A Study of Docetaxel and Ramucirumab Versus Docetaxel and Placebo in the Treatment of Stage IV Non-Small Cell Lung Cancer
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ClinicalTrials.gov Identifier: NCT01703091 |
Recruitment Status :
Completed
First Posted : October 10, 2012
Results First Posted : January 20, 2016
Last Update Posted : September 30, 2019
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Condition or disease | Intervention/treatment | Phase |
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Non-small Cell Lung Cancer Metastatic | Drug: Ramucirumab Drug: Placebo Drug: Docetaxel | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 197 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
Primary Purpose: | Treatment |
Official Title: | 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 |
Study Start Date : | December 2012 |
Actual Primary Completion Date : | December 2014 |
Actual Study Completion Date : | July 2016 |

Arm | Intervention/treatment |
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Experimental: Ramucirumab plus Docetaxel
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.
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Drug: Ramucirumab
Administered IV
Other Names:
Drug: Docetaxel Administered IV |
Placebo Comparator: Placebo plus Docetaxel
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.
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Drug: Placebo
Administered IV Drug: Docetaxel Administered IV |
- Progression-Free Survival (PFS) [ Time Frame: Baseline to Measured Progressive Disease or Death from Any Cause (Up to 21 Months) ]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.
- Overall Survival (OS) [ Time Frame: Baseline to Death from Any Cause (Up to 28 Months) ]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.
- Percentage of Participants Who Achieved Best Overall Tumor Response of Complete Response (CR) or Partial Response (PR) [Objective Tumor Response Rate (ORR)] [ Time Frame: Baseline to Measured Progressive Disease or Participant Stops Study (Up to 97 Weeks) ]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.
- Percentage of Participants Who Achieved Best Overall Disease Response of CR, PR or Stable Disease (SD) [Disease Control Rate (DCR)] [ Time Frame: Baseline to Measured Progressive Disease or Participant Stopped Study (Up to 97 Weeks) ]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.
- Change From Baseline in European Quality of Life Questionnaire - 5 Dimension (EQ-5D) Index Score [ Time Frame: Baseline, Day 21 Each Cycle (Cycle = 21 Days) and 30-Day Follow Up (Up to 97 Weeks) ]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).
- Change From Baseline in Lung Cancer Symptom Scale (LCSS) [ Time Frame: Baseline to Measured Progressive Disease or Participant Stopped Study (up to 97 weeks) ]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.

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Ages Eligible for Study: | 20 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01703091
Japan | |
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. | |
Aichi, Japan, 464-8681 | |
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. | |
Chiba, Japan, 277 8577 | |
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. | |
Ehime, Japan, 791-0280 | |
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Fukuoka, Japan, 830-0011 | |
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Hokkaido, Japan, 060-8648 | |
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Hyogo, Japan, 673-8558 | |
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Ishikawa, Japan, 920-8641 | |
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Kanagawa, Japan, 236-0051 | |
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Miyagi, Japan, 980-8574 | |
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. | |
Okayama, Japan, 700-8558 | |
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. | |
Osaka, Japan, 589-8511 | |
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. | |
Saitama, Japan, 362-0806 | |
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. | |
Shizuoka, Japan, 411-8777 | |
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. | |
Tokyo, Japan, 135-8550 | |
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. | |
Yamaguchi, Japan, 755-0241 |
Study Director: | Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) | Eli Lilly and Company |
Responsible Party: | Eli Lilly and Company |
ClinicalTrials.gov Identifier: | NCT01703091 |
Other Study ID Numbers: |
14658 I4T-JE-JVCG ( Other Identifier: Eli Lilly and Company ) |
First Posted: | October 10, 2012 Key Record Dates |
Results First Posted: | January 20, 2016 |
Last Update Posted: | September 30, 2019 |
Last Verified: | September 2019 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Yes |
Plan Description: | Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement. |
Time Frame: | Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting. |
Access Criteria: | A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement. |
URL: | https://vivli.org/ |
Lung Neoplasms Carcinoma, Non-Small-Cell Lung Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site Neoplasms Lung Diseases Respiratory Tract Diseases Carcinoma, Bronchogenic |
Bronchial Neoplasms Docetaxel Ramucirumab Antineoplastic Agents Tubulin Modulators Antimitotic Agents Mitosis Modulators Molecular Mechanisms of Pharmacological Action |