search
Back to results

A Study of Ramucirumab (LY3009806) in Combination With Erlotinib in Previously Untreated Participants With EGFR Mutation-Positive Metastatic NSCLC (RELAY) (RELAY)

Primary Purpose

Metastatic Non-Small Cell Lung Cancer

Status
Active
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Ramucirumab
Placebo
Erlotinib
Gefitinib
Osimertinib
Sponsored by
Eli Lilly and Company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Non-Small Cell Lung Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Cytologically or histologically confirmed diagnosis of Stage IV NSCLC as defined by the American Joint Committee on Cancer Staging Criteria for Lung Cancer (AJCC 7th edition 2009).
  • Eligible for first-line treatment with erlotinib based on documented evidence of tumor harboring an activating EGFR mutation [exon 19 deletion or exon 21 (L858R) substitution mutation].
  • Mandatory provision of adequate archived stage IV NSCLC tissue samples or tissue samples other than stage IV NSCLC may be acceptable (optional for part C).
  • At least one measurable lesion.
  • Life expectancy of at least 3 months.

Exclusion Criteria:

  • Known T790M EGFR mutation (not applicable for Part C Period 2).
  • Known leptomeningeal carcinomatosis, uncontrolled/unstable spinal cord compression, or brain metastases.
  • Serious illness or medical condition.
  • Ongoing treatment with CYP3A4 inducers or strong inhibitors.
  • Ongoing therapy with nonsteroidal anti-inflammatory drugs for more than 2 months.
  • History of gross hemoptysis.
  • Significant bleeding disorders.
  • Radiologically documented evidence of major blood vessel invasion or encasement by cancer.
  • Radiographic evidence of intratumor cavitation.
  • History of gastrointestinal perforation within last 6 months.
  • History of bowel obstruction, inflammatory enteropathy or extensive intestinal resection.
  • History of any arterial thrombotic event within 6 months prior to enrollment.
  • The participant has any known significant ophthalmologic abnormalities of the surface of the eye.

Sites / Locations

  • TRIO - Translational Research in Oncology-US, Inc.
  • UCLA Medical Center
  • Pharmatech Oncology Inc
  • The Queen's Medical Center
  • Cancer Center of Kansas
  • Queens Medical Associates
  • Levine Cancer Institute- Carolinas Medical Center
  • St. Charles Health System
  • Allegheny General Hospital
  • Cross Cancer Institute
  • CHU Albert Michallon
  • CHRU de Lille-Hôpital Albert Calmette
  • Centre hospitalier universitaire Lapeyronie
  • APHP-Hôpital Européen Georges Pompidou
  • CHU la Miletrie
  • Klinik Schillerhöhe
  • Thoraxklinik Heidelberg gGmbH
  • Kliniken der Stadt Köln gGmbH Klinikum Köln-Merheim
  • Städtisches Krankenhaus Martha-Maria Halle-Dölau gGmbH
  • Klinikum Chemnitz GmbH
  • LungenClinic Grosshansdorf
  • HELIOS Klinikum Emil von Behring
  • University General Hospital of Patras
  • SOTIRIA General Hospital
  • Queen Mary Hospital
  • Queen Elizabeth Hospital
  • Azienda per l'Assistenza Sanitaria n°5 "Friuli Occidentale"
  • Azienda Ospedaliero - Universitaria S. Luigi Gonzaga
  • IRCCS Ospedale Oncologico di Bari
  • Policlinico S. Orsola Malpighi - Universita di Bologna
  • IRCCS Ospedale San Raffaele
  • Istituto Oncologico Veneto
  • Nagoya Medical Center
  • Aichi Cancer Center Hospital
  • National Cancer Center Hospital East
  • National Hospital Organization Shikoku Cancer Center
  • Kurume University Hospital
  • National Hospital Organization Asahikawa Medical Center
  • Hyogo Cancer Center
  • Hyogo Prefectual Amagasaki General Medical Center
  • National Hospital Organization Himeji Medical Center
  • Foundation for Biomedical Research and innovation
  • Kobe City Medical Center General Hospital
  • Kanazawa University Hospital
  • Kanagawa Cardiovascular and Respiratory Center
  • Kanagawa Cancer Center
  • Sendai Kousei Hospital
  • Osaka Habikino Medical Center
  • Kansai Medical University Hospital
  • Kishiwada City Hospital
  • Kindai University Hospital
  • National Hospital Organization Kinki-Chuo Chest Medical Cent
  • Saitama Cancer Center
  • Shizuoka Cancer Center
  • Juntendo University Hospital
  • Nippon Medical School Hospital
  • Tokyo Met Cancer & Infectious Diseases Center Komagome Hp
  • National Cancer Center Hospital
  • St. Lukes International Hospital
  • The Cancer Institute Hospital of JFCR
  • Yamaguchi-Ube Medical Center
  • Chiba University Hospital
  • National Hospital Organization Kyushu Medical Center
  • Kyushu Cancer Center
  • Kyushu University Hospital
  • Kyoto University Hospital
  • Nagasaki University Hospital
  • Niigata University Medical & Dental Hospital
  • Niigata Cancer Center Hospital
  • Okayama University Hospital
  • Osaka City General Hospital
  • Osaka International Cancer Institute
  • Osaka City University Hospital
  • Wakayama MedicaL University Hospital
  • Chungbuk National University Hospital
  • Saint Vincent Hospital
  • Ajou University Hospital
  • Gyeong-Sang National University Hospital
  • Samsung Medical Center
  • Korea University Guro Hospital
  • Ulsan University Hospital
  • Asan Medical Center
  • Seoul St. Mary's Hospital
  • Seoul Municipal Boramae Hospital
  • S.C. MedisProf SRL
  • Institutul Oncologic Dr Trestioreanu Bucuresti
  • Hospital Fundacion Son Llatzer
  • Institut Catala d'Oncologia
  • Hospital Universitario Quiron Madrid
  • Clinica Universitaria De Navarra
  • Hospital Universitari Vall d'Hebron
  • Hospital Universitario 12 de Octubre
  • Hospital Universitario Virgen del Rocio
  • Hospital Universitario Nuestra Señora de Valme
  • Hospital Universitario La Fe de Valencia
  • Chang Gung Memorial Hospital - Kaohsiung
  • E-DA Hospital
  • China Medical University Hospital
  • Taichung Veterans General Hospital
  • National Cheng Kung University Hospital
  • National Taiwan University Hospital
  • MacKay Memorial Hospital
  • Taipei Veterans General Hospital
  • Baskent Adana Educational Hospital
  • Trakya University Faculty of Medicine
  • Ege University Faculty of Medicine
  • Inonu University Medical Faculty
  • Royal Marsden NHS Trust
  • Charing Cross Hospital
  • Nottingham City Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Experimental

Arm Label

Ramucirumab + Erlotinib

Placebo + Erlotinib

Ramucirumab + Gefitinib or Osimertinib

Arm Description

Part A: 10 milligrams per kilogram (mg/kg) ramucirumab administered every 2 weeks intravenously (IV) in combination with 150 mg erlotinib daily orally. Participants may continue to receive treatment until discontinuation criteria are met. Part B: 10 mg/kg ramucirumab administered every 2 weeks IV in combination with 150 mg erlotinib daily orally. Participants may continue to receive treatment until discontinuation criteria are met.

Part B: Placebo administered every 2 weeks IV in combination with 150 mg erlotinib daily orally. Participants may continue to receive treatment until discontinuation criteria are met.

Part C: 10 mg/kg ramucirumab administered every 2 weeks intravenously (IV) + 250 mg Gefitinib or 80 mg Osimertinib daily orally. Ramucirumab and gefitinib administered during period 1. Ramucirumab and osimertinib administered during period 2.

Outcomes

Primary Outcome Measures

Part B: Progression Free Survival (PFS)
PFS is defined as the time from the date of randomization to the date of radiographically documented progressive disease (PD) based on investigator assessment, or the date of death due to any cause, whichever is first assessed via Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Progressive Disease (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 relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of 1 or more new lesions is also considered progression.
Number of Participants With Treatment-Emergent Adverse Events
A summary of other non-serious adverse events and all serious adverse events, regardless of causality, is located in the Reported Adverse Events Section.

Secondary Outcome Measures

Part B: Overall Survival (OS)
OS was defined as the time from the date of randomization to the date of death from any cause. For each participant who was not known to have died as of the data-inclusion cutoff date for a particular analysis,OS was censored for that analysis at the date of last contact prior to the data-inclusion cutoff date (contacts considered in the determination of last contact date include adverse event (AE) date, lesion assessment date, visit date, and last known alive date).
Part B: Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])
ORR was defined as the percentage of randomized participants achieving a best overall response of partial response (PR) or complete response (CR) assessed via Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR was defined as the disappearance of all lesions, pathological lymph node reduction in short axis to <10 mm, and normalization of tumor marker levels of non-target lesions. PR was at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters. Progressive Disease (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 relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of 1 or more new lesions is also considered progression.
Part B: Percentage of Participants With CR, PR, or Stable Disease (SD) (Disease Control Rate [DCR])
DCR was defined as the percentage of randomized participants achieving a best overall response of CR,PR, or stable disease(SD) assessed via Response Evaluation Criteria in Solid Tumors(RECIST) version 1.1. CR was defined as the disappearance of all lesions,pathological lymph node reduction in short axis to <10 mm, and normalization of tumor marker levels of non-target lesions.PR was at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters.SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Progressive Disease(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 relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.The appearance of 1 or more new lesions is also considered progression.
Part B: Duration of Response (DoR)
DoR was defined as the date of first documented CR or PR (responder) to the date of progressive disease or the date of death due to any cause, whichever was earlier. If a responder was not known to have died or have progressive disease, then the participant was censored at the date of last evaluable tumor assessment.CR was defined as the disappearance of all lesions, pathological lymph node reduction in short axis to <10 mm, and normalization of tumor marker levels of non-target lesions. PR was at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters. Progressive Disease (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 relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of 1 or more new lesions is also considered progression.
Part B: Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab
Part B: Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab
Part B: Number of Participants With Anti-Ramucirumab Antibodies
Part B: Number of Participants With Anti-Ramucirumab Antibodies.
Part B: Best Change From Baseline on the 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 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-millimeter (mm) lines. A higher score for any item represented a higher level of symptoms/problems. The LCSS total score was defined as the mean of all 9 items. Average symptom burden index (ASBI) was calculated as the mean of the six symptom-specific questions from the LCSS. Potential scores range from 0 (for best outcome) to 100 (for worst outcome).
Part B: Change From Baseline on the EuroQol 5-Dimension, 5-Level Questionnaire (EQ-5D-5L) Index Score
The EQ-5D-5L is a standardized instrument used to measure self-reported health status of the participants. It consists of 5 health dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). There are 5 response levels (no problems, slight problems, moderate problems, severe problems, and extreme problems/unable to), ranging from 1 to 5 (good to bad). Dimension responses were converted to an index score using UK weights. The index scores were anchored on full health (1.0) to dead (0) with negative values assigned to health states considered worse than death.
Part B: Change From Baseline on the EuroQol 5-Dimension, 5-Level Questionnaire (EQ-5D-5L) Index Score
The EQ-5D-5L is a standardized instrument used to measure self-reported health status of the participants. It consists of 5 health dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). There are 5 response levels (no problems, slight problems, moderate problems, severe problems, and extreme problems/unable to), ranging from 1 to 5 (good to bad). Dimension responses were converted to an index score using UK weights. The index scores were anchored on full health (1.0) to dead (0) with negative values assigned to health states considered worse than death.
Part B: Change From Baseline on the EuroQol 5-Dimension, 5-Level Questionnaire (EQ-5D-5L) Index Score
The EQ-5D-5L is a standardized instrument used to measure self-reported health status of the participants. It consists of 5 health dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). There are 5 response levels (no problems, slight problems, moderate problems, severe problems, and extreme problems/unable to), ranging from 1 to 5 (good to bad). Dimension responses were converted to an index score using UK weights. The index scores were anchored on full health (1.0) to dead (0) with negative values assigned to health states considered worse than death.

Full Information

First Posted
April 3, 2015
Last Updated
May 31, 2023
Sponsor
Eli Lilly and Company
search

1. Study Identification

Unique Protocol Identification Number
NCT02411448
Brief Title
A Study of Ramucirumab (LY3009806) in Combination With Erlotinib in Previously Untreated Participants With EGFR Mutation-Positive Metastatic NSCLC (RELAY)
Acronym
RELAY
Official Title
A Multicenter, Randomized, Double-Blind Study of Erlotinib in Combination With Ramucirumab or Placebo in Previously Untreated Patients With EGFR Mutation-Positive Metastatic Non-Small Cell Lung Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
May 6, 2015 (Actual)
Primary Completion Date
January 23, 2019 (Actual)
Study Completion Date
December 16, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eli Lilly and Company

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The main purpose of this study is to evaluate the efficacy and safety of ramucirumab in combination with erlotinib as compared to placebo in combination with erlotinib in previously untreated participants with stage IV non-small cell lung cancer (NSCLC) harboring an activating epidermal growth factor receptor (EGFR) mutation (Exon 19-Del and Exon 21 L858R). Safety and tolerability of ramucirumab in combination with erlotinib will be assessed in Part A before proceeding to Part B. The purpose of Part C is to determine the efficacy and safety of ramucirumab in combination with gefitinib in previously untreated East Asian participants with EGFR mutation-positive metastatic NSCLC and of ramucirumab in combination with osimertinib in those participants whose disease progressed on ramucirumab and gefitinib and that have T790M - positive metastatic NSCLC.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Non-Small Cell Lung Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
545 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Ramucirumab + Erlotinib
Arm Type
Experimental
Arm Description
Part A: 10 milligrams per kilogram (mg/kg) ramucirumab administered every 2 weeks intravenously (IV) in combination with 150 mg erlotinib daily orally. Participants may continue to receive treatment until discontinuation criteria are met. Part B: 10 mg/kg ramucirumab administered every 2 weeks IV in combination with 150 mg erlotinib daily orally. Participants may continue to receive treatment until discontinuation criteria are met.
Arm Title
Placebo + Erlotinib
Arm Type
Placebo Comparator
Arm Description
Part B: Placebo administered every 2 weeks IV in combination with 150 mg erlotinib daily orally. Participants may continue to receive treatment until discontinuation criteria are met.
Arm Title
Ramucirumab + Gefitinib or Osimertinib
Arm Type
Experimental
Arm Description
Part C: 10 mg/kg ramucirumab administered every 2 weeks intravenously (IV) + 250 mg Gefitinib or 80 mg Osimertinib daily orally. Ramucirumab and gefitinib administered during period 1. Ramucirumab and osimertinib administered during period 2.
Intervention Type
Drug
Intervention Name(s)
Ramucirumab
Other Intervention Name(s)
LY3009806
Intervention Description
Administered IV.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Administered IV.
Intervention Type
Drug
Intervention Name(s)
Erlotinib
Intervention Description
Administered orally.
Intervention Type
Drug
Intervention Name(s)
Gefitinib
Intervention Description
Administered orally.
Intervention Type
Drug
Intervention Name(s)
Osimertinib
Intervention Description
Administered orally.
Primary Outcome Measure Information:
Title
Part B: Progression Free Survival (PFS)
Description
PFS is defined as the time from the date of randomization to the date of radiographically documented progressive disease (PD) based on investigator assessment, or the date of death due to any cause, whichever is first assessed via Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Progressive Disease (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 relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of 1 or more new lesions is also considered progression.
Time Frame
Randomization to Measured Progressive Disease or Death from Any Cause (Up To 37 Months)
Title
Number of Participants With Treatment-Emergent Adverse Events
Description
A summary of other non-serious adverse events and all serious adverse events, regardless of causality, is located in the Reported Adverse Events Section.
Time Frame
Cycle 1 Day 1 through End of Study (Up To 3 Years)
Secondary Outcome Measure Information:
Title
Part B: Overall Survival (OS)
Description
OS was defined as the time from the date of randomization to the date of death from any cause. For each participant who was not known to have died as of the data-inclusion cutoff date for a particular analysis,OS was censored for that analysis at the date of last contact prior to the data-inclusion cutoff date (contacts considered in the determination of last contact date include adverse event (AE) date, lesion assessment date, visit date, and last known alive date).
Time Frame
Randomization to Date of Death from Any Cause (Up To 37 Months)
Title
Part B: Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])
Description
ORR was defined as the percentage of randomized participants achieving a best overall response of partial response (PR) or complete response (CR) assessed via Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR was defined as the disappearance of all lesions, pathological lymph node reduction in short axis to <10 mm, and normalization of tumor marker levels of non-target lesions. PR was at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters. Progressive Disease (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 relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of 1 or more new lesions is also considered progression.
Time Frame
Randomization to Progressive Disease (Up To 37 Months)
Title
Part B: Percentage of Participants With CR, PR, or Stable Disease (SD) (Disease Control Rate [DCR])
Description
DCR was defined as the percentage of randomized participants achieving a best overall response of CR,PR, or stable disease(SD) assessed via Response Evaluation Criteria in Solid Tumors(RECIST) version 1.1. CR was defined as the disappearance of all lesions,pathological lymph node reduction in short axis to <10 mm, and normalization of tumor marker levels of non-target lesions.PR was at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters.SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Progressive Disease(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 relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.The appearance of 1 or more new lesions is also considered progression.
Time Frame
Randomization to Progressive Disease (Up To 37 Months)
Title
Part B: Duration of Response (DoR)
Description
DoR was defined as the date of first documented CR or PR (responder) to the date of progressive disease or the date of death due to any cause, whichever was earlier. If a responder was not known to have died or have progressive disease, then the participant was censored at the date of last evaluable tumor assessment.CR was defined as the disappearance of all lesions, pathological lymph node reduction in short axis to <10 mm, and normalization of tumor marker levels of non-target lesions. PR was at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters. Progressive Disease (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 relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of 1 or more new lesions is also considered progression.
Time Frame
Date of Complete Response (CR) or Partial Response (PR) to Date of Objective Disease Progression or Death Due to Any Cause (Up To 37 Months)
Title
Part B: Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab
Description
Part B: Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab
Time Frame
Cycle 2 Day 1: Predose; Cycle 4 Day 1: Predose; Cycle 7 Day 1: Predose; Cycle 14 Day 1
Title
Part B: Number of Participants With Anti-Ramucirumab Antibodies
Description
Part B: Number of Participants With Anti-Ramucirumab Antibodies.
Time Frame
Cycle 1 Predose through Follow-up (Up To 37 Months)
Title
Part B: Best Change From Baseline on the Lung Cancer Symptom Scale (LCSS)
Description
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 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-millimeter (mm) lines. A higher score for any item represented a higher level of symptoms/problems. The LCSS total score was defined as the mean of all 9 items. Average symptom burden index (ASBI) was calculated as the mean of the six symptom-specific questions from the LCSS. Potential scores range from 0 (for best outcome) to 100 (for worst outcome).
Time Frame
Baseline, End of Study (Up To 37 Months)
Title
Part B: Change From Baseline on the EuroQol 5-Dimension, 5-Level Questionnaire (EQ-5D-5L) Index Score
Description
The EQ-5D-5L is a standardized instrument used to measure self-reported health status of the participants. It consists of 5 health dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). There are 5 response levels (no problems, slight problems, moderate problems, severe problems, and extreme problems/unable to), ranging from 1 to 5 (good to bad). Dimension responses were converted to an index score using UK weights. The index scores were anchored on full health (1.0) to dead (0) with negative values assigned to health states considered worse than death.
Time Frame
Baseline, Cycle 10 (each cycle is 2 weeks)
Title
Part B: Change From Baseline on the EuroQol 5-Dimension, 5-Level Questionnaire (EQ-5D-5L) Index Score
Description
The EQ-5D-5L is a standardized instrument used to measure self-reported health status of the participants. It consists of 5 health dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). There are 5 response levels (no problems, slight problems, moderate problems, severe problems, and extreme problems/unable to), ranging from 1 to 5 (good to bad). Dimension responses were converted to an index score using UK weights. The index scores were anchored on full health (1.0) to dead (0) with negative values assigned to health states considered worse than death.
Time Frame
Baseline, Cycle 28 (each cycle is 2 weeks)
Title
Part B: Change From Baseline on the EuroQol 5-Dimension, 5-Level Questionnaire (EQ-5D-5L) Index Score
Description
The EQ-5D-5L is a standardized instrument used to measure self-reported health status of the participants. It consists of 5 health dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). There are 5 response levels (no problems, slight problems, moderate problems, severe problems, and extreme problems/unable to), ranging from 1 to 5 (good to bad). Dimension responses were converted to an index score using UK weights. The index scores were anchored on full health (1.0) to dead (0) with negative values assigned to health states considered worse than death.
Time Frame
Baseline, Cycle 40 (each cycle is 2 weeks)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Cytologically or histologically confirmed diagnosis of Stage IV NSCLC as defined by the American Joint Committee on Cancer Staging Criteria for Lung Cancer (AJCC 7th edition 2009). Eligible for first-line treatment with erlotinib based on documented evidence of tumor harboring an activating EGFR mutation [exon 19 deletion or exon 21 (L858R) substitution mutation]. Mandatory provision of adequate archived stage IV NSCLC tissue samples or tissue samples other than stage IV NSCLC may be acceptable (optional for part C). At least one measurable lesion. Life expectancy of at least 3 months. Exclusion Criteria: Known T790M EGFR mutation (not applicable for Part C Period 2). Known leptomeningeal carcinomatosis, uncontrolled/unstable spinal cord compression, or brain metastases. Serious illness or medical condition. Ongoing treatment with CYP3A4 inducers or strong inhibitors. Ongoing therapy with nonsteroidal anti-inflammatory drugs for more than 2 months. History of gross hemoptysis. Significant bleeding disorders. Radiologically documented evidence of major blood vessel invasion or encasement by cancer. Radiographic evidence of intratumor cavitation. History of gastrointestinal perforation within last 6 months. History of bowel obstruction, inflammatory enteropathy or extensive intestinal resection. History of any arterial thrombotic event within 6 months prior to enrollment. The participant has any known significant ophthalmologic abnormalities of the surface of the eye.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
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)
Organizational Affiliation
Eli Lilly and Company
Official's Role
Study Director
Facility Information:
Facility Name
TRIO - Translational Research in Oncology-US, Inc.
City
Los Angeles
State/Province
California
ZIP/Postal Code
90024
Country
United States
Facility Name
UCLA Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Pharmatech Oncology Inc
City
Denver
State/Province
Colorado
ZIP/Postal Code
80203
Country
United States
Facility Name
The Queen's Medical Center
City
Honolulu
State/Province
Hawaii
ZIP/Postal Code
96813
Country
United States
Facility Name
Cancer Center of Kansas
City
Wichita
State/Province
Kansas
ZIP/Postal Code
67214
Country
United States
Facility Name
Queens Medical Associates
City
Fresh Meadows
State/Province
New York
ZIP/Postal Code
11366
Country
United States
Facility Name
Levine Cancer Institute- Carolinas Medical Center
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28204
Country
United States
Facility Name
St. Charles Health System
City
Bend
State/Province
Oregon
ZIP/Postal Code
97701
Country
United States
Facility Name
Allegheny General Hospital
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15212
Country
United States
Facility Name
Cross Cancer Institute
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 1Z2
Country
Canada
Facility Name
CHU Albert Michallon
City
Grenoble
State/Province
Cedex 9
ZIP/Postal Code
38049
Country
France
Facility Name
CHRU de Lille-Hôpital Albert Calmette
City
Lille
ZIP/Postal Code
59037
Country
France
Facility Name
Centre hospitalier universitaire Lapeyronie
City
Montpellier Cedex 5
ZIP/Postal Code
34295
Country
France
Facility Name
APHP-Hôpital Européen Georges Pompidou
City
Paris
ZIP/Postal Code
75015
Country
France
Facility Name
CHU la Miletrie
City
Poitiers
ZIP/Postal Code
86021
Country
France
Facility Name
Klinik Schillerhöhe
City
Gerlingen
State/Province
Baden-Württemberg
ZIP/Postal Code
70839
Country
Germany
Facility Name
Thoraxklinik Heidelberg gGmbH
City
Heidelberg
State/Province
Baden-Württemberg
ZIP/Postal Code
69126
Country
Germany
Facility Name
Kliniken der Stadt Köln gGmbH Klinikum Köln-Merheim
City
Köln
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
51109
Country
Germany
Facility Name
Städtisches Krankenhaus Martha-Maria Halle-Dölau gGmbH
City
Halle (Saale)
State/Province
Sachsen-Anhalt
ZIP/Postal Code
06120
Country
Germany
Facility Name
Klinikum Chemnitz GmbH
City
Chemnitz
State/Province
Sachsen
ZIP/Postal Code
09113
Country
Germany
Facility Name
LungenClinic Grosshansdorf
City
Großhansdorf
State/Province
Schleswig-Holstein
ZIP/Postal Code
22927
Country
Germany
Facility Name
HELIOS Klinikum Emil von Behring
City
Berlin
ZIP/Postal Code
14165
Country
Germany
Facility Name
University General Hospital of Patras
City
Patras
State/Province
Achaia
ZIP/Postal Code
26504
Country
Greece
Facility Name
SOTIRIA General Hospital
City
Athens
ZIP/Postal Code
11527
Country
Greece
Facility Name
Queen Mary Hospital
City
Hong Kong
Country
Hong Kong
Facility Name
Queen Elizabeth Hospital
City
Kowloon
Country
Hong Kong
Facility Name
Azienda per l'Assistenza Sanitaria n°5 "Friuli Occidentale"
City
Pordenone
State/Province
PD
ZIP/Postal Code
33170
Country
Italy
Facility Name
Azienda Ospedaliero - Universitaria S. Luigi Gonzaga
City
Orbassano
State/Province
Torino
ZIP/Postal Code
10043
Country
Italy
Facility Name
IRCCS Ospedale Oncologico di Bari
City
Bari
ZIP/Postal Code
70124
Country
Italy
Facility Name
Policlinico S. Orsola Malpighi - Universita di Bologna
City
Bologna
ZIP/Postal Code
40138
Country
Italy
Facility Name
IRCCS Ospedale San Raffaele
City
Milano
ZIP/Postal Code
20132
Country
Italy
Facility Name
Istituto Oncologico Veneto
City
Padova
ZIP/Postal Code
35128
Country
Italy
Facility Name
Nagoya Medical Center
City
Nagoya
State/Province
Aichi
ZIP/Postal Code
460-0001
Country
Japan
Facility Name
Aichi Cancer Center Hospital
City
Nagoya
State/Province
Aichi
ZIP/Postal Code
464-8681
Country
Japan
Facility Name
National Cancer Center Hospital East
City
Kashiwa
State/Province
Chiba
ZIP/Postal Code
277 8577
Country
Japan
Facility Name
National Hospital Organization Shikoku Cancer Center
City
Matsuyama
State/Province
Ehime
ZIP/Postal Code
791-0280
Country
Japan
Facility Name
Kurume University Hospital
City
Kurume
State/Province
Fukuoka
ZIP/Postal Code
830-0011
Country
Japan
Facility Name
National Hospital Organization Asahikawa Medical Center
City
Asahikawa
State/Province
Hokkaido
ZIP/Postal Code
070-8644
Country
Japan
Facility Name
Hyogo Cancer Center
City
Akashi
State/Province
Hyogo
ZIP/Postal Code
673-8558
Country
Japan
Facility Name
Hyogo Prefectual Amagasaki General Medical Center
City
Amagashiki City
State/Province
Hyogo
ZIP/Postal Code
6608550
Country
Japan
Facility Name
National Hospital Organization Himeji Medical Center
City
Himeji
State/Province
Hyogo
ZIP/Postal Code
670-8520
Country
Japan
Facility Name
Foundation for Biomedical Research and innovation
City
Kobe
State/Province
Hyogo
ZIP/Postal Code
650-0047
Country
Japan
Facility Name
Kobe City Medical Center General Hospital
City
Kobe
State/Province
Hyogo
ZIP/Postal Code
650-0047
Country
Japan
Facility Name
Kanazawa University Hospital
City
Kanazawa
State/Province
Ishikawa
ZIP/Postal Code
920-8641
Country
Japan
Facility Name
Kanagawa Cardiovascular and Respiratory Center
City
Yokohama
State/Province
Kanagawa
ZIP/Postal Code
236-0051
Country
Japan
Facility Name
Kanagawa Cancer Center
City
Yokohama
State/Province
Kanagawa
ZIP/Postal Code
241-8515
Country
Japan
Facility Name
Sendai Kousei Hospital
City
Sendai
State/Province
Miyagi
ZIP/Postal Code
980-0873
Country
Japan
Facility Name
Osaka Habikino Medical Center
City
Habikino
State/Province
Osaka
ZIP/Postal Code
583-8588
Country
Japan
Facility Name
Kansai Medical University Hospital
City
Hirakata
State/Province
Osaka
ZIP/Postal Code
573-1191
Country
Japan
Facility Name
Kishiwada City Hospital
City
Kishiwada
State/Province
Osaka
ZIP/Postal Code
596-8501
Country
Japan
Facility Name
Kindai University Hospital
City
Osaka Sayama-shi
State/Province
Osaka
ZIP/Postal Code
589 8511
Country
Japan
Facility Name
National Hospital Organization Kinki-Chuo Chest Medical Cent
City
Sakai
State/Province
Osaka
ZIP/Postal Code
5918555
Country
Japan
Facility Name
Saitama Cancer Center
City
Kita-Adachi
State/Province
Saitama
ZIP/Postal Code
362-0806
Country
Japan
Facility Name
Shizuoka Cancer Center
City
Sunto-Gun
State/Province
Shizuoka
ZIP/Postal Code
411-8777
Country
Japan
Facility Name
Juntendo University Hospital
City
Bunkyo-ku
State/Province
Tokyo
ZIP/Postal Code
113-8431
Country
Japan
Facility Name
Nippon Medical School Hospital
City
Bunkyo-Ku
State/Province
Tokyo
ZIP/Postal Code
113-8603
Country
Japan
Facility Name
Tokyo Met Cancer & Infectious Diseases Center Komagome Hp
City
Bunkyo-ku
State/Province
Tokyo
ZIP/Postal Code
113-8677
Country
Japan
Facility Name
National Cancer Center Hospital
City
Chuo-Ku
State/Province
Tokyo
ZIP/Postal Code
104-0045
Country
Japan
Facility Name
St. Lukes International Hospital
City
Chuo-Ku
State/Province
Tokyo
ZIP/Postal Code
104-8560
Country
Japan
Facility Name
The Cancer Institute Hospital of JFCR
City
Koto-ku
State/Province
Tokyo
ZIP/Postal Code
135-8550
Country
Japan
Facility Name
Yamaguchi-Ube Medical Center
City
Ube
State/Province
Yamaguchi
ZIP/Postal Code
755-0241
Country
Japan
Facility Name
Chiba University Hospital
City
Chiba
ZIP/Postal Code
260-8677
Country
Japan
Facility Name
National Hospital Organization Kyushu Medical Center
City
Fukuoka
ZIP/Postal Code
810-8563
Country
Japan
Facility Name
Kyushu Cancer Center
City
Fukuoka
ZIP/Postal Code
811-1395
Country
Japan
Facility Name
Kyushu University Hospital
City
Fukuoka
ZIP/Postal Code
812-8582
Country
Japan
Facility Name
Kyoto University Hospital
City
Kyoto
ZIP/Postal Code
606-8507
Country
Japan
Facility Name
Nagasaki University Hospital
City
Nagasaki
ZIP/Postal Code
852-8501
Country
Japan
Facility Name
Niigata University Medical & Dental Hospital
City
Niigata
ZIP/Postal Code
951-8520
Country
Japan
Facility Name
Niigata Cancer Center Hospital
City
Niigata
ZIP/Postal Code
951-8566
Country
Japan
Facility Name
Okayama University Hospital
City
Okayama
ZIP/Postal Code
700-8558
Country
Japan
Facility Name
Osaka City General Hospital
City
Osaka
ZIP/Postal Code
534-0021
Country
Japan
Facility Name
Osaka International Cancer Institute
City
Osaka
ZIP/Postal Code
541-8567
Country
Japan
Facility Name
Osaka City University Hospital
City
Osaka
ZIP/Postal Code
545-8586
Country
Japan
Facility Name
Wakayama MedicaL University Hospital
City
Wakayama
ZIP/Postal Code
641-8510
Country
Japan
Facility Name
Chungbuk National University Hospital
City
Cheongju-si
State/Province
Chungcheongbuk-do
ZIP/Postal Code
28644
Country
Korea, Republic of
Facility Name
Saint Vincent Hospital
City
Suwon
State/Province
Gyeonggi-do
ZIP/Postal Code
16247
Country
Korea, Republic of
Facility Name
Ajou University Hospital
City
Suwon
State/Province
Gyeonggi-do
ZIP/Postal Code
16499
Country
Korea, Republic of
Facility Name
Gyeong-Sang National University Hospital
City
Jin-ju-si
State/Province
Gyeongsangnam-do
ZIP/Postal Code
52727
Country
Korea, Republic of
Facility Name
Samsung Medical Center
City
Seoul
State/Province
Korea
ZIP/Postal Code
06351
Country
Korea, Republic of
Facility Name
Korea University Guro Hospital
City
Seoul
State/Province
Korea
ZIP/Postal Code
08308
Country
Korea, Republic of
Facility Name
Ulsan University Hospital
City
Ulsan
State/Province
Korea
ZIP/Postal Code
44033
Country
Korea, Republic of
Facility Name
Asan Medical Center
City
Songpa-gu
State/Province
Seoul
ZIP/Postal Code
05505
Country
Korea, Republic of
Facility Name
Seoul St. Mary's Hospital
City
Seoul
ZIP/Postal Code
06591
Country
Korea, Republic of
Facility Name
Seoul Municipal Boramae Hospital
City
Seoul
ZIP/Postal Code
07061
Country
Korea, Republic of
Facility Name
S.C. MedisProf SRL
City
Cluj-Napoca
State/Province
Cluj
ZIP/Postal Code
400058
Country
Romania
Facility Name
Institutul Oncologic Dr Trestioreanu Bucuresti
City
Bucuresti
State/Province
Sector 2
ZIP/Postal Code
022328
Country
Romania
Facility Name
Hospital Fundacion Son Llatzer
City
Palma de Mallorca
State/Province
Baleares
ZIP/Postal Code
07198
Country
Spain
Facility Name
Institut Catala d'Oncologia
City
L'Hospitalet de Llobregat
State/Province
Barcelona
ZIP/Postal Code
08907
Country
Spain
Facility Name
Hospital Universitario Quiron Madrid
City
Pozuelo de Alarcon
State/Province
Madrid
ZIP/Postal Code
28223
Country
Spain
Facility Name
Clinica Universitaria De Navarra
City
Pamplona
State/Province
Navarra
ZIP/Postal Code
31008
Country
Spain
Facility Name
Hospital Universitari Vall d'Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Universitario 12 de Octubre
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Facility Name
Hospital Universitario Virgen del Rocio
City
Sevilla
ZIP/Postal Code
41013
Country
Spain
Facility Name
Hospital Universitario Nuestra Señora de Valme
City
Sevilla
ZIP/Postal Code
46014
Country
Spain
Facility Name
Hospital Universitario La Fe de Valencia
City
Valencia
ZIP/Postal Code
46026
Country
Spain
Facility Name
Chang Gung Memorial Hospital - Kaohsiung
City
Kaohsiung City
ZIP/Postal Code
83301
Country
Taiwan
Facility Name
E-DA Hospital
City
Kaohsiung
ZIP/Postal Code
82445
Country
Taiwan
Facility Name
China Medical University Hospital
City
Taichung City
ZIP/Postal Code
40447
Country
Taiwan
Facility Name
Taichung Veterans General Hospital
City
Taichung
ZIP/Postal Code
40705
Country
Taiwan
Facility Name
National Cheng Kung University Hospital
City
Tainan
ZIP/Postal Code
704
Country
Taiwan
Facility Name
National Taiwan University Hospital
City
Taipei City
ZIP/Postal Code
10048
Country
Taiwan
Facility Name
MacKay Memorial Hospital
City
Taipei City
ZIP/Postal Code
10449
Country
Taiwan
Facility Name
Taipei Veterans General Hospital
City
Taipei
ZIP/Postal Code
11217
Country
Taiwan
Facility Name
Baskent Adana Educational Hospital
City
Adana
ZIP/Postal Code
1250
Country
Turkey
Facility Name
Trakya University Faculty of Medicine
City
Edirne
ZIP/Postal Code
22770
Country
Turkey
Facility Name
Ege University Faculty of Medicine
City
Izmir
ZIP/Postal Code
35100
Country
Turkey
Facility Name
Inonu University Medical Faculty
City
Malatya
ZIP/Postal Code
44280
Country
Turkey
Facility Name
Royal Marsden NHS Trust
City
London
State/Province
Greater London
ZIP/Postal Code
SW3 6JJ
Country
United Kingdom
Facility Name
Charing Cross Hospital
City
Chelsea
State/Province
London
ZIP/Postal Code
W6 8RF
Country
United Kingdom
Facility Name
Nottingham City Hospital
City
Nottingham
State/Province
Nottinghamshire
ZIP/Postal Code
NG5 1PB
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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.
IPD Sharing 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.
IPD Sharing Access Criteria
A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
IPD Sharing URL
https://vivli.org/
Citations:
PubMed Identifier
35841410
Citation
Nakagawa K, Garon EB, Gao L, Callies S, Zimmermann A, Walgren R, Visseren-Grul C, Reck M. RELAY, ramucirumab plus erlotinib versus placebo plus erlotinib in untreated EGFR-mutated metastatic non-small cell lung cancer: exposure-response relationship. Cancer Chemother Pharmacol. 2022 Aug;90(2):137-148. doi: 10.1007/s00280-022-04447-x. Epub 2022 Jul 16.
Results Reference
derived
PubMed Identifier
35369607
Citation
Nishio M, Nishio K, Reck M, Garon EB, Imamura F, Kawaguchi T, Yamaguchi H, Ikeda S, Hirano K, Visseren-Grul C, Ceccarelli M, Wijayawardana SR, Zimmermann A, Matsui T, Enatsu S, Nakagawa K. RELAY+: Exploratory Study of Ramucirumab Plus Gefitinib in Untreated Patients With EGFR-Mutated Metastatic NSCLC. JTO Clin Res Rep. 2022 Feb 26;3(4):100303. doi: 10.1016/j.jtocrr.2022.100303. eCollection 2022 Apr.
Results Reference
derived
PubMed Identifier
34928484
Citation
Nadal E, Horinouchi H, Shih JY, Nakagawa K, Reck M, Garon EB, Wei YF, Kollmeier J, Frimodt-Moller B, Barrett E, Lipkovich O, Visseren-Grul C, Novello S. RELAY, Ramucirumab Plus Erlotinib Versus Placebo Plus Erlotinib in Patients with Untreated, Epidermal Growth Factor Receptor Mutation-Positive, Metastatic Non-Small-Cell Lung Cancer: Safety Profile and Manageability. Drug Saf. 2022 Jan;45(1):45-64. doi: 10.1007/s40264-021-01127-2. Epub 2021 Dec 20.
Results Reference
derived
PubMed Identifier
34795131
Citation
Mitani S, Chen Y, Inoue K, Mori J, Gao L, Long A, Wakabayashi S. Clinical Impact of a Shortened Infusion Duration of Ramucirumab in Japanese Patients -A Model-Based Approach. Gan To Kagaku Ryoho. 2021 Nov;48(11):1381-1387.
Results Reference
derived
PubMed Identifier
31591063
Citation
Nakagawa K, Garon EB, Seto T, Nishio M, Ponce Aix S, Paz-Ares L, Chiu CH, Park K, Novello S, Nadal E, Imamura F, Yoh K, Shih JY, Au KH, Moro-Sibilot D, Enatsu S, Zimmermann A, Frimodt-Moller B, Visseren-Grul C, Reck M; RELAY Study Investigators. Ramucirumab plus erlotinib in patients with untreated, EGFR-mutated, advanced non-small-cell lung cancer (RELAY): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019 Dec;20(12):1655-1669. doi: 10.1016/S1470-2045(19)30634-5. Epub 2019 Oct 4.
Results Reference
derived
PubMed Identifier
29317191
Citation
Reck M, Garon EB, Paz-Ares L, Ponce S, Jaime JC, Juan O, Nadal E, Kiura K, Widau RC, He S, Dalal R, Lee P, Nakagawa K. Randomized, Double-Blind Phase Ib/III Study of Erlotinib With Ramucirumab or Placebo in Previously Untreated EGFR-Mutant Metastatic Non-Small-Cell Lung Cancer (RELAY): Phase Ib Results. Clin Lung Cancer. 2018 May;19(3):213-220.e4. doi: 10.1016/j.cllc.2017.11.003. Epub 2017 Nov 21.
Results Reference
derived
PubMed Identifier
27894601
Citation
Garon EB, Reck M, Paz-Ares L, Ponce S, Jaime JC, Juan O, Nadal E, Lee P, Dalal R, Liu J, He S, Treat J, Nakagawa K. Treatment Rationale and Study Design for the RELAY Study: A Multicenter, Randomized, Double-Blind Study of Erlotinib With Ramucirumab or Placebo in Patients With Epidermal Growth Factor Receptor Mutation-Positive Metastatic Non-Small-Cell Lung Cancer. Clin Lung Cancer. 2017 Jan;18(1):96-99. doi: 10.1016/j.cllc.2016.05.023. Epub 2016 Jun 8.
Results Reference
derived
Links:
URL
https://trials.lillytrialguide.com/en-US/trial/3pxvd64nCo8AmAgMMu6iSo
Description
A Study of Ramucirumab (LY3009806) in Combination With Erlotinib in Participants With EGFR Mutation-Positive Metastatic NSCLC

Learn more about this trial

A Study of Ramucirumab (LY3009806) in Combination With Erlotinib in Previously Untreated Participants With EGFR Mutation-Positive Metastatic NSCLC (RELAY)

We'll reach out to this number within 24 hrs