The research study is testing the investigational drug necitumumab (IMC-11F8) in the treatment of advanced non-small cell lung cancer. The aim of this study is to determine if necitumumab, given together with a standard chemotherapy combination consisting of cisplatin and gemcitabine will be more effective in improving participant disease than the standard chemotherapy combination alone.
Multinational, randomized, multicenter, open-label, Phase III study of 1093 participants (age ≥ 18 years) with histologically- or cytologically-confirmed, stage IV squamous-cell NSCLC, who have received no prior therapy for metastatic disease, will be randomized on a 1:1 basis to receive first-line necitumumab plus chemotherapy consisting of gemcitabine and cisplatin in study Arm A, or gemcitabine-cisplatin chemotherapy alone in study Arm B. Baseline radiographic assessment of disease will be performed within 21 days prior to randomization (first treatment will be administered within 7 days following randomization). Participants will undergo radiographic assessment of disease status (computed tomography or magnetic resonance imaging) every 6 weeks (± 3 days), until there is radiographic documentation of progressive disease (PD). Chemotherapy will continue for a maximum of six cycles in each arm (or until there is radiographic documentation of PD, toxicity requiring cessation, protocol noncompliance or withdrawal of consent); participants in Arm A only will continue to receive necitumumab until there is radiographic documentation of PD, toxicity requiring cessation, protocol noncompliance, or withdrawal of consent. After the end-of-study-visit (following PD), follow-up information regarding further anticancer treatment and survival will be collected every 2 months (± 7 days). For participants who discontinue study for reasons other than PD (eg, symptomatic deterioration), information on disease progression will also be collected until PD is documented. Follow-up will continue as long as the participant is alive, or until the end of the trial.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
1,093
Administered intravenously. Continues until progressive disease, toxicity, noncompliance, or withdrawal.
Administered intravenously. Continues for a maximum of six cycles.
Administered intravenously. Continues for a maximum of six cycles.
Overall Survival Time (OS)
Overall survival is defined as the time from randomization to death from any cause. Participants who do not die at the end of the extended follow-up period, or were lost to follow-up during the study, were censored at the last date they were known to be alive. OS was estimated by the Kaplan-Meier method.
Time frame: Randomization to Death from Any Cause (Up to 31 Months)
Progression-Free Survival (PFS)
PFS is defined as the time from randomization until the first radiographic documentation of objective measured progressive disease as defined by RECIST (Version 1.0), or death from any cause. Progressive Disease (PD) was defined as having at least a 20% increase in the sum of the longest diameter of target lesions. Participants who die without a reported prior progression were considered to have progressed on the day of their death. Participants who did not progress or were lost to follow-up were censored at the day of their last radiographic tumor assessment. If no baseline or postbaseline radiologic assessment was available, the participants were censored at the date of randomization. If death or PD occurs after two or more consecutive missing radiographic visits, censoring occurred at the date of the last radiographic visit prior to the missed visits.
Time frame: Randomization to Measured Progressive Disease or Death from Any Cause (Up to 31 Months)
Percentage of Participants Achieving Complete Response (CR) and Partial Response (PR) (Objective Response Rate [ORR])
ORR is confirmed best overall tumor response of CR or PR. According to RECIST v1.0, CR was defined as the disappearance of all target and non-target lesions. PR defined as a \>=30% decrease in the sum of the longest diameters (LD) of the target lesions, taking as reference the baseline sum of the LD; Percentage of participants was calculated as: (total number of participants with CR or PR from start of the treatment until disease progression or recurrence)/total number of participants treated) \* 100.
Time frame: Baseline to Measured Progressive Disease (Up to 31 Months)
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
ImClone Investigational Site
Chandler, Arizona, United States
ImClone Investigational Site
Fayetteville, Arkansas, United States
ImClone Investigational Site
Sacramento, California, United States
ImClone Investigational Site
Galesburg, Illinois, United States
ImClone Investigational Site
Goshen, Indiana, United States
ImClone Investigational Site
Wichita, Kansas, United States
ImClone Investigational Site
Hazard, Kentucky, United States
ImClone Investigational Site
Baltimore, Maryland, United States
ImClone Investigational Site
Jefferson City, Missouri, United States
ImClone Investigational Site
Lincoln, Nebraska, United States
...and 172 more locations
Time to Treatment Failure (TTF)
TTF is defined as the time from the date of randomization until the date of the first radiographic documentation of PD, death from any cause, discontinuation of treatment for any reason, or initiation of new cancer therapy. Participants who withdrew from the study for reasons other than progression or death were censored at the date of study withdrawal. Participants who did not meet any of the criteria for treatment failure were censored at their date of last contact in the study.
Time frame: Randomization to Measured Progressive Disease, Death From Any Cause, Discontinuation of Treatment or Initiation of New Anticancer Therapy (Up to 31 Months)
Mean Change From Baseline in Patient Reported Outcomes (PRO) Using the European Quality of Life-5 Dimension (EQ-5D)
The EQ-5D is a generic, multidimensional, health-related, quality-of-life instrument. The profile allows participants to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression using a three level scale 1-3 (no problem, some problems, and major problems). These combinations of attributes were converted into a weighted health-state Index Score according to the United Kingdom (UK) population-based algorithm. The possible values for the Index Score ranged from -0.59 (severe problems in all 5 dimensions) to 1.0 (no problem in any dimension).
Time frame: Baseline, Cycle 6 (Cycle = 3 Weeks)
Mean Change From Baseline in PRO Using the Outcomes 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. Scores for each of the reported categories ranged from 0 (for best outcome) to 100 (for worst outcome). 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.
Time frame: Baseline, Cycle 6 (Cycle = 3 Weeks)
Number of Participants With an Epidermal Growth Factor Hormone (EGFR) Protein Expression Measured by Immunohistochemistry (IHC)
EGFR IHC Histoscore H-score = weighted sum of % 1+ cells, twice % 2+ cells, and three times % 3+ cells. IHC H-score criteria was used to assess participants with a low EGFR expression defined by a H-score cutoff value of \<200 and participants with a high EGFR expression defined by a H-score of cutoff value of \>=200.
Time frame: 31 Months
Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab
Time frame: Day 1 of Cycle 2, 3, 4, 5 and 6 Prior to Necitumumab Drug Infusion, Up to 24 Months
Number of Participants With a Serum Anti-Necitumumab Antibody Assessment
A participant was considered to have an anti-Necitumumab antibody response if anti-drug antibodies (ADA) were detected at any time point.
Time frame: Baseline through 31 Months