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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01703091
First received: October 5, 2012
Last updated: January 25, 2016
Last verified: January 2016
  Purpose
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.

Condition Intervention Phase
Non-small Cell Lung Cancer Metastatic
Drug: Ramucirumab
Drug: Placebo
Drug: Docetaxel
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Progression-Free Survival (PFS) [ Time Frame: Baseline to Measured Progressive Disease or Death from Any Cause (Up to 21 Months) ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Overall Survival (OS) [ Time Frame: Baseline to Death from Any Cause (Up to 28 Months) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    The LCSS assessed lung cancer-specific symptoms and their impact on quality of life. Each of the 9 symptoms was assessed on a 100 mm visual analog scale (VAS), with 0 representing no symptoms or better quality of life. For each participant, the maximum improvement over baseline score was calculated for each of the 9 LCSS items, Average Symptom Burden Index (ASBI), and Total LCSS. Negative values of change from baseline (i.e. decreases in the LCSS score towards the lower end of the symptom scale) indicated improvement in symptoms. For a participant and given LCSS item, if all change values were positive, the smallest positive change was the maximum improvement; if at least one change value was negative, the most negative value was the maximum improvement.


Enrollment: 197
Study Start Date: December 2012
Estimated Study Completion Date: August 2016
Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: Ramucirumab
Administered IV
Other Names:
  • LY 3009806
  • IMC-1121B
  • Cyramza®
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.
Drug: Placebo
Administered IV
Drug: Docetaxel
Administered IV

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01703091

Locations
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
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.
Fukuoka, Japan, 830-0011
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.
Hokkaido, Japan, 060-8648
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.
Hyogo, Japan, 673-8558
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.
Ishikawa, Japan, 920-8641
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.
Kanagawa, Japan, 236-0051
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.
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
Sponsors and Collaborators
Eli Lilly and Company
Investigators
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
  More Information

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01703091     History of Changes
Other Study ID Numbers: 14658  I4T-JE-JVCG 
Study First Received: October 5, 2012
Results First Received: December 14, 2015
Last Updated: January 25, 2016
Health Authority: Japan: Ministry of Health, Labor and Welfare
Japan: Pharmaceuticals and Medical Devices Agency

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Docetaxel
Antimitotic Agents
Antineoplastic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on April 27, 2016