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RAINFALL: A Study of Ramucirumab (LY3009806) in Combination With Capecitabine and Cisplatin in Participants With Stomach Cancer

Sponsor
Eli Lilly and Company (Industry)
Overall Status
Completed
CT.gov ID
NCT02314117
Collaborator
(none)
645
Enrollment
135
Locations
2
Arms
66.8
Actual Duration (Months)
4.8
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The main purpose of this study is to evaluate the efficacy of ramucirumab, which is a targeted antibody, in combination with capecitabine and cisplatin compared to capecitabine and cisplatin alone in participants with stomach cancer.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
645 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study of Capecitabine and Cisplatin With or Without Ramucirumab as First-line Therapy in Patients With Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma (RAINFALL)
Actual Study Start Date :
Jan 20, 2015
Actual Primary Completion Date :
Jan 17, 2017
Actual Study Completion Date :
Aug 14, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: Ramucirumab + Cisplatin + Capecitabine

8 milligrams/kilogram (mg/kg) ramucirumab given intravenously (IV) on days 1 and 8 in combination with 80 mg/square meter (m^2) cisplatin given IV on day 1 of each 21-day cycle (for up to 6 cycles) and 1000 mg/m^2 capecitabine given orally twice a day on days 1 through 14. Participants that were unable to take capecitabine will be given 800 mg/m^2/day fluorouracil (5-FU) IV on days 1 to 5 of each 21-day cycle.

Drug: Ramucirumab
Administered IV
Other Names:
  • LY3009806
  • IMC-1121B
  • Cyramza

    • Drug: Capecitabine
    Administered orally

    Drug: Cisplatin
    Administered IV

    Drug: Fluorouracil
    Administered IV
    Active Comparator: Placebo + Cisplatin + Capecitabine

    Placebo for blinding given IV on days 1 and 8 in combination with 80 mg/m^2 cisplatin given IV on day 1 of each 21-day cycle (for up to 6 cycles) and 1000 mg/m^2 capecitabine given orally twice a day on days 1 through 14. Participants that were unable to take capecitabine will be given 800 mg/m^2/day 5-FU IV on days 1 to 5 of each 21-day cycle.

    Drug: Capecitabine
    Administered orally

    Drug: Cisplatin
    Administered IV

    Drug: Placebo
    Administered IV

    Drug: Fluorouracil
    Administered IV

    Outcome Measures

    Primary Outcome Measures

    1. Progression-free Survival (PFS) [Randomization to Radiological Disease Progression or Death from Any Cause (Up to 26 Months)]

      PFS time was measured from the date of randomization to the date of radiographic(rgr) documentation of progression(by RECIST v.1.1) or the date of death due to any cause, whichever was earlier.If a participant did not have a complete baseline tumor assessment,then the PFS time was censored at the randomization date.If a participant was not known to have died or have rgr documented progression as of the data cutoff date for the analysis, the PFS time was censored at the last adequate tumor assessment date. If death or progressive disease(PD) occurred after 2 or more consecutive missing rgr visits,censoring occurred at the date of the last rgr visit prior to the missed visits.If death or PD occurred after postdiscontinuation(pdis) systemic anticancer therapy,censoring occurred at the date of last rgr visit prior to the start of pdis systemic anticancer therapy. PD was defined according to RECIST v.1.1.

    Secondary Outcome Measures

    1. Overall Survival (OS) [Randomization to Death from Any Cause (Up To 30 Months)]

      OS was time from the date of randomization to the date of death from any cause. If the participant was alive at the cutoff for analysis (or was lost to follow-up), OS data were censored for analysis on the last date the participant was known to be alive.

    2. Progression- Free Survival 2 (PFS2) [Randomization to Second Radiological or Symptomatic Disease Progression After the Start of Additional Systemic Anticancer Treatment or Death from Any Cause (Up To 26 Months)]

      PFS2 was defined as the time from the date of randomization to second disease progression (defined as objective radiological or symptomatic progression), or death of any cause, whichever occurs first. Participants alive and for whom a second disease progression has not been observed (including participants who did not receive any additional systemic anticancer treatments) were censored at the last time known to be alive and without second disease progression. The second progression refers to disease progression on or after additional systemic anticancer therapy, regardless if any earlier progression is observed or not(e.g. at the end of study treatment). It is assessed by investigator based on overall clinical evaluation, not limited to RECIST.

    3. Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR]) [Randomization to Disease Progression (Up To 26 Months)]

      Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST v1.1).Target lesions - CR: Disappearance of all lesions; any pathological lymph nodes must have reduction in short axis to <10 mm. PR: At least a 30% decrease in the sum of diameters of lesions vs the baseline sum. PD: At least a 20% increase in the sum of diameters of lesions vs the smallest sum on study (the sum must also demonstrate an absolute increase of at least 5 mm); or the appearance of new lesion(s). Non target lesions - CR: Disappearance of all lesions and normalization of tumor marker levels; all lymph nodes must be non-pathological in size. Non-CR/Non-PD: Persistence of lesion(s) and/or maintenance of abnormal tumor marker levels. PD: Unequivocal progression of existing lesions or the appearance of new lesion(s).ORR calculated as:(sum of the number of participants with PRs and CRs) divided by (number of evaluable participants) multiplied by 100.

    4. Percentage of Participants With Complete Response (CR), Partial Response (PR) or Stable Disease (SD) (Disease Control Rate [DCR]) [Randomization to Disease Progression (Up To 26 Months)]

      DCR was the percentage of participants with a best overall response of CR, PR, or SD as per Response using RECIST v1.1 criteria. Target lesions - CR: Disappearance of all lesions; any pathological lymph nodes must have reduction in short axis to <10 mm. PR: At least a 30% decrease in the sum of diameters of lesions vs the baseline sum. Progressive Disease (PD): At least a 20% increase in the sum of diameters of lesions vs the smallest sum on study (the sum must also demonstrate an absolute increase of at least 5 mm); or the appearance of new lesion(s). Stable Disease: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Non target lesions - CR: Disappearance of all lesions and normalization of tumor marker levels; all lymph nodes must be non-pathological in size. Non-CR/Non-PD: Persistence of lesion(s) and/or maintenance of abnormal tumor marker levels. PD: Unequivocal progression of existing lesions or the appearance of new lesion(s).

    5. Time to Progression (TTP) [Randomization to Disease Progression (Up To 24 Months)]

      TTP was time from the date of randomization to the date of radiographic progression (according to RECIST v.1.1). If a participant died due to any reason without radiographic progression, TTP is censored at the last adequate tumor assessment. Target lesions: Progressive Disease (PD): At least a 20% increase in the sum of diameters of lesions vs the smallest sum on study (the sum must also demonstrate an absolute increase of at least 5 mm); or the appearance of new lesion(s). Non target lesions: PD: Unequivocal progression of existing lesions or the appearance of new lesion(s).

    6. Duration of Response (DoR) [Date of Complete Response (CR) or Partial Response (PR) to Date of Objective Disease Progression or Death Due to Any Cause (Up To 26 Months)]

      Participants achieved an objective response if they had a best overall response of CR or PR.Target lesions- CR:Disappearance of all lesions;any pathological lymph nodes must have reduction in short axis to <10 mm.PR: At least a 30% decrease in the sum of diameters of lesions vs the baseline sum.PD: At least a 20% increase in the sum of diameters of lesions vs the smallest sum on study(the sum must also demonstrate an absolute increase of at least 5 mm); or the appearance of new lesion(s).Non target lesions - CR: Disappearance of all lesions and normalization of tumour marker levels;all lymph nodes must be non-pathological in size. Non-CR/Non-PD:Persistence of lesion(s) and/or maintenance of abnormal tumor marker levels.PD:Unequivocal progression of existing lesions or the appearance of new lesion(s).If a participant was not known to have died or have radiographically documented PD as of the data inclusion cutoff date,DOR was censored at the date of the last adequate tumor assessment.

    7. Time to Deterioration in Quality of Life (QoL) on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) - Global Health Status/ QoL Scale [Randomization, First worsening in QoL (Up To 26 Months)]

      Time to sustained deterioration was defined as time from randomization to first worsening in QoL with no subsequent non-worsened assessment. Worsening in global health status/QoL was defined as a decrease of ≥10 points on a 100-point scale. If a participant did not report worsening, time to sustained deterioration was censored at date of last non-worsened assessment.

    8. Change in Health Status on the EuroQol 5-Dimensions 5-Level Instrument (EQ-5D- 5L) [Randomization, 30 Days After Treatment Discontinuation (Up To 5 Months)]

      The EQ-5D-5L is a standardized instrument for use as a measure of self-reported health status. Five dimensions of health status are each assessed with 5 response options and scored as a composite index which were anchored on a scale of 0 to 1 with a higher score representing better health status. Additionally, current health status was assessed on a visual analogue scale (VAS) ranging from 0 to 100 with a higher score representing better health status.

    9. Time to Deterioration in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) [Randomization to ECOG PS ≥2 (Up To 26 Months)]

      The time from the date of randomization to the first date observing ECOG PS ≥2 (that is, deterioration from baseline status of 0 or 1). Participants without PS deterioration were censored at their last documented assessments of 0 or 1. ECOG Performance Status: 2- Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours, 3 -Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours, 4 -Completely disabled. Cannot carry on any selfcare.Totally confined to bed or chair,5- Dead.

    10. Number of Participants With Anti-Ramucirumab Antibodies [Predose Cycle 1 through 30 Days After Treatment Discontinuation (Up To 24 Months)]

      Participants who developed treatment-emergent antibody responses to Ramucirumab postbaseline.

    11. Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Ramucirumab [Cycle 1 Day 1: 1 hour (hr) end of infusion (EOI), Cycle 3 Day 1: 1hr EOI, Cycle 9 Day 1: 1 hr EOI]

      Pharmacokinetics (PK): Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Ramucirumab

    12. PK: Minimum Concentration (Cmin) of Ramucirumab [Cycle 1 Day 1: 1 hour (hr) end of infusion (EOI), Cycle 3 Day 1: 1hr EOI, Cycle 9 Day 1: 1 hr EOI]

      Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Have a histopathologically confirmed diagnosis of metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma. All histologies of nonsquamous cell origin including undifferentiated gastric carcinoma are eligible.

    • Have not received any prior first-line systemic therapy (prior adjuvant or neo-adjuvant therapy is permitted). Participants whose disease has progressed after

    12 months following the last dose of systemic treatment in the adjuvant/neoadjuvant setting are eligible.

    • Have measurable or nonmeasurable but evaluable disease determined using guidelines in Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v 1.1). Baseline tumor assessment should be performed using a high resolution computed tomography (CT) scan using IV and oral contrast unless clinically contra-indicated. Magnetic resonance imaging (MRI) is acceptable if a CT cannot be performed.

    • Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group scale at baseline.

    • Have adequate organ function.

    • Have baseline clinical and laboratory parameters that are consistent with the requirements prescribed in respective labels and are suitable for consideration of treatment with capecitabine (or 5-FU) and cisplatin (for example, dihydropyrimidine dehydrogenase deficiency).

    • Have an estimated life expectancy of ≥12 weeks in the judgment of the investigator.

    Exclusion Criteria:

    • Participants with adenocarcinoma of the esophagus are excluded.

    • Participants with human epidermal growth factor receptor 2 (HER2)-positive status.

    • Participants receiving chronic therapy with nonsteroidal anti-inflammatory agents.

    • Have radiation therapy within 14 days prior to randomization.

    • Have documented brain metastases, leptomeningeal disease or uncontrolled spinal cord compression.

    • Have significant bleeding disorders, vasculitis, or had a significant bleeding episode from the gastrointestinal tract within 12 weeks prior to randomization.

    • Have experienced any arterial thromboembolic event, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack, within 6 months prior to randomization.

    • Have symptomatic congestive heart failure (New York Heart Association II-IV) or symptomatic or poorly controlled cardiac arrhythmia.

    • Have uncontrolled hypertension prior to initiating study treatment, despite antihypertensive intervention.

    • Have undergone major surgery within 28 days prior to randomization, or central venous access device placement within 7 days prior to first dose of study treatment, except if the procedure is minimally invasive (for example, introduction of peripherally inserted central catheter [PICC] line) and the investigator does not anticipate any significant bleeding.

    • Have a history of gastrointestinal perforation and/or fistulae within 6 months prior to randomization.

    • Have a history of inflammatory bowel disease or Crohn's disease requiring medical intervention (immunomodulatory or immunosuppressive medications or surgery) ≤12 months prior to randomization.

    • Have an acute or subacute bowel obstruction or history of chronic diarrhea which is considered clinically significant in the opinion of the investigator.

    • The participant has:

    • cirrhosis at a level of Child-Pugh B (or worse) or

    • cirrhosis (any degree) and a history of hepatic encephalopathy or clinically meaningful ascites resulting from cirrhosis. Clinically meaningful ascites is defined as ascites resulting from cirrhosis and requiring ongoing treatment with diuretics and/or paracentesis.

    • Have known allergy or hypersensitivity to any components of study treatment.

    • Are pregnant or lactating.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Highlands Oncology Group Fayetteville Arkansas United States 72703
    2 Comprehensive Blood and Cancer Center Bakersfield California United States 93309
    3 St Jude Medical Center Fullerton California United States 92835
    4 SMO TRIO -Translational Research Los Angeles California United States 90024
    5 UCLA Medical Center Los Angeles California United States 90024
    6 Cancer Care Associates Medical Group Redondo Beach California United States 90277
    7 Coastal Integrative Cancer Care San Luis Obispo California United States 93401
    8 Central Coast Medical Oncology Corporation Santa Monica California United States 93454
    9 University of Colorado School of Medicine Aurora Colorado United States 80045
    10 Yale University School of Medicine New Haven Connecticut United States 06520-8020
    11 Holy Cross Hospital Inc. Fort Lauderdale Florida United States 33308
    12 Florida Cancer Specialists Fort Myers Florida United States 33916
    13 Florida Cancer Specialists and Research Institute Saint Petersburg Florida United States 33705
    14 Emory University Atlanta Georgia United States 30322
    15 Illinois CancerCare Peoria Illinois United States 61615
    16 Dana Farber Cancer Institute Boston Massachusetts United States 02215
    17 Weill Cornell Medical College New York New York United States 10021
    18 Memorial Sloan Kettering Cancer Center New York New York United States 10065
    19 Oncology Hematology Care Inc Cincinnati Ohio United States 45242
    20 Fox Chase Cancer Center Philadelphia Pennsylvania United States 19111-2497
    21 Allegheny General Hospital Pittsburgh Pennsylvania United States 15212
    22 SMO Sarah Cannon Research Inst. Nashville Tennessee United States 37203
    23 Tennessee Oncology PLLC Nashville Tennessee United States 37203
    24 UT Southwestern Med Ctr Dallas Texas United States 75390
    25 Baylor College of Medicine Houston Texas United States 77030
    26 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. Viedma Rio Negro Argentina 8500
    27 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. Rosario Santa Fe Argentina 2000
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    29 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. La Rioja Argentina 5300
    30 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. Rosario Argentina S2002KDS
    31 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. Salta Argentina 4400
    32 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. Brussels Belgium 1200
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    34 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. Gent Belgium 9000
    35 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. Leuven Belgium 3000
    36 For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician. Montreal Canada H2L 4M1
    37 For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician. Montreal Canada H4A 3J1
    38 For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician. Ottawa Canada K1H 8L6
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    43 For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician. Vancouver Canada V5Z 4E6
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    54 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. Turku Finland SF-20520
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    56 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. Clermont-Ferrand France 63003
    57 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. Lille France 59037
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    64 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. Hamburg Germany 20249
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    71 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. Szolnok Hungary 5000
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    114 Ad-Vance Medical Research Ponce Puerto Rico 00717
    115 Hospital Espanol Auxilio Mutuo San Juan Puerto Rico 00918
    116 VA Caribbean Healthcare System San Juan Puerto Rico 00921-3201
    117 Hospital Municipal de San Juan San Juan Puerto Rico 00935
    118 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. Arkhangelsk Russian Federation 163045
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    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

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Eli Lilly and Company
    ClinicalTrials.gov Identifier:
    NCT02314117
    Other Study ID Numbers:
    • 15372
    • I4T-MC-JVCU
    • 2014-002240-40
    First Posted:
    Dec 10, 2014
    Last Update Posted:
    Aug 26, 2021
    Last Verified:
    Jul 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Adenocarcinoma
    Esophageal Neoplasms
    Fluorouracil
    Capecitabine
    Ramucirumab

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail Completers are defined as participants who died or those who were alive and off treatment when the study completed.
    Arm/Group Title Ramucirumab + Cisplatin + Capecitabine Placebo + Cisplatin + Capecitabine
    Arm/Group Description 8 milligrams/kilogram (mg/kg) ramucirumab given intravenously (IV) on days 1 and 8 in combination with 80 mg/square meter (m^2) cisplatin given IV on day 1 of each 21-day cycle (for up to 6 cycles) and 1000 mg/m^2 capecitabine given orally twice a day on days 1 through 14. Participants that were unable to take capecitabine will be given 800 mg/m^2/day fluorouracil (5-FU) IV on days 1 to 5 of each 21-day cycle. Placebo for blinding given IV on days 1 and 8 in combination with 80 mg/m^2 cisplatin given IV on day 1 of each 21-day cycle (for up to 6 cycles) and 1000 mg/m^2 capecitabine given orally twice a day on days 1 through 14. Participants that were unable to take capecitabine will be given 800 mg/m^2/day 5-FU IV on days 1 to 5 of each 21-day cycle.
    Period Title: Overall Study
    STARTED 326 319
    Received at Least One Dose of Study Drug 323 315
    COMPLETED 314 303
    NOT COMPLETED 12 16

    Baseline Characteristics

    Arm/Group Title Ramucirumab + Cisplatin + Capecitabine Placebo + Cisplatin + Capecitabine Total
    Arm/Group Description 8 milligrams/kilogram (mg/kg) ramucirumab given intravenously (IV) on days 1 and 8 in combination with 80 mg/square meter (m^2) cisplatin given IV on day 1 of each 21-day cycle (for up to 6 cycles) and 1000 mg/m^2 capecitabine given orally twice a day on days 1 through 14. Participants that were unable to take capecitabine will be given 800 mg/m^2/day fluorouracil (5-FU) IV on days 1 to 5 of each 21-day cycle. Placebo for blinding given IV on days 1 and 8 in combination with 80 mg/m^2 cisplatin given IV on day 1 of each 21-day cycle (for up to 6 cycles) and 1000 mg/m^2 capecitabine given orally twice a day on days 1 through 14. Participants that were unable to take capecitabine will be given 800 mg/m^2/day 5-FU IV on days 1 to 5 of each 21-day cycle. Total of all reporting groups
    Overall Participants 326 319 645
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    58.9
    (11.6)
    60.1
    (11.8)
    59.5
    (11.7)
    Sex: Female, Male (Count of Participants)
    Female
    112
    34.4%
    104
    32.6%
    216
    33.5%
    Male
    214
    65.6%
    215
    67.4%
    429
    66.5%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    67
    20.6%
    62
    19.4%
    129
    20%
    Not Hispanic or Latino
    227
    69.6%
    245
    76.8%
    472
    73.2%
    Unknown or Not Reported
    32
    9.8%
    12
    3.8%
    44
    6.8%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    12
    3.7%
    11
    3.4%
    23
    3.6%
    Asian
    38
    11.7%
    31
    9.7%
    69
    10.7%
    Native Hawaiian or Other Pacific Islander
    1
    0.3%
    0
    0%
    1
    0.2%
    Black or African American
    2
    0.6%
    3
    0.9%
    5
    0.8%
    White
    256
    78.5%
    264
    82.8%
    520
    80.6%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    17
    5.2%
    10
    3.1%
    27
    4.2%
    Region of Enrollment (Count of Participants)
    Puerto Rico
    1
    0.3%
    1
    0.3%
    2
    0.3%
    Argentina
    21
    6.4%
    22
    6.9%
    43
    6.7%
    Hungary
    15
    4.6%
    16
    5%
    31
    4.8%
    United States
    42
    12.9%
    31
    9.7%
    73
    11.3%
    Czechia
    11
    3.4%
    8
    2.5%
    19
    2.9%
    Japan
    32
    9.8%
    28
    8.8%
    60
    9.3%
    United Kingdom
    20
    6.1%
    22
    6.9%
    42
    6.5%
    Russia
    25
    7.7%
    25
    7.8%
    50
    7.8%
    Spain
    10
    3.1%
    13
    4.1%
    23
    3.6%
    Canada
    10
    3.1%
    6
    1.9%
    16
    2.5%
    Netherlands
    4
    1.2%
    7
    2.2%
    11
    1.7%
    Belgium
    8
    2.5%
    5
    1.6%
    13
    2%
    Finland
    3
    0.9%
    5
    1.6%
    8
    1.2%
    Denmark
    12
    3.7%
    3
    0.9%
    15
    2.3%
    Poland
    8
    2.5%
    10
    3.1%
    18
    2.8%
    Italy
    28
    8.6%
    45
    14.1%
    73
    11.3%
    Mexico
    26
    8%
    26
    8.2%
    52
    8.1%
    Israel
    11
    3.4%
    12
    3.8%
    23
    3.6%
    France
    19
    5.8%
    21
    6.6%
    40
    6.2%
    Germany
    20
    6.1%
    13
    4.1%
    33
    5.1%

    Outcome Measures

    1. Primary Outcome
    Title Progression-free Survival (PFS)
    Description PFS time was measured from the date of randomization to the date of radiographic(rgr) documentation of progression(by RECIST v.1.1) or the date of death due to any cause, whichever was earlier.If a participant did not have a complete baseline tumor assessment,then the PFS time was censored at the randomization date.If a participant was not known to have died or have rgr documented progression as of the data cutoff date for the analysis, the PFS time was censored at the last adequate tumor assessment date. If death or progressive disease(PD) occurred after 2 or more consecutive missing rgr visits,censoring occurred at the date of the last rgr visit prior to the missed visits.If death or PD occurred after postdiscontinuation(pdis) systemic anticancer therapy,censoring occurred at the date of last rgr visit prior to the start of pdis systemic anticancer therapy. PD was defined according to RECIST v.1.1.
    Time Frame Randomization to Radiological Disease Progression or Death from Any Cause (Up to 26 Months)

    Outcome Measure Data

    Analysis Population Description
    First 508 randomized participants. Participants censored: Ramucirumab + Cisplatin + Capecitabine=87 and Placebo + Cisplatin + Capecitabine=62.
    Arm/Group Title Ramucirumab + Cisplatin + Capecitabine Placebo + Cisplatin + Capecitabine
    Arm/Group Description 8 milligrams/kilogram (mg/kg) ramucirumab given intravenously (IV) on days 1 and 8 in combination with 80 mg/square meter (m^2) cisplatin given IV on day 1 of each 21-day cycle (for up to 6 cycles) and 1000 mg/m^2 capecitabine given orally twice a day on days 1 through 14. Participants that were unable to take capecitabine will be given 800 mg/m^2/day fluorouracil (5-FU) IV on days 1 to 5 of each 21-day cycle. Placebo for blinding given IV on days 1 and 8 in combination with 80 mg/m^2 cisplatin given IV on day 1 of each 21-day cycle (for up to 6 cycles) and 1000 mg/m^2 capecitabine given orally twice a day on days 1 through 14. Participants that were unable to take capecitabine will be given 800 mg/m^2/day 5-FU IV on days 1 to 5 of each 21-day cycle.
    Measure Participants 255 253
    Median (95% Confidence Interval) [months]
    5.72
    5.39
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ramucirumab + Cisplatin + Capecitabine, Placebo + Cisplatin + Capecitabine
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.753
    Confidence Interval (2-Sided) 95%
    0.607 to 0.935
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Overall Survival (OS)
    Description OS was time from the date of randomization to the date of death from any cause. If the participant was alive at the cutoff for analysis (or was lost to follow-up), OS data were censored for analysis on the last date the participant was known to be alive.
    Time Frame Randomization to Death from Any Cause (Up To 30 Months)

    Outcome Measure Data

    Analysis Population Description
    All randomized participants. Participants censored: Ramucirumab + Cisplatin + Capecitabine=87 and Placebo + Cisplatin + Capecitabine=88.
    Arm/Group Title Ramucirumab + Cisplatin + Capecitabine Placebo + Cisplatin + Capecitabine
    Arm/Group Description 8 milligrams/kilogram (mg/kg) ramucirumab given intravenously (IV) on days 1 and 8 in combination with 80 mg/square meter (m^2) cisplatin given IV on day 1 of each 21-day cycle (for up to 6 cycles) and 1000 mg/m^2 capecitabine given orally twice a day on days 1 through 14. Participants that were unable to take capecitabine will be given 800 mg/m^2/day fluorouracil (5-FU) IV on days 1 to 5 of each 21-day cycle. Placebo for blinding given IV on days 1 and 8 in combination with 80 mg/m^2 cisplatin given IV on day 1 of each 21-day cycle (for up to 6 cycles) and 1000 mg/m^2 capecitabine given orally twice a day on days 1 through 14. Participants that were unable to take capecitabine will be given 800 mg/m^2/day 5-FU IV on days 1 to 5 of each 21-day cycle.
    Measure Participants 326 319
    Median (95% Confidence Interval) [months]
    11.17
    10.74
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ramucirumab + Cisplatin + Capecitabine, Placebo + Cisplatin + Capecitabine
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.962
    Confidence Interval (2-Sided) 95%
    0.801 to 1.156
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Secondary Outcome
    Title Progression- Free Survival 2 (PFS2)
    Description PFS2 was defined as the time from the date of randomization to second disease progression (defined as objective radiological or symptomatic progression), or death of any cause, whichever occurs first. Participants alive and for whom a second disease progression has not been observed (including participants who did not receive any additional systemic anticancer treatments) were censored at the last time known to be alive and without second disease progression. The second progression refers to disease progression on or after additional systemic anticancer therapy, regardless if any earlier progression is observed or not(e.g. at the end of study treatment). It is assessed by investigator based on overall clinical evaluation, not limited to RECIST.
    Time Frame Randomization to Second Radiological or Symptomatic Disease Progression After the Start of Additional Systemic Anticancer Treatment or Death from Any Cause (Up To 26 Months)

    Outcome Measure Data

    Analysis Population Description
    All randomized participants. Participants censored: Ramucirumab + Cisplatin + Capecitabine=74 and Placebo + Cisplatin + Capecitabine=74.
    Arm/Group Title Ramucirumab + Cisplatin + Capecitabine Placebo + Cisplatin + Capecitabine
    Arm/Group Description 8 milligrams/kilogram (mg/kg) ramucirumab given intravenously (IV) on days 1 and 8 in combination with 80 mg/square meter (m^2) cisplatin given IV on day 1 of each 21-day cycle (for up to 6 cycles) and 1000 mg/m^2 capecitabine given orally twice a day on days 1 through 14. Participants that were unable to take capecitabine will be given 800 mg/m^2/day fluorouracil (5-FU) IV on days 1 to 5 of each 21-day cycle. Placebo for blinding given IV on days 1 and 8 in combination with 80 mg/m^2 cisplatin given IV on day 1 of each 21-day cycle (for up to 6 cycles) and 1000 mg/m^2 capecitabine given orally twice a day on days 1 through 14. Participants that were unable to take capecitabine will be given 800 mg/m^2/day 5-FU IV on days 1 to 5 of each 21-day cycle.
    Measure Participants 326 319
    Median (95% Confidence Interval) [months]
    10.18
    9.20
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ramucirumab + Cisplatin + Capecitabine, Placebo + Cisplatin + Capecitabine
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.926
    Confidence Interval (2-Sided) 95%
    0.774 to 1.108
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    4. Secondary Outcome
    Title Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])
    Description Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST v1.1).Target lesions - CR: Disappearance of all lesions; any pathological lymph nodes must have reduction in short axis to <10 mm. PR: At least a 30% decrease in the sum of diameters of lesions vs the baseline sum. PD: At least a 20% increase in the sum of diameters of lesions vs the smallest sum on study (the sum must also demonstrate an absolute increase of at least 5 mm); or the appearance of new lesion(s). Non target lesions - CR: Disappearance of all lesions and normalization of tumor marker levels; all lymph nodes must be non-pathological in size. Non-CR/Non-PD: Persistence of lesion(s) and/or maintenance of abnormal tumor marker levels. PD: Unequivocal progression of existing lesions or the appearance of new lesion(s).ORR calculated as:(sum of the number of participants with PRs and CRs) divided by (number of evaluable participants) multiplied by 100.
    Time Frame Randomization to Disease Progression (Up To 26 Months)

    Outcome Measure Data

    Analysis Population Description
    All randomized participants.
    Arm/Group Title Ramucirumab + Cisplatin + Capecitabine Placebo + Cisplatin + Capecitabine
    Arm/Group Description 8 milligrams/kilogram (mg/kg) ramucirumab given intravenously (IV) on days 1 and 8 in combination with 80 mg/square meter (m^2) cisplatin given IV on day 1 of each 21-day cycle (for up to 6 cycles) and 1000 mg/m^2 capecitabine given orally twice a day on days 1 through 14. Participants that were unable to take capecitabine will be given 800 mg/m^2/day fluorouracil (5-FU) IV on days 1 to 5 of each 21-day cycle. Placebo for blinding given IV on days 1 and 8 in combination with 80 mg/m^2 cisplatin given IV on day 1 of each 21-day cycle (for up to 6 cycles) and 1000 mg/m^2 capecitabine given orally twice a day on days 1 through 14. Participants that were unable to take capecitabine will be given 800 mg/m^2/day 5-FU IV on days 1 to 5 of each 21-day cycle.
    Measure Participants 326 319
    Number (95% Confidence Interval) [percentage of participants]
    41.1
    12.6%
    36.4
    11.4%
    5. Secondary Outcome
    Title Percentage of Participants With Complete Response (CR), Partial Response (PR) or Stable Disease (SD) (Disease Control Rate [DCR])
    Description DCR was the percentage of participants with a best overall response of CR, PR, or SD as per Response using RECIST v1.1 criteria. Target lesions - CR: Disappearance of all lesions; any pathological lymph nodes must have reduction in short axis to <10 mm. PR: At least a 30% decrease in the sum of diameters of lesions vs the baseline sum. Progressive Disease (PD): At least a 20% increase in the sum of diameters of lesions vs the smallest sum on study (the sum must also demonstrate an absolute increase of at least 5 mm); or the appearance of new lesion(s). Stable Disease: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Non target lesions - CR: Disappearance of all lesions and normalization of tumor marker levels; all lymph nodes must be non-pathological in size. Non-CR/Non-PD: Persistence of lesion(s) and/or maintenance of abnormal tumor marker levels. PD: Unequivocal progression of existing lesions or the appearance of new lesion(s).
    Time Frame Randomization to Disease Progression (Up To 26 Months)

    Outcome Measure Data

    Analysis Population Description
    All randomized participants.
    Arm/Group Title Ramucirumab + Cisplatin + Capecitabine Placebo + Cisplatin + Capecitabine
    Arm/Group Description 8 milligrams/kilogram (mg/kg) ramucirumab given intravenously (IV) on days 1 and 8 in combination with 80 mg/square meter (m^2) cisplatin given IV on day 1 of each 21-day cycle (for up to 6 cycles) and 1000 mg/m^2 capecitabine given orally twice a day on days 1 through 14. Participants that were unable to take capecitabine will be given 800 mg/m^2/day fluorouracil (5-FU) IV on days 1 to 5 of each 21-day cycle. Placebo for blinding given IV on days 1 and 8 in combination with 80 mg/m^2 cisplatin given IV on day 1 of each 21 day cycle (for up to 6 cycles) and 1000 mg/m^2 capecitabine given orally twice a day on days 1 through 14. Participants that are unable to take capecitabine will be given 800 mg/m^2/day 5-FU IV on days 1 to 5 of each 21 day cycle.
    Measure Participants 326 319
    Number (95% Confidence Interval) [percentage of participants]
    81.9
    25.1%
    76.5
    24%
    6. Secondary Outcome
    Title Time to Progression (TTP)
    Description TTP was time from the date of randomization to the date of radiographic progression (according to RECIST v.1.1). If a participant died due to any reason without radiographic progression, TTP is censored at the last adequate tumor assessment. Target lesions: Progressive Disease (PD): At least a 20% increase in the sum of diameters of lesions vs the smallest sum on study (the sum must also demonstrate an absolute increase of at least 5 mm); or the appearance of new lesion(s). Non target lesions: PD: Unequivocal progression of existing lesions or the appearance of new lesion(s).
    Time Frame Randomization to Disease Progression (Up To 24 Months)

    Outcome Measure Data

    Analysis Population Description
    All randomized participants. Participants censored: Ramucirumab + Cisplatin + Capecitabine=149 and Placebo + Cisplatin + Capecitabine=111.
    Arm/Group Title Ramucirumab + Cisplatin + Capecitabine Placebo + Cisplatin + Capecitabine
    Arm/Group Description 8 milligrams/kilogram (mg/kg) ramucirumab given intravenously (IV) on days 1 and 8 in combination with 80 mg/square meter (m^2) cisplatin given IV on day 1 of each 21-day cycle (for up to 6 cycles) and 1000 mg/m^2 capecitabine given orally twice a day on days 1 through 14. Participants that were unable to take capecitabine will be given 800 mg/m^2/day fluorouracil (5-FU) IV on days 1 to 5 of each 21-day cycle. Placebo for blinding given IV on days 1 and 8 in combination with 80 mg/m^2 cisplatin given IV on day 1 of each 21 day cycle (for up to 6 cycles) and 1000 mg/m^2 capecitabine given orally twice a day on days 1 through 14. Participants that are unable to take capecitabine will be given 800 mg/m^2/day 5-FU IV on days 1 to 5 of each 21 day cycle.
    Measure Participants 326 319
    Median (95% Confidence Interval) [months]
    6.77
    5.78
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ramucirumab + Cisplatin + Capecitabine, Placebo + Cisplatin + Capecitabine
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.699
    Confidence Interval (2-Sided) 95%
    0.569 to 0.859
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    7. Secondary Outcome
    Title Duration of Response (DoR)
    Description Participants achieved an objective response if they had a best overall response of CR or PR.Target lesions- CR:Disappearance of all lesions;any pathological lymph nodes must have reduction in short axis to <10 mm.PR: At least a 30% decrease in the sum of diameters of lesions vs the baseline sum.PD: At least a 20% increase in the sum of diameters of lesions vs the smallest sum on study(the sum must also demonstrate an absolute increase of at least 5 mm); or the appearance of new lesion(s).Non target lesions - CR: Disappearance of all lesions and normalization of tumour marker levels;all lymph nodes must be non-pathological in size. Non-CR/Non-PD:Persistence of lesion(s) and/or maintenance of abnormal tumor marker levels.PD:Unequivocal progression of existing lesions or the appearance of new lesion(s).If a participant was not known to have died or have radiographically documented PD as of the data inclusion cutoff date,DOR was censored at the date of the last adequate tumor assessment.
    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 26 Months)

    Outcome Measure Data

    Analysis Population Description
    All randomized participants. Participants censored : Ramucirumab + Cisplatin + Capecitabine= 23 and Placebo + Cisplatin + Capecitabine=10.
    Arm/Group Title Ramucirumab + Cisplatin + Capecitabine Placebo + Cisplatin + Capecitabine
    Arm/Group Description 8 milligrams/kilogram (mg/kg) ramucirumab given intravenously (IV) on days 1 and 8 in combination with 80 mg/square meter (m^2) cisplatin given IV on day 1 of each 21-day cycle (for up to 6 cycles) and 1000 mg/m^2 capecitabine given orally twice a day on days 1 through 14. Participants that were unable to take capecitabine will be given 800 mg/m^2/day fluorouracil (5-FU) IV on days 1 to 5 of each 21-day cycle. Placebo for blinding given IV on days 1 and 8 in combination with 80 mg/m^2 cisplatin given IV on day 1 of each 21-day cycle (for up to 6 cycles) and 1000 mg/m^2 capecitabine given orally twice a day on days 1 through 14. Participants that were unable to take capecitabine will be given 800 mg/m^2/day 5-FU IV on days 1 to 5 of each 21-day cycle.
    Measure Participants 134 116
    Median (95% Confidence Interval) [months]
    5.72
    4.27
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ramucirumab + Cisplatin + Capecitabine, Placebo + Cisplatin + Capecitabine
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.657
    Confidence Interval (2-Sided) 95%
    0.499 to 0.866
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    8. Secondary Outcome
    Title Time to Deterioration in Quality of Life (QoL) on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) - Global Health Status/ QoL Scale
    Description Time to sustained deterioration was defined as time from randomization to first worsening in QoL with no subsequent non-worsened assessment. Worsening in global health status/QoL was defined as a decrease of ≥10 points on a 100-point scale. If a participant did not report worsening, time to sustained deterioration was censored at date of last non-worsened assessment.
    Time Frame Randomization, First worsening in QoL (Up To 26 Months)

    Outcome Measure Data

    Analysis Population Description
    All randomized participants. Participants censored: Ramucirumab + Cisplatin + Capecitabine=215 and Placebo + Cisplatin + Capecitabine=217
    Arm/Group Title Ramucirumab + Cisplatin + Capecitabine Placebo + Cisplatin + Capecitabine
    Arm/Group Description 8 milligrams/kilogram (mg/kg) ramucirumab given intravenously (IV) on days 1 and 8 in combination with 80 mg/square meter (m^2) cisplatin given IV on day 1 of each 21-day cycle (for up to 6 cycles) and 1000 mg/m^2 capecitabine given orally twice a day on days 1 through 14. Participants that were unable to take capecitabine will be given 800 mg/m^2/day fluorouracil (5-FU) IV on days 1 to 5 of each 21-day cycle. Placebo for blinding given IV on days 1 and 8 in combination with 80 mg/m^2 cisplatin given IV on day 1 of each 21-day cycle (for up to 6 cycles) and 1000 mg/m^2 capecitabine given orally twice a day on days 1 through 14. Participants that were unable to take capecitabine will be given 800 mg/m^2/day 5-FU IV on days 1 to 5 of each 21-day cycle.
    Measure Participants 326 319
    Median (95% Confidence Interval) [months]
    9.00
    9.46
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ramucirumab + Cisplatin + Capecitabine, Placebo + Cisplatin + Capecitabine
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.013
    Confidence Interval (2-Sided) 95%
    0.770 to 1.332
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    9. Secondary Outcome
    Title Change in Health Status on the EuroQol 5-Dimensions 5-Level Instrument (EQ-5D- 5L)
    Description The EQ-5D-5L is a standardized instrument for use as a measure of self-reported health status. Five dimensions of health status are each assessed with 5 response options and scored as a composite index which were anchored on a scale of 0 to 1 with a higher score representing better health status. Additionally, current health status was assessed on a visual analogue scale (VAS) ranging from 0 to 100 with a higher score representing better health status.
    Time Frame Randomization, 30 Days After Treatment Discontinuation (Up To 5 Months)

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who provided data at baseline and cycle 6.
    Arm/Group Title Ramucirumab + Cisplatin + Capecitabine Placebo + Cisplatin + Capecitabine
    Arm/Group Description 8 milligrams/kilogram (mg/kg) ramucirumab given intravenously (IV) on days 1 and 8 in combination with 80 mg/square meter (m^2) cisplatin given IV on day 1 of each 21-day cycle (for up to 6 cycles) and 1000 mg/m^2 capecitabine given orally twice a day on days 1 through 14. Participants that were unable to take capecitabine will be given 800 mg/m^2/day fluorouracil (5-FU) IV on days 1 to 5 of each 21-day cycle. Placebo for blinding given IV on days 1 and 8 in combination with 80 mg/m^2 cisplatin given IV on day 1 of each 21-day cycle (for up to 6 cycles) and 1000 mg/m^2 capecitabine given orally twice a day on days 1 through 14. Participants that were unable to take capecitabine will be given 800 mg/m^2/day 5-FU IV on days 1 to 5 of each 21-day cycle.
    Measure Participants 136 125
    EQ-5D index
    -0.008
    (0.148)
    -0.010
    (0.157)
    EQ-5D VAS
    0.8
    (18.56)
    1.5
    (20.33)
    10. Secondary Outcome
    Title Time to Deterioration in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)
    Description The time from the date of randomization to the first date observing ECOG PS ≥2 (that is, deterioration from baseline status of 0 or 1). Participants without PS deterioration were censored at their last documented assessments of 0 or 1. ECOG Performance Status: 2- Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours, 3 -Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours, 4 -Completely disabled. Cannot carry on any selfcare.Totally confined to bed or chair,5- Dead.
    Time Frame Randomization to ECOG PS ≥2 (Up To 26 Months)

    Outcome Measure Data

    Analysis Population Description
    All randomized participants. Participants censored: Ramucirumab + Cisplatin + Capecitabine=254 and Placebo + Cisplatin + Capecitabine= 260.
    Arm/Group Title Ramucirumab + Cisplatin + Capecitabine Placebo + Cisplatin + Capecitabine
    Arm/Group Description 8 milligrams/kilogram (mg/kg) ramucirumab given intravenously (IV) on days 1 and 8 in combination with 80 mg/square meter (m^2) cisplatin given IV on day 1 of each 21-day cycle (for up to 6 cycles) and 1000 mg/m^2 capecitabine given orally twice a day on days 1 through 14. Participants that were unable to take capecitabine will be given 800 mg/m^2/day fluorouracil (5-FU) IV on days 1 to 5 of each 21-day cycle. Placebo for blinding given IV on days 1 and 8 in combination with 80 mg/m^2 cisplatin given IV on day 1 of each 21-day cycle (for up to 6 cycles) and 1000 mg/m^2 capecitabine given orally twice a day on days 1 through 14. Participants that were unable to take capecitabine will be given 800 mg/m^2/day 5-FU IV on days 1 to 5 of each 21-day cycle.
    Measure Participants 326 319
    Median (95% Confidence Interval) [months]
    NA
    NA
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ramucirumab + Cisplatin + Capecitabine, Placebo + Cisplatin + Capecitabine
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.117
    Confidence Interval (2-Sided) 95%
    0.790 to 1.580
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    11. Secondary Outcome
    Title Number of Participants With Anti-Ramucirumab Antibodies
    Description Participants who developed treatment-emergent antibody responses to Ramucirumab postbaseline.
    Time Frame Predose Cycle 1 through 30 Days After Treatment Discontinuation (Up To 24 Months)

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study drug.
    Arm/Group Title Ramucirumab + Cisplatin + Capecitabine Placebo + Cisplatin + Capecitabine
    Arm/Group Description 8 milligrams/kilogram (mg/kg) ramucirumab given intravenously (IV) on days 1 and 8 in combination with 80 mg/square meter (m^2) cisplatin given IV on day 1 of each 21-day cycle (for up to 6 cycles) and 1000 mg/m^2 capecitabine given orally twice a day on days 1 through 14. Participants that were unable to take capecitabine will be given 800 mg/m^2/day fluorouracil (5-FU) IV on days 1 to 5 of each 21-day cycle. Placebo for blinding given IV on days 1 and 8 in combination with 80 mg/m^2 cisplatin given IV on day 1 of each 21-day cycle (for up to 6 cycles) and 1000 mg/m^2 capecitabine given orally twice a day on days 1 through 14. Participants that were unable to take capecitabine will be given 800 mg/m^2/day 5-FU IV on days 1 to 5 of each 21-day cycle.
    Measure Participants 323 315
    Count of Participants [Participants]
    4
    1.2%
    5
    1.6%
    12. Secondary Outcome
    Title Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Ramucirumab
    Description Pharmacokinetics (PK): Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Ramucirumab
    Time Frame Cycle 1 Day 1: 1 hour (hr) end of infusion (EOI), Cycle 3 Day 1: 1hr EOI, Cycle 9 Day 1: 1 hr EOI

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received ramucirumab and had evaluable PK data.
    Arm/Group Title Ramucirumab + Cisplatin + Capecitabine
    Arm/Group Description 8 milligrams/kilogram (mg/kg) ramucirumab given intravenously (IV) on days 1 and 8 in combination with 80 mg/square meter (m^2) cisplatin given IV on day 1 of each 21-day cycle (for up to 6 cycles) and 1000 mg/m^2 capecitabine given orally twice a day on days 1 through 14. Participants that were unable to take capecitabine will be given 800 mg/m^2/day fluorouracil (5-FU) IV on days 1 to 5 of each 21-day cycle.
    Measure Participants 283
    Cycle 1, Day 1
    133
    (31)
    Cycle 3, Day 1
    173
    (35)
    Cycle 9, Day 1
    169
    (60)
    13. Secondary Outcome
    Title PK: Minimum Concentration (Cmin) of Ramucirumab
    Description Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab
    Time Frame Cycle 1 Day 1: 1 hour (hr) end of infusion (EOI), Cycle 3 Day 1: 1hr EOI, Cycle 9 Day 1: 1 hr EOI

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received ramucirumab and had evaluable PK data
    Arm/Group Title Ramucirumab + Cisplatin + Capecitabine
    Arm/Group Description 8 milligrams/kilogram (mg/kg) ramucirumab given intravenously (IV) on days 1 and 8 in combination with 80 mg/square meter (m^2) cisplatin given IV on day 1 of each 21-day cycle (for up to 6 cycles) and 1000 mg/m^2 capecitabine given orally twice a day on days 1 through 14. Participants that were unable to take capecitabine will be given 800 mg/m^2/day fluorouracil (5-FU) IV on days 1 to 5 of each 21-day cycle.
    Measure Participants 268
    Cycle 1, Day 8
    40.7
    (35)
    Cycle 2, Day 1
    35.7
    (56)
    Cycle 3, Day 1
    51.2
    (47)
    Cycle 5, Day 1
    69.7
    (52)
    Cycle 9, Day 1
    77.6
    (98)

    Adverse Events

    Time Frame Baseline Up To 5.6 Years
    Adverse Event Reporting Description All participants who received at least one dose of study drug.
    Arm/Group Title LY3009806+Capecitabine+Cisplatin Placebo+Capecitabine+Cisplatin
    Arm/Group Description 8 milligrams/kilogram (mg/kg) ramucirumab given intravenously (IV) on days 1 and 8 in combination with 80 mg/square meter (m^2) cisplatin given IV on day 1 of each 21-day cycle (for up to 6 cycles) and 1000 mg/m^2 capecitabine given orally twice a day on days 1 through 14. Participants that were unable to take capecitabine will be given 800 mg/m^2/day fluorouracil (5-FU) IV on days 1 to 5 of each 21-day cycle. Placebo for blinding given IV on days 1 and 8 in combination with 80 mg/m^2 cisplatin given IV on day 1 of each 21-day cycle (for up to 6 cycles) and 1000 mg/m^2 capecitabine given orally twice a day on days 1 through 14. Participants that were unable to take capecitabine will be given 800 mg/m^2/day 5-FU IV on days 1 to 5 of each 21-day cycle.
    All Cause Mortality
    LY3009806+Capecitabine+Cisplatin Placebo+Capecitabine+Cisplatin
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    LY3009806+Capecitabine+Cisplatin Placebo+Capecitabine+Cisplatin
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 161/323 (49.8%) 150/315 (47.6%)
    Blood and lymphatic system disorders
    Anaemia 11/323 (3.4%) 11 11/315 (3.5%) 16
    Blood loss anaemia 0/323 (0%) 0 1/315 (0.3%) 3
    Bone marrow failure 1/323 (0.3%) 2 1/315 (0.3%) 1
    Febrile neutropenia 5/323 (1.5%) 5 11/315 (3.5%) 13
    Haemolytic anaemia 0/323 (0%) 0 1/315 (0.3%) 1
    Leukopenia 0/323 (0%) 0 1/315 (0.3%) 1
    Neutropenia 2/323 (0.6%) 6 8/315 (2.5%) 9
    Pancytopenia 1/323 (0.3%) 1 1/315 (0.3%) 1
    Thrombocytopenia 2/323 (0.6%) 2 1/315 (0.3%) 1
    Cardiac disorders
    Acute myocardial infarction 1/323 (0.3%) 1 1/315 (0.3%) 1
    Angina pectoris 1/323 (0.3%) 1 0/315 (0%) 0
    Arrhythmia 1/323 (0.3%) 1 0/315 (0%) 0
    Arrhythmia supraventricular 1/323 (0.3%) 1 0/315 (0%) 0
    Atrial fibrillation 2/323 (0.6%) 2 2/315 (0.6%) 2
    Atrioventricular block complete 0/323 (0%) 0 1/315 (0.3%) 1
    Cardiac arrest 1/323 (0.3%) 1 0/315 (0%) 0
    Cardiac disorder 1/323 (0.3%) 1 0/315 (0%) 0
    Cardiogenic shock 1/323 (0.3%) 1 0/315 (0%) 0
    Pericardial effusion 0/323 (0%) 0 2/315 (0.6%) 2
    Sinus bradycardia 1/323 (0.3%) 1 0/315 (0%) 0
    Sinus node dysfunction 1/323 (0.3%) 1 0/315 (0%) 0
    Supraventricular extrasystoles 0/323 (0%) 0 1/315 (0.3%) 1
    Tachycardia 1/323 (0.3%) 1 0/315 (0%) 0
    Eye disorders
    Retinal vein thrombosis 0/323 (0%) 0 1/315 (0.3%) 1
    Gastrointestinal disorders
    Abdominal distension 1/323 (0.3%) 1 0/315 (0%) 0
    Abdominal pain 13/323 (4%) 16 7/315 (2.2%) 10
    Abdominal pain upper 0/323 (0%) 0 1/315 (0.3%) 1
    Abdominal rigidity 1/323 (0.3%) 1 0/315 (0%) 0
    Acute abdomen 1/323 (0.3%) 1 0/315 (0%) 0
    Ascites 3/323 (0.9%) 3 2/315 (0.6%) 2
    Colitis 1/323 (0.3%) 1 3/315 (1%) 3
    Constipation 3/323 (0.9%) 5 0/315 (0%) 0
    Diarrhoea 11/323 (3.4%) 13 19/315 (6%) 20
    Dysphagia 8/323 (2.5%) 9 7/315 (2.2%) 8
    Enteritis 0/323 (0%) 0 1/315 (0.3%) 1
    Enterocolitis 2/323 (0.6%) 2 0/315 (0%) 0
    Enterocutaneous fistula 1/323 (0.3%) 1 0/315 (0%) 0
    Erosive oesophagitis 0/323 (0%) 0 1/315 (0.3%) 1
    Gastric haemorrhage 5/323 (1.5%) 5 3/315 (1%) 3
    Gastric perforation 9/323 (2.8%) 9 1/315 (0.3%) 1
    Gastric ulcer haemorrhage 1/323 (0.3%) 1 0/315 (0%) 0
    Gastric ulcer perforation 1/323 (0.3%) 1 0/315 (0%) 0
    Gastrointestinal haemorrhage 1/323 (0.3%) 1 2/315 (0.6%) 2
    Gastrointestinal obstruction 0/323 (0%) 0 1/315 (0.3%) 2
    Haematemesis 1/323 (0.3%) 1 3/315 (1%) 3
    Haematochezia 1/323 (0.3%) 1 0/315 (0%) 0
    Hiatus hernia 0/323 (0%) 0 1/315 (0.3%) 1
    Ileus 2/323 (0.6%) 3 3/315 (1%) 5
    Ileus paralytic 1/323 (0.3%) 1 0/315 (0%) 0
    Impaired gastric emptying 0/323 (0%) 0 1/315 (0.3%) 1
    Inguinal hernia 1/323 (0.3%) 1 1/315 (0.3%) 1
    Intestinal obstruction 4/323 (1.2%) 7 0/315 (0%) 0
    Intestinal perforation 1/323 (0.3%) 1 0/315 (0%) 0
    Intra-abdominal haemorrhage 0/323 (0%) 0 1/315 (0.3%) 1
    Large intestinal stenosis 1/323 (0.3%) 1 0/315 (0%) 0
    Large intestine perforation 1/323 (0.3%) 1 0/315 (0%) 0
    Lower gastrointestinal haemorrhage 1/323 (0.3%) 1 0/315 (0%) 0
    Melaena 0/323 (0%) 0 2/315 (0.6%) 3
    Nausea 5/323 (1.5%) 5 8/315 (2.5%) 10
    Obstruction gastric 0/323 (0%) 0 1/315 (0.3%) 1
    Oesophageal fistula 1/323 (0.3%) 1 0/315 (0%) 0
    Oesophageal haemorrhage 1/323 (0.3%) 1 0/315 (0%) 0
    Oesophageal stenosis 1/323 (0.3%) 1 2/315 (0.6%) 2
    Pneumoperitoneum 1/323 (0.3%) 1 0/315 (0%) 0
    Rectal haemorrhage 1/323 (0.3%) 1 0/315 (0%) 0
    Small intestinal obstruction 0/323 (0%) 0 2/315 (0.6%) 3
    Small intestinal perforation 1/323 (0.3%) 1 1/315 (0.3%) 1
    Stomatitis 4/323 (1.2%) 4 2/315 (0.6%) 2
    Subileus 4/323 (1.2%) 5 0/315 (0%) 0
    Upper gastrointestinal haemorrhage 3/323 (0.9%) 5 1/315 (0.3%) 2
    Vomiting 14/323 (4.3%) 15 22/315 (7%) 27
    General disorders
    Asthenia 3/323 (0.9%) 3 2/315 (0.6%) 2
    Complication associated with device 1/323 (0.3%) 1 0/315 (0%) 0
    Death 1/323 (0.3%) 1 0/315 (0%) 0
    Device occlusion 0/323 (0%) 0 2/315 (0.6%) 2
    Fall 2/323 (0.6%) 2 1/315 (0.3%) 1
    Fatigue 1/323 (0.3%) 1 3/315 (1%) 3
    General physical health deterioration 6/323 (1.9%) 7 5/315 (1.6%) 5
    Heparin-induced thrombocytopenia 1/323 (0.3%) 1 0/315 (0%) 0
    Impaired healing 1/323 (0.3%) 1 0/315 (0%) 0
    Infusion related reaction 1/323 (0.3%) 1 0/315 (0%) 0
    Malaise 3/323 (0.9%) 4 1/315 (0.3%) 1
    Mucosal inflammation 1/323 (0.3%) 1 2/315 (0.6%) 2
    Multiple organ dysfunction syndrome 0/323 (0%) 0 3/315 (1%) 4
    Non-cardiac chest pain 1/323 (0.3%) 1 2/315 (0.6%) 2
    Pain 0/323 (0%) 0 1/315 (0.3%) 2
    Pyrexia 2/323 (0.6%) 2 12/315 (3.8%) 12
    Sudden death 1/323 (0.3%) 1 0/315 (0%) 0
    Hepatobiliary disorders
    Bile duct obstruction 0/323 (0%) 0 1/315 (0.3%) 1
    Cholangitis 0/323 (0%) 0 2/315 (0.6%) 3
    Hepatic failure 0/323 (0%) 0 3/315 (1%) 3
    Hyperbilirubinaemia 2/323 (0.6%) 2 0/315 (0%) 0
    Immune system disorders
    Hypersensitivity 1/323 (0.3%) 1 0/315 (0%) 0
    Infections and infestations
    Biliary tract infection 1/323 (0.3%) 1 0/315 (0%) 0
    Cellulitis 1/323 (0.3%) 1 1/315 (0.3%) 1
    Cystitis bacterial 1/323 (0.3%) 1 0/315 (0%) 0
    Device related infection 1/323 (0.3%) 1 1/315 (0.3%) 1
    Device related sepsis 0/323 (0%) 0 2/315 (0.6%) 2
    Enterocolitis infectious 0/323 (0%) 0 1/315 (0.3%) 1
    Gastroenteritis 0/323 (0%) 0 1/315 (0.3%) 1
    Infection 2/323 (0.6%) 2 0/315 (0%) 0
    Lower respiratory tract infection 0/323 (0%) 0 1/315 (0.3%) 1
    Periodontitis 1/323 (0.3%) 1 0/315 (0%) 0
    Periorbital infection 0/323 (0%) 0 1/315 (0.3%) 1
    Peritonitis 1/323 (0.3%) 1 0/315 (0%) 0
    Pharyngitis 0/323 (0%) 0 1/315 (0.3%) 1
    Pneumonia 5/323 (1.5%) 5 7/315 (2.2%) 7
    Pneumonia bacterial 0/323 (0%) 0 1/315 (0.3%) 2
    Pseudomembranous colitis 0/323 (0%) 0 1/315 (0.3%) 1
    Pseudomonas infection 0/323 (0%) 0 1/315 (0.3%) 1
    Pyelonephritis 1/323 (0.3%) 1 1/315 (0.3%) 1
    Sepsis 4/323 (1.2%) 5 5/315 (1.6%) 5
    Septic shock 1/323 (0.3%) 1 2/315 (0.6%) 2
    Vascular device infection 1/323 (0.3%) 1 0/315 (0%) 0
    Injury, poisoning and procedural complications
    Accidental overdose 0/323 (0%) 0 1/315 (0.3%) 1
    Device dislocation 1/323 (0.3%) 1 3/315 (1%) 3
    Gastrointestinal stoma complication 0/323 (0%) 0 1/315 (0.3%) 1
    Skin laceration 1/323 (0.3%) 1 0/315 (0%) 0
    Vascular access complication 1/323 (0.3%) 1 0/315 (0%) 0
    Investigations
    Alanine aminotransferase increased 0/323 (0%) 0 2/315 (0.6%) 2
    Aspartate aminotransferase increased 0/323 (0%) 0 1/315 (0.3%) 2
    Blood bilirubin increased 0/323 (0%) 0 2/315 (0.6%) 2
    Blood creatinine increased 2/323 (0.6%) 2 0/315 (0%) 0
    Blood potassium decreased 0/323 (0%) 0 1/315 (0.3%) 1
    Body temperature increased 0/323 (0%) 0 1/315 (0.3%) 1
    Creatinine renal clearance decreased 0/323 (0%) 0 1/315 (0.3%) 1
    Neutrophil count decreased 2/323 (0.6%) 2 2/315 (0.6%) 2
    Platelet count decreased 2/323 (0.6%) 2 1/315 (0.3%) 1
    Weight decreased 0/323 (0%) 0 1/315 (0.3%) 1
    White blood cell count decreased 1/323 (0.3%) 1 0/315 (0%) 0
    Metabolism and nutrition disorders
    Cachexia 1/323 (0.3%) 1 0/315 (0%) 0
    Decreased appetite 5/323 (1.5%) 6 3/315 (1%) 3
    Dehydration 7/323 (2.2%) 9 9/315 (2.9%) 9
    Hypercalcaemia 0/323 (0%) 0 1/315 (0.3%) 2
    Hyperglycaemia 1/323 (0.3%) 1 2/315 (0.6%) 2
    Hyperkalaemia 0/323 (0%) 0 1/315 (0.3%) 3
    Hypocalcaemia 0/323 (0%) 0 2/315 (0.6%) 3
    Hypokalaemia 1/323 (0.3%) 1 4/315 (1.3%) 5
    Hypomagnesaemia 1/323 (0.3%) 1 1/315 (0.3%) 3
    Hyponatraemia 6/323 (1.9%) 10 2/315 (0.6%) 2
    Hypophosphataemia 0/323 (0%) 0 1/315 (0.3%) 1
    Malnutrition 1/323 (0.3%) 1 1/315 (0.3%) 1
    Musculoskeletal and connective tissue disorders
    Back pain 1/323 (0.3%) 1 0/315 (0%) 0
    Osteonecrosis 1/323 (0.3%) 1 0/315 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Colorectal cancer 1/323 (0.3%) 1 0/315 (0%) 0
    Malignant pleural effusion 0/323 (0%) 0 2/315 (0.6%) 2
    Metastases to peritoneum 1/323 (0.3%) 1 0/315 (0%) 0
    Tumour associated fever 0/323 (0%) 0 1/315 (0.3%) 1
    Tumour haemorrhage 1/323 (0.3%) 1 1/315 (0.3%) 2
    Nervous system disorders
    Cerebral infarction 1/323 (0.3%) 1 1/315 (0.3%) 1
    Cerebrovascular accident 1/323 (0.3%) 1 3/315 (1%) 3
    Cognitive disorder 0/323 (0%) 0 1/315 (0.3%) 1
    Dizziness 1/323 (0.3%) 1 0/315 (0%) 0
    Haemorrhage intracranial 0/323 (0%) 0 1/315 (0.3%) 1
    Ischaemic stroke 1/323 (0.3%) 1 1/315 (0.3%) 1
    Nervous system disorder 1/323 (0.3%) 1 0/315 (0%) 0
    Presyncope 1/323 (0.3%) 2 0/315 (0%) 0
    Syncope 2/323 (0.6%) 2 1/315 (0.3%) 1
    Psychiatric disorders
    Confusional state 1/323 (0.3%) 1 2/315 (0.6%) 2
    Delirium 1/323 (0.3%) 2 1/315 (0.3%) 1
    Depression 0/323 (0%) 0 1/315 (0.3%) 1
    Renal and urinary disorders
    Acute kidney injury 10/323 (3.1%) 10 8/315 (2.5%) 13
    Hydronephrosis 0/323 (0%) 0 1/315 (0.3%) 1
    Nephritis 1/323 (0.3%) 1 0/315 (0%) 0
    Nephropathy 0/323 (0%) 0 1/315 (0.3%) 1
    Proteinuria 0/323 (0%) 0 1/315 (0.3%) 1
    Pyelocaliectasis 0/323 (0%) 0 1/315 (0.3%) 1
    Renal colic 0/323 (0%) 0 1/315 (0.3%) 1
    Renal failure 0/323 (0%) 0 2/315 (0.6%) 2
    Renal impairment 1/323 (0.3%) 1 0/315 (0%) 0
    Urinary retention 1/323 (0.3%) 1 0/315 (0%) 0
    Urinary tract obstruction 1/323 (0.3%) 1 1/315 (0.3%) 1
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory distress syndrome 0/323 (0%) 0 2/315 (0.6%) 2
    Dyspnoea 5/323 (1.5%) 6 2/315 (0.6%) 2
    Hiccups 1/323 (0.3%) 1 0/315 (0%) 0
    Hypoxia 0/323 (0%) 0 1/315 (0.3%) 1
    Lung disorder 0/323 (0%) 0 1/315 (0.3%) 1
    Pleural effusion 0/323 (0%) 0 3/315 (1%) 3
    Pneumonia aspiration 1/323 (0.3%) 1 0/315 (0%) 0
    Pneumonitis 0/323 (0%) 0 2/315 (0.6%) 2
    Pneumothorax 1/323 (0.3%) 1 1/315 (0.3%) 1
    Pneumothorax spontaneous 1/323 (0.3%) 1 0/315 (0%) 0
    Pulmonary embolism 7/323 (2.2%) 7 9/315 (2.9%) 9
    Respiratory failure 1/323 (0.3%) 1 0/315 (0%) 0
    Skin and subcutaneous tissue disorders
    Dermatomyositis 0/323 (0%) 0 1/315 (0.3%) 1
    Palmar-plantar erythrodysaesthesia syndrome 2/323 (0.6%) 3 0/315 (0%) 0
    Skin disorder 0/323 (0%) 0 1/315 (0.3%) 1
    Vascular disorders
    Arterial thrombosis 0/323 (0%) 0 1/315 (0.3%) 1
    Brachiocephalic vein thrombosis 0/323 (0%) 0 1/315 (0.3%) 1
    Circulatory collapse 1/323 (0.3%) 1 0/315 (0%) 0
    Deep vein thrombosis 5/323 (1.5%) 5 3/315 (1%) 3
    Embolism arterial 1/323 (0.3%) 1 0/315 (0%) 0
    Embolism venous 0/323 (0%) 0 1/315 (0.3%) 1
    Hypertension 2/323 (0.6%) 2 0/315 (0%) 0
    Hypotension 2/323 (0.6%) 2 3/315 (1%) 3
    Hypovolaemic shock 1/323 (0.3%) 1 1/315 (0.3%) 1
    Orthostatic hypotension 1/323 (0.3%) 1 0/315 (0%) 0
    Phlebitis deep 1/323 (0.3%) 1 0/315 (0%) 0
    Subclavian vein thrombosis 0/323 (0%) 0 1/315 (0.3%) 2
    Thrombophlebitis superficial 0/323 (0%) 0 1/315 (0.3%) 1
    Venous thrombosis 1/323 (0.3%) 1 0/315 (0%) 0
    Venous thrombosis limb 0/323 (0%) 0 1/315 (0.3%) 1
    Other (Not Including Serious) Adverse Events
    LY3009806+Capecitabine+Cisplatin Placebo+Capecitabine+Cisplatin
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 315/323 (97.5%) 304/315 (96.5%)
    Blood and lymphatic system disorders
    Anaemia 104/323 (32.2%) 276 114/315 (36.2%) 289
    Neutropenia 71/323 (22%) 218 74/315 (23.5%) 133
    Thrombocytopenia 41/323 (12.7%) 106 26/315 (8.3%) 51
    Ear and labyrinth disorders
    Tinnitus 23/323 (7.1%) 26 27/315 (8.6%) 32
    Gastrointestinal disorders
    Abdominal pain 52/323 (16.1%) 80 51/315 (16.2%) 69
    Abdominal pain upper 22/323 (6.8%) 27 15/315 (4.8%) 22
    Constipation 104/323 (32.2%) 161 78/315 (24.8%) 107
    Diarrhoea 108/323 (33.4%) 175 107/315 (34%) 175
    Dyspepsia 19/323 (5.9%) 20 12/315 (3.8%) 14
    Dysphagia 21/323 (6.5%) 33 17/315 (5.4%) 23
    Nausea 205/323 (63.5%) 459 186/315 (59%) 444
    Stomatitis 67/323 (20.7%) 110 39/315 (12.4%) 64
    Vomiting 134/323 (41.5%) 249 117/315 (37.1%) 217
    General disorders
    Asthenia 44/323 (13.6%) 133 40/315 (12.7%) 101
    Fatigue 153/323 (47.4%) 316 145/315 (46%) 309
    Mucosal inflammation 20/323 (6.2%) 31 17/315 (5.4%) 41
    Oedema peripheral 45/323 (13.9%) 65 33/315 (10.5%) 46
    Pyrexia 28/323 (8.7%) 37 40/315 (12.7%) 56
    Infections and infestations
    Upper respiratory tract infection 8/323 (2.5%) 11 17/315 (5.4%) 18
    Investigations
    Alanine aminotransferase increased 19/323 (5.9%) 29 10/315 (3.2%) 15
    Aspartate aminotransferase increased 20/323 (6.2%) 25 12/315 (3.8%) 17
    Blood creatinine increased 31/323 (9.6%) 60 28/315 (8.9%) 41
    Neutrophil count decreased 103/323 (31.9%) 295 92/315 (29.2%) 263
    Platelet count decreased 72/323 (22.3%) 254 33/315 (10.5%) 75
    Weight decreased 54/323 (16.7%) 72 37/315 (11.7%) 56
    White blood cell count decreased 37/323 (11.5%) 118 32/315 (10.2%) 109
    Metabolism and nutrition disorders
    Decreased appetite 130/323 (40.2%) 245 100/315 (31.7%) 190
    Dehydration 19/323 (5.9%) 25 25/315 (7.9%) 30
    Hypoalbuminaemia 17/323 (5.3%) 28 13/315 (4.1%) 21
    Hypocalcaemia 20/323 (6.2%) 23 11/315 (3.5%) 21
    Hypokalaemia 36/323 (11.1%) 51 40/315 (12.7%) 68
    Hypomagnesaemia 36/323 (11.1%) 47 45/315 (14.3%) 97
    Hyponatraemia 18/323 (5.6%) 30 17/315 (5.4%) 21
    Musculoskeletal and connective tissue disorders
    Back pain 28/323 (8.7%) 33 16/315 (5.1%) 20
    Nervous system disorders
    Dizziness 36/323 (11.1%) 42 35/315 (11.1%) 52
    Dysgeusia 34/323 (10.5%) 38 27/315 (8.6%) 31
    Headache 43/323 (13.3%) 57 27/315 (8.6%) 36
    Neuropathy peripheral 20/323 (6.2%) 30 8/315 (2.5%) 9
    Peripheral sensory neuropathy 39/323 (12.1%) 62 31/315 (9.8%) 41
    Psychiatric disorders
    Insomnia 27/323 (8.4%) 29 25/315 (7.9%) 27
    Renal and urinary disorders
    Proteinuria 64/323 (19.8%) 156 36/315 (11.4%) 60
    Respiratory, thoracic and mediastinal disorders
    Cough 25/323 (7.7%) 29 18/315 (5.7%) 18
    Dyspnoea 36/323 (11.1%) 49 21/315 (6.7%) 26
    Epistaxis 48/323 (14.9%) 76 14/315 (4.4%) 19
    Hiccups 36/323 (11.1%) 63 33/315 (10.5%) 46
    Skin and subcutaneous tissue disorders
    Alopecia 19/323 (5.9%) 21 16/315 (5.1%) 20
    Dry skin 20/323 (6.2%) 23 16/315 (5.1%) 17
    Palmar-plantar erythrodysaesthesia syndrome 99/323 (30.7%) 248 63/315 (20%) 121
    Skin hyperpigmentation 18/323 (5.6%) 18 10/315 (3.2%) 10
    Vascular disorders
    Embolism venous 13/323 (4%) 13 17/315 (5.4%) 17
    Hypertension 70/323 (21.7%) 152 23/315 (7.3%) 30

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title Chief Medical Officer
    Organization Eli Lilly and Company
    Phone 800-545-5979
    Email ClinicalTrials.gov@lilly.com
    Responsible Party:
    Eli Lilly and Company
    ClinicalTrials.gov Identifier:
    NCT02314117
    Other Study ID Numbers:
    • 15372
    • I4T-MC-JVCU
    • 2014-002240-40
    First Posted:
    Dec 10, 2014
    Last Update Posted:
    Aug 26, 2021
    Last Verified:
    Jul 1, 2021