A Study of Docetaxel and Ramucirumab Versus Docetaxel and Placebo in the Treatment of Stage IV Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effects of ramucirumab in combination with docetaxel in participants with Stage IV non-small cell lung cancer who have had disease progression during or after one prior first-line platinum-based chemotherapy with or without maintenance therapy for advanced/metastatic disease.

Official Title
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A Randomized, Double-Blind, Phase 2 Study of Docetaxel and Ramucirumab Versus Docetaxel and Placebo in the Treatment of Stage IV Non-Small Cell Lung Cancer Following Disease Progression After One Prior Platinum-Based Therapy

Conditions
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Non-small Cell Lung Cancer Metastatic

Intervention / Treatment
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* Drug: Ramucirumab
* Drug: Placebo
* Drug: Docetaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Non-Small Cell Lung Cancer disease Clinical stage IV or recurrent disease One prior first-line platinum-based chemotherapy regimen with or without maintenance therapy For Non-Small Cell Lung Cancer (NSCLC) tumors other than squamous cell histology, the epidermal growth factor receptor (EGFR) mutation status is known prior to randomization For participants with activating epidermal growth factor receptor (EGFR) mutation only, prior epidermal growth factor receptor- tyrosine kinase inhibitor (EGFR-TKI) monotherapy (only one regimen in the setting of single use) should be utilized Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1 Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version RECIST version 1.1 Adequate organ function Estimated life expectancy of at least 3 months. Exclusion Criteria: Have undergone major surgery within 28 days prior to randomization or have planned major surgery during study treatment Receiving concurrent treatment with other anticancer therapy Central nervous system disease other than stable and treated brain metastasis Has major blood vessel invasion or encasement by cancer Has intratumor cavitation Has a history of uncontrolled thrombotic disorder Is receiving therapeutic anticoagulation with drugs Is receiving chronic therapy with nonsteroidal anti-inflammatory drugs Has a history of hemoptysis within 2 months prior to randomization Has clinically relevant congestive heart failure Has experienced any arterial thromboembolic event Has uncontrolled arterial hypertension Has had a serious or nonhealing wound or, ulcer Has significant existing conditions

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ramucirumab plus Docetaxel<br>Ramucirumab 10 milligram per kilogram (mg/kg) on Day 1 of every 21 day cycle, administered as an intravenous (IV) infusion over approximately 60 minutes. Docetaxel 60 milligram per square meter (mg/m2) on Day 1 of every 21 day cycle, administered as an IV infusion over approximately 60 minutes. | Drug: Ramucirumab<br>* Administered IV<br>* Other names: Cyramza®;Drug: Docetaxel<br>* Administered IV<br>|
| Placebo Comparator: Placebo plus Docetaxel<br>Placebo (administered at a volume equivalent to a dose of milligram per kilogram (mg/kg)) on Day 1 of every 21 day cycle, administered as an IV infusion over approximately 60 minutes. Docetaxel 60 mg/m2 on Day 1 of every 21 day cycle, administered as an IV infusion over approximately 60 minutes. | Drug: Placebo<br>* Administered IV<br>Drug: Docetaxel<br>* Administered IV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) | PFS was defined as the time from baseline until measured progressive disease (PD) or death from any cause, whichever is first. According to Response Evaluation Criteria in Solid Tumors v1.1 (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. | Baseline to Measured Progressive Disease or Death from Any Cause (Up to 21 Months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS was defined as time from baseline to 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. | Baseline to Death from Any Cause (Up to 28 Months) | 
| Percentage of Participants Who Achieved Best Overall Tumor Response of Complete Response (CR) or Partial Response (PR) [Objective Tumor Response Rate (ORR)] | Participants achieved an objective response if they had a best overall response of complete response (CR) or partial response (PR). According to RECIST v1.1, 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]); 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. The percentage of participants who achieved an objective response equals (number of participants with CR or PR)/(number of participants assessed)*100. | Baseline to Measured Progressive Disease or Participant Stops Study (Up to 97 Weeks) | 
| Percentage of Participants Who Achieved Best Overall Disease Response of CR, PR or Stable Disease (SD) [Disease Control Rate (DCR)] | Participants achieved disease control if they had a best overall response of PR, CR or SD. According to RECIST v1.1, 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]); 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. 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 equals (number of participants with CR, PR, or SD)/(number of participants assessed)*100. | Baseline to Measured Progressive Disease or Participant Stopped Study (Up to 97 Weeks) | 
| Change From Baseline in European Quality of Life Questionnaire - 5 Dimension (EQ-5D) Index Score | The EQ-5D is a quality-of-life instrument which 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). | Baseline, Day 21 Each Cycle (Cycle = 21 Days) and 30-Day Follow Up (Up to 97 Weeks) | 
| Change From Baseline in Lung Cancer Symptom Scale (LCSS) | The participant-reported LCSS was a 9-item questionnaire. Six items were symptom-specific measures for lung cancer (loss of appetite, fatigue, cough, dyspnea, hemoptysis, and pain), and 3 summation items described total symptomatic distress, interference with activity level, and global quality of life. Participant responses to each item were measured using a visual analog scale (VAS) from 0 (best outcome) to 100 (worst outcome). The Average Symptom Burden Index (ASBI) was the mean of the 6 symptom-specific items in the LCSS. The Total LCSS was the mean of all 9 LCSS items. 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. | Baseline to Measured Progressive Disease or Participant Stopped Study (up to 97 weeks) |