The purpose of this study is to determine if participants with untreated locally advanced or metastatic non-small cell lung cancer have a better outcome when treated with olaratumab in combination with paclitaxel/carboplatin then when treated with paclitaxel/carboplatin alone.
The primary objective of this study is to evaluate the progression-free survival (PFS) in previously untreated participants with Stage IIIB/IV non-small cell lung cancer (NSCLC) treated with olaratumab plus paclitaxel and carboplatin versus paclitaxel and carboplatin in the first-line metastatic setting.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
137
15 mg/kg of olaratumab on Days 1 and 8 of each 21-day cycle, administered intravenously (IV) at 25 milligram/minute (mg/min), with a minimum infusion time of 30 minutes.
200 mg/m2 is then administered IV over 3 hours
AUC=6 administered IV over 30 minutes on Day 1 of each 3-week cycle for a maximum of six cycles. Once the maximum of 6 cycles of carboplatin are reached the participant may continue on olaratumab maintenance for up to 12 months.
ImClone Investigational Site
Birmingham, Alabama, United States
Progression-Free Survival (PFS)
PFS is defined as the time from the day of randomization to the first evidence of progression by RECIST version 1.1, or death from any cause. Participants who died without a reported prior progression were considered to have progressed on the day of their death. Participants who did not progress and were subsequently lost to follow-up had their data censored at the day of their last tumor assessment. If there was no radiologic assessment at baseline or post baseline, participants were censored at the date of randomization. If death or progressive disease (PD) occurred after 2 or more consecutive missing radiographic visits, censoring occurred at the date of the last radiographic visit prior to the missed visits.
Time frame: Baseline to Measured PD or Death From Any Cause (Up to 31 Months)
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
A summary of other nonserious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section.
Time frame: Baseline to Study Completion (Up to 43 Months)
Safety and Tolerability of Olaratumab Administered at a More Rapid Rate (25mg/Min With Minimum Infusion Time of 30 Minutes), Determined by Number of Participants With Treatment Related Adverse Events
Time frame: Up to 43 Months
Overall Survival (OS)
Overall survival is defined as the time from date of randomization to the date of death from any cause. If the participant is alive at the end of the follow-up period or is lost to follow-up, OS was censored on the last date the participants is known to be alive.
Time frame: Baseline to Death From Any Cause (Up to 31 Months)
Percentage of Participants Who Achieve Best Overall Tumor Response of Complete Response (CR) or Partial Response (PR) Objective Tumor Response Rate (ORR)
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ImClone Investigational Site
Bakersfield, California, United States
ImClone Investigational Site
Highland, California, United States
ImClone Investigational Site
Stamford, Connecticut, United States
ImClone Investigational Site
Port Saint Lucie, Florida, United States
ImClone Investigational Site
Joliet, Illinois, United States
ImClone Investigational Site
Baton Rouge, Louisiana, United States
ImClone Investigational Site
St Louis, Missouri, United States
ImClone Investigational Site
Charlotte, North Carolina, United States
ImClone Investigational Site
Gastonia, North Carolina, United States
...and 13 more locations
The ORR is equal to the percentage of participants achieving a best overall response of partial response or complete response (PR + CR), according to RECIST version 1.1 criteria. CR was defined as the disappearance of all target and non-target lesions and any pathological lymph nodes must have reduction in short axis to \<10 millimeter (mm) and normalization of tumor marker level of non-target lesions; PR was defined as having at least a 30% decrease in sum of longest diameter of target lesions; PD was defined as having at least 20% increase in sum of longest diameter of target lesions and minimum 5 mm increase above nadir; Stable Disease (SD) was defined as small changes that did not meet above criteria. Participants who had no post baseline tumor assessments were considered non-responders and included in the denominator when calculating response rate. Percentage of participants=(number of participants with CR+PR/total number of participants)\*100.
Time frame: Baseline to Measured PD or Study Discontinuation (Up to 31 Months)
Median Duration of Response
The duration of overall response is measured from the time measurement criteria are first met for Complete Response (CR)/Partial Response (PR) (whichever is first recorded) until the first date that the criteria for PD are met (taking as a reference for PD the smallest measurement recorded since the treatment started), initiation of other/additional antitumor therapy is first reported, or death, is objectively documented.
Time frame: First Criteria Met for CR or PR to Measured PD Start of Other Antitumor Therapy or Death From Any Cause (Up to 31 Months)
Pharmacodynamics of Olaratumab
Pharmacodynamics of Olaratumab was determined by analysis of pharmacodynamic markers vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF).
Time frame: Cycle 1: Days 1, 8, and 15 pre- and post-infusion of Olaratumab; Cycles 2-6: day 1 only, pre- and post-infusion of Olaratumab
Percentage of Participants With Anti-Olaratumab Antibodies
Participants with Treatment Emergent (TE) anti-olaratumab antibodies were participants with a 4-fold increase (2 dilutions) increase over a positive baseline antibody titer or for a negative baseline titer, a participant with an increase from the baseline to a level of 1:20.
Time frame: Baseline to Study Completion (Up to 8 Months)
Pharmacokinetics (PK) - Area Under the Curve (AUC) 0-168 of Olaratumab
AUC(0-168) = area under the concentration versus time curve from time zero to 168 hours post dose.
Time frame: Cycle 3, Day 1: Predose, 30 minutes (min), 1.5 hours (hrs), 24,48,96,168 Hrs Post Dose
PK - Maximum Concentration (Cmax) of Olaratumab
Time frame: Cycle 3, Day 1: Predose, 30 min, 1.5 hrs, 24,48,96,168 Hrs Post Dose
PK - Half-Life (t1/2) of Olaratumab
Time frame: Cycle 3, Day 1: Predose, 30 min, 1.5 hrs, 24,48,96,168 Hrs Post Dose
PK - Clearance (Cl) of Olaratumab
Time frame: Cycle 3, Day 1: Predose, 30 min, 1.5 hr, 24,48,96,168 Hrs Post Dose
PK - Steady State Volume of Distribution (Vss) of Olaratumab
Time frame: Cycle 3, Day 1: Predose, 30 min, 1.5 hrs, 24,48,96,168 Hrs Post Dose