmin) of Ramucirumab
Time frame: Prior to infusion and 1 hour following infusion for 4 and 8 (cycles 3 and 5 at 21 days/cycle)
Number of Participants With Anti-Ramucirumab Antibodies
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)