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A Phase 2 Study of Ramucirumab (LY3009806) in Participants With Gastric or Gastroesophageal Junction (GEJ) Cancer

Sponsor
Eli Lilly and Company (Industry)
Overall Status
Completed
CT.gov ID
NCT02443883
Collaborator
(none)
164
Enrollment
45
Locations
4
Arms
46.9
Actual Duration (Months)
3.6
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The main purpose of this study was to evaluate the safety and pharmacokinetics of administering various dose regimens of ramucirumab in participants with advanced gastric cancer whose disease has progressed during or following prior chemotherapy.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
164 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Randomized Phase 2 Trial Evaluating Pharmacokinetics and Safety of Four Ramucirumab Dosing Regimens in Second-Line Gastric or Gastroesophageal Junction Adenocarcinoma
Actual Study Start Date :
Jul 7, 2015
Actual Primary Completion Date :
Nov 18, 2016
Actual Study Completion Date :
Jun 5, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: Ramucirumab Regimen 1

Standard dose of 8 milligram per kilogram (mg/kg) ramucirumab given intravenously (IV) on day 1 and day 15 of each cycle (28-day cycle) until discontinuation criteria are met.

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

    		•
    Experimental: Ramucirumab Regimen 2

    Experimental dose of 12 mg/kg ramucirumab given IV on day 1 and day 15 of each cycle (28-day cycle) until discontinuation criteria are met.

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

    		•
    Experimental: Ramucirumab Regimen 3

    Experimental dose of 6 mg/kg ramucirumab given IV on day 1, 8, 15 and 22 of each cycle (28-day cycle) until discontinuation criteria are met.

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

    		•
    Experimental: Ramucirumab Regimen 4

    Experimental dose of 8 mg/kg ramucirumab given IV on day 1 and day 8 of each cycle (21-day cycle) until discontinuation criteria are met.

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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab [Day 29, 43, 71 and 85: predose]

      The Cmin is the minimum observed serum concentration of ramucirumab.

    Secondary Outcome Measures

    1. Immunogenicity: Number of Participants With Anti-Ramucirumab Antibodies [Predose Cycle 1 Through Short Term Follow Up (Up to 5 Months)]

      Number of participants with positive treatment emergent anti-ramucirumab antibodies was summarized by treatment group. A treatment-emergent anti-drug antibodies (TEADA) sample was defined as: a post treatment sample with at least a 4-fold increase in titer from pre treatment sample; or 1:20 post treatment titer for participants that had no detectable ADA titer at baseline.

    2. Rate of Progression Free Survival (PFS) at the First 6-Week Tumor Assessment [Baseline until the first 6-week tumor assessment]

      PFS defined as the time from first day of therapy to first evidence of disease progression per response evaluation criteria in solid tumors version 1.1 (RECIST v1.1) or death from any cause up to the first 6-week tumor assessment. Progressive Disease (PD) is at least 20% increase in sum of diameters of target lesions,taking as reference smallest sum on study and absolute increase of at least 5 mm.Appearance of 1 or more new lesions was also considered progression. Nontarget PD is unequivocal progression of existing nontarget lesions.Appearance of 1 or more new nontarget lesions was also considered PD.Participants with no baseline disease assessment: PFS time was censored at the randomization date,regardless of whether or not objectively determined disease progression or death has been observed.

    Eligibility Criteria

    Criteria

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

    • The participant has a histopathologically or cytologically confirmed diagnosis of gastric or gastroesophageal junction (GEJ).

    • The participant has documented disease progression during or within 4 months after the last dose of first-line chemotherapy for metastatic disease, or during or within 6 months after the last dose of neoadjuvant or adjuvant therapy.

    • The participant received combination chemotherapy prior to disease progression.

    • Prior chemotherapy regimens must include a platinum and/or a fluoropyrimidine component and must not include a taxane or antiangiogenic agent.

    • The participant has metastatic disease or locally advanced disease that is measurable or nonmeasurable, but is evaluable disease by radiological imaging per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1).

    • Patients are eligible if they are considered not appropriate, for whatever reason, for treatment with ramucirumab in combination with paclitaxel.

    • The participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

    • The participant has adequate organ function, including:

    • Total bilirubin 1.5 × the upper limit of institutional normal (ULN) and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) 3 × ULN. If the liver has tumor involvement, AST and ALT <5 × ULN are acceptable.

    • Serum creatinine 1.5 × ULN or calculated creatinine clearance (per the Cockcroft-Gault formula or equivalent and/or 24-hour urine collection) 60 milliliters/minute (mL/min).

    • Urinary protein is <2+ on dipstick or routine urinalysis.

    • Absolute neutrophil count 1.5 × 109/Liter (L), platelets 100 × 109/L, and hemoglobin 9 g/deciliter (dL) (5.58 millimoles/Liter).

    • International normalized ratio 1.5 × ULN or prothrombin time 5 seconds above ULN.

    • Partial thromboplastin time 5 seconds above ULN.

    • The participant has an estimated life expectancy of 12 weeks in the judgment of the investigator.

    • The participant, if female and of child-bearing potential, must have a negative serum or urine pregnancy test within 7 days prior to randomization.

    Exclusion Criteria:

    • The participant has squamous cell or undifferentiated gastric cancer.

    • The participant is receiving chronic therapy with any of the following within 7 days prior to randomization:

    • Nonsteroidal anti-inflammatory agents (NSAIDs; such as indomethacin, ibuprofen, naproxen, or similar agents), or

    • Other anti-platelet agents (such as clopidogrel, ticlopidine, dipyridamole, or anagrelide). Aspirin use at doses up to 325 milligrams (mg)/day is permitted.

    • The participant received radiotherapy within 14 days prior to randomization.

    • The participant received >1 line of prior therapy for the treatment of locally advanced and unresectable or metastatic gastric or GEJ (Siewert Types I-III) adenocarcinoma.

    • The participant received previous treatment with agents targeting the vascular endothelial growth factor (VEGF)/VEGF receptor 2 signaling pathway.

    • The participant has documented brain metastases, leptomeningeal disease, or uncontrolled spinal cord compression.

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

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

    • The participant has uncontrolled hypertension, as defined in Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0, prior to initiating study treatment, despite antihypertensive intervention.

    • The participant underwent major surgery within 28 days prior to randomization or central venous access device placement within 7 days prior to randomization.

    • The participant has a history of gastrointestinal perforation or fistula within 6 months prior to randomization.

    • The participant has any condition (for example, psychological, geographical, or medical) that does not permit compliance with the study and follow-up procedures or suggests that the participant is, in the investigator's opinion, not an appropriate candidate for the study.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Arizona Clinical Research Center Tucson Arizona United States 85715
    2 USC Norris Cancer Hospital Los Angeles California United States 90033
    3 Carolinas Medical Center Charlotte North Carolina United States 28204
    4 Oklahoma Cancer Specialists & Research Institute, LLC Tulsa Oklahoma United States 74146
    5 University of Texas MD Anderson Cancer Center Houston Texas United States 77030
    6 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. Buenos Aires Argentina 1025
    7 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 2000
    8 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. San Miguel de Tucumán Argentina T4000IAK
    9 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 Argentina 8500
    10 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. Adelaide Australia 5000
    11 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. Kingswood Australia 2747
    12 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. Melbourne Australia 3144
    13 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. Nedlands Australia 6009
    14 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. Brest France 29609
    15 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. Creteil France 94010
    16 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. Dijon France 21079
    17 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. Lyon France 69437
    18 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. Paris France 75012
    19 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. Paris France 75013
    20 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. Budapest Hungary 1125
    21 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
    22 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. Auckland New Zealand 1023
    23 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. Christchurch New Zealand 8011
    24 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. Gdansk Poland 80-219
    25 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. Lodz Poland 90-242
    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. Poznan Poland 61-485
    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. Warszawa Poland 04-125
    28 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 Baia Mare Romania 430031
    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 Cluj-Napoca Romania 400058
    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. Craiova Romania 200347
    31 Arkhangelsk Regional Clinical Oncology Dispensary Arkhangelsk Russian Federation 163045
    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. Kursk Russian Federation 305035
    33 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. Moscow Russian Federation 115478
    34 Leningrad regional clinical hospital St. Petersburg Russian Federation 194291
    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 Bratislava Slovakia 833 10
    36 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 Kosice Slovakia 041-90
    37 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. Edirne Turkey 22030
    38 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. Fatih Turkey 34093
    39 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. Pendik Turkey 34668
    40 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. Yüregir Turkey 1250
    41 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. Cardiff United Kingdom CF14 2TL
    42 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. Exeter United Kingdom EX2 5DW
    43 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. Leeds United Kingdom LS9 7TF
    44 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. Manchester United Kingdom M20 4BX
    45 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. Wolverhampton United Kingdom WV10 0QP

    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

    Publications

    None provided.
    Responsible Party:
    Eli Lilly and Company
    ClinicalTrials.gov Identifier:
    NCT02443883
    Other Study ID Numbers:
    • 15608
    • I4T-MC-JVDB
    • 2014-003791-23
    First Posted:
    May 14, 2015
    Last Update Posted:
    Jun 29, 2020
    Last Verified:
    Jul 1, 2019
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Keywords provided by Eli Lilly and Company
    stomach cancer
    Additional relevant MeSH terms:
    Adenocarcinoma
    Esophageal Neoplasms
    Ramucirumab

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail Study completion was defined as death due to any cause or disease progression.
    Arm/Group Title Ramucirumab Regimen 1 Ramucirumab Regimen 2 Ramucirumab Regimen 3 Ramucirumab Regimen 4
    Arm/Group Description Ramucirumab (8milligram per kilogram [mg/kg]) given intravenously (IV) on day 1 and day 15 of each cycle (28-day cycle) until discontinuation criteria are met. Ramucirumab (12 mg/kg) given IV on day 1 and day 15 of each cycle (28-day cycle) until discontinuation criteria are met. Ramucirumab (6 mg/kg) given IV on day 1, 8, 15 and 22 of each cycle (28-day cycle) until discontinuation criteria are met. Ramucirumab (8 mg/kg) given IV on day 1 and day 8 of each cycle (21-day cycle) until discontinuation criteria are met.
    Period Title: Overall Study
    STARTED 40 42 41 41
    Received at Least One Dose of Study Drug 38 42 41 40
    COMPLETED 34 38 40 36
    NOT COMPLETED 6 4 1 5

    Baseline Characteristics

    Arm/Group Title Ramucirumab Regimen 1 Ramucirumab Regimen 2 Ramucirumab Regimen 3 Ramucirumab Regimen 4 Total
    Arm/Group Description Ramucirumab (8 mg/kg) given IV on day 1 and day 15 of each cycle (28-day cycle) until discontinuation criteria are met. Ramucirumab (12 mg/kg) given IV on day 1 and day 15 of each cycle (28-day cycle) until discontinuation criteria are met. Ramucirumab (6 mg/kg) given IV on day 1, 8, 15 and 22 of each cycle (28-day cycle) until discontinuation criteria are met. Ramucirumab (8 mg/kg) given IV on day 1 and day 8 of each cycle (21-day cycle) until discontinuation criteria are met. Total of all reporting groups
    Overall Participants 40 42 41 41 164
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    58.5
    (14.0)
    58.7
    (10.4)
    60.5
    (12.3)
    56.2
    (12.9)
    58.5
    (12.4)
    Sex: Female, Male (Count of Participants)
    Female
    11
    27.5%
    10
    23.8%
    6
    14.6%
    9
    22%
    36
    22%
    Male
    29
    72.5%
    32
    76.2%
    35
    85.4%
    32
    78%
    128
    78%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    6
    15%
    3
    7.1%
    6
    14.6%
    7
    17.1%
    22
    13.4%
    Not Hispanic or Latino
    32
    80%
    37
    88.1%
    33
    80.5%
    32
    78%
    134
    81.7%
    Unknown or Not Reported
    2
    5%
    2
    4.8%
    2
    4.9%
    2
    4.9%
    8
    4.9%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    1
    2.5%
    0
    0%
    0
    0%
    1
    2.4%
    2
    1.2%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    White
    32
    80%
    35
    83.3%
    35
    85.4%
    33
    80.5%
    135
    82.3%
    More than one race
    6
    15%
    7
    16.7%
    5
    12.2%
    6
    14.6%
    24
    14.6%
    Unknown or Not Reported
    1
    2.5%
    0
    0%
    1
    2.4%
    1
    2.4%
    3
    1.8%
    Region of Enrollment (Count of Participants)
    New Zealand
    2
    5%
    1
    2.4%
    1
    2.4%
    3
    7.3%
    7
    4.3%
    Argentina
    5
    12.5%
    1
    2.4%
    2
    4.9%
    6
    14.6%
    14
    8.5%
    Romania
    4
    10%
    6
    14.3%
    10
    24.4%
    7
    17.1%
    27
    16.5%
    Turkey
    3
    7.5%
    4
    9.5%
    2
    4.9%
    2
    4.9%
    11
    6.7%
    Hungary
    0
    0%
    3
    7.1%
    3
    7.3%
    1
    2.4%
    7
    4.3%
    United States
    2
    5%
    3
    7.1%
    2
    4.9%
    1
    2.4%
    8
    4.9%
    Poland
    6
    15%
    6
    14.3%
    7
    17.1%
    5
    12.2%
    24
    14.6%
    United Kingdom
    7
    17.5%
    10
    23.8%
    8
    19.5%
    6
    14.6%
    31
    18.9%
    Slovakia
    3
    7.5%
    1
    2.4%
    2
    4.9%
    1
    2.4%
    7
    4.3%
    Australia
    1
    2.5%
    2
    4.8%
    0
    0%
    5
    12.2%
    8
    4.9%
    France
    1
    2.5%
    1
    2.4%
    2
    4.9%
    1
    2.4%
    5
    3%
    Russia
    6
    15%
    4
    9.5%
    2
    4.9%
    3
    7.3%
    15
    9.1%

    Outcome Measures

    1. Primary Outcome
    Title Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab
    Description The Cmin is the minimum observed serum concentration of ramucirumab.
    Time Frame Day 29, 43, 71 and 85: predose

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least one dose of ramucirumab and had evaluable ramucirumab PK data.
    Arm/Group Title Ramucirumab Regimen 1 Ramucirumab Regimen 2 Ramucirumab Regimen 3 Ramucirumab Regimen 4
    Arm/Group Description Ramucirumab (8 mg/kg) given IV on day 1 and day 15 of each cycle (28-day cycle) until discontinuation criteria are met. Ramucirumab (12 mg/kg) given IV on day 1 and day 15 of each cycle (28-day cycle) until discontinuation criteria are met. Ramucirumab (6 mg/kg) given IV on day 1, 8, 15 and 22 of each cycle (28-day cycle) until discontinuation criteria are met. Ramucirumab (8 mg/kg) given IV on day 1 and day 8 of each cycle (21-day cycle) until discontinuation criteria are met.
    Measure Participants 38 42 41 40
    Day 29
    32.9
    (51)
    59.5
    (60)
    69.3
    (45)
    71.6
    (37)
    Day 43
    47.6
    (36)
    71.0
    (58)
    83.0
    (57)
    57.4
    (44)
    Day 71
    60.4
    (34)
    65.0
    (60)
    122
    (65)
    97.1
    (46)
    Day 85
    64.3
    (40)
    79.4
    (46)
    125
    (56)
    81.6
    (50)
    2. Secondary Outcome
    Title Immunogenicity: Number of Participants With Anti-Ramucirumab Antibodies
    Description Number of participants with positive treatment emergent anti-ramucirumab antibodies was summarized by treatment group. A treatment-emergent anti-drug antibodies (TEADA) sample was defined as: a post treatment sample with at least a 4-fold increase in titer from pre treatment sample; or 1:20 post treatment titer for participants that had no detectable ADA titer at baseline.
    Time Frame Predose Cycle 1 Through Short Term Follow Up (Up to 5 Months)

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least 1 dose of ramucirumab and had evaluable anti-ramucirumab antibody measurement.
    Arm/Group Title Ramucirumab Regimen 1 Ramucirumab Regimen 2 Ramucirumab Regimen 3 Ramucirumab Regimen 4
    Arm/Group Description Ramucirumab (8 mg/kg) given IV on day 1 and day 15 of each cycle (28-day cycle) until discontinuation criteria are met. Ramucirumab (12 mg/kg) given IV on day 1 and day 15 of each cycle (28-day cycle) until discontinuation criteria are met. Ramucirumab (6 mg/kg) given IV on day 1, 8, 15 and 22 of each cycle (28-day cycle) until discontinuation criteria are met. Ramucirumab (8 mg/kg) given IV on day 1 and day 8 of each cycle (21-day cycle) until discontinuation criteria are met.
    Measure Participants 19 26 20 22
    Count of Participants [Participants]
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    3. Secondary Outcome
    Title Rate of Progression Free Survival (PFS) at the First 6-Week Tumor Assessment
    Description PFS defined as the time from first day of therapy to first evidence of disease progression per response evaluation criteria in solid tumors version 1.1 (RECIST v1.1) or death from any cause up to the first 6-week tumor assessment. Progressive Disease (PD) is at least 20% increase in sum of diameters of target lesions,taking as reference smallest sum on study and absolute increase of at least 5 mm.Appearance of 1 or more new lesions was also considered progression. Nontarget PD is unequivocal progression of existing nontarget lesions.Appearance of 1 or more new nontarget lesions was also considered PD.Participants with no baseline disease assessment: PFS time was censored at the randomization date,regardless of whether or not objectively determined disease progression or death has been observed.
    Time Frame Baseline until the first 6-week tumor assessment

    Outcome Measure Data

    Analysis Population Description
    All randomized participants.Censored participants:Ramucirumab Regimen 1 = 8,Ramucirumab Regimen 2 =10,Ramucirumab Regimen 3=8 and Ramucirumab Regimen 4=12. PFS survival rate at the first 6-week assessment was estimated using the Kaplan-Meier method which takes into consideration who were censored prior to 6 weeks.
    Arm/Group Title Ramucirumab Regimen 1 Ramucirumab Regimen 2 Ramucirumab Regimen 3 Ramucirumab Regimen 4
    Arm/Group Description Ramucirumab (8 mg/kg) given IV on day 1 and day 15 of each cycle (28-day cycle) until discontinuation criteria are met. Ramucirumab (12 mg/kg) given IV on day 1 and day 15 of each cycle (28-day cycle) until discontinuation criteria are met. Ramucirumab (6 mg/kg) given IV on day 1, 8, 15 and 22 of each cycle (28-day cycle) until discontinuation criteria are met. Ramucirumab (8 mg/kg) given IV on day 1 and day 8 of each cycle (21-day cycle) until discontinuation criteria are met.
    Measure Participants 40 42 41 41
    Number (95% Confidence Interval) [Percentage of participants]
    43.9
    109.8%
    61.9
    147.4%
    53.0
    129.3%
    51.2
    124.9%

    Adverse Events

    Time Frame Up To 3 Years and 3 Months
    Adverse Event Reporting Description All randomized participants who received at least one dose of study drug.
    Arm/Group Title Ramucirumab Regimen 1 Ramucirumab Regimen 2 Ramucirumab Regimen 3 Ramucirumab Regimen 4
    Arm/Group Description Ramucirumab (8 mg/kg) given IV on day 1 and day 15 of each cycle (28-day cycle) until discontinuation criteria are met. Ramucirumab (12 mg/kg) given IV on day 1 and day 15 of each cycle (28-day cycle) until discontinuation criteria are met. Ramucirumab (6 mg/kg) given IV on day 1, 8, 15 and 22 of each cycle (28-day cycle) until discontinuation criteria are met. Ramucirumab (8 mg/kg) given IV on day 1 and day 8 of each cycle (21-day cycle) until discontinuation criteria are met.
    All Cause Mortality
    Ramucirumab Regimen 1 Ramucirumab Regimen 2 Ramucirumab Regimen 3 Ramucirumab Regimen 4
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Ramucirumab Regimen 1 Ramucirumab Regimen 2 Ramucirumab Regimen 3 Ramucirumab Regimen 4
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 10/38 (26.3%) 11/42 (26.2%) 10/41 (24.4%) 18/40 (45%)
    Blood and lymphatic system disorders
    Anaemia 0/38 (0%) 0 1/42 (2.4%) 1 0/41 (0%) 0 1/40 (2.5%) 1
    Cardiac disorders
    Cardiac arrest 1/38 (2.6%) 1 1/42 (2.4%) 1 0/41 (0%) 0 0/40 (0%) 0
    Cardiac failure congestive 0/38 (0%) 0 0/42 (0%) 0 0/41 (0%) 0 1/40 (2.5%) 1
    Myocardial infarction 0/38 (0%) 0 1/42 (2.4%) 1 0/41 (0%) 0 0/40 (0%) 0
    Gastrointestinal disorders
    Abdominal pain 1/38 (2.6%) 1 2/42 (4.8%) 2 0/41 (0%) 0 2/40 (5%) 2
    Abdominal pain upper 0/38 (0%) 0 0/42 (0%) 0 0/41 (0%) 0 1/40 (2.5%) 1
    Ascites 0/38 (0%) 0 0/42 (0%) 0 0/41 (0%) 0 1/40 (2.5%) 2
    Constipation 0/38 (0%) 0 1/42 (2.4%) 1 0/41 (0%) 0 0/40 (0%) 0
    Diarrhoea 0/38 (0%) 0 1/42 (2.4%) 1 0/41 (0%) 0 0/40 (0%) 0
    Duodenal ulcer haemorrhage 1/38 (2.6%) 1 0/42 (0%) 0 0/41 (0%) 0 0/40 (0%) 0
    Dysphagia 0/38 (0%) 0 1/42 (2.4%) 1 1/41 (2.4%) 1 2/40 (5%) 2
    Gastric haemorrhage 0/38 (0%) 0 0/42 (0%) 0 3/41 (7.3%) 3 0/40 (0%) 0
    Gastric perforation 1/38 (2.6%) 1 0/42 (0%) 0 0/41 (0%) 0 0/40 (0%) 0
    Gastrointestinal haemorrhage 0/38 (0%) 0 0/42 (0%) 0 1/41 (2.4%) 1 1/40 (2.5%) 1
    Haematemesis 0/38 (0%) 0 0/42 (0%) 0 1/41 (2.4%) 1 1/40 (2.5%) 1
    Intestinal perforation 0/38 (0%) 0 0/42 (0%) 0 0/41 (0%) 0 1/40 (2.5%) 1
    Nausea 0/38 (0%) 0 0/42 (0%) 0 0/41 (0%) 0 1/40 (2.5%) 1
    Oesophageal perforation 1/38 (2.6%) 1 0/42 (0%) 0 0/41 (0%) 0 0/40 (0%) 0
    Oesophageal spasm 1/38 (2.6%) 1 0/42 (0%) 0 0/41 (0%) 0 0/40 (0%) 0
    Upper gastrointestinal haemorrhage 0/38 (0%) 0 1/42 (2.4%) 1 1/41 (2.4%) 1 0/40 (0%) 0
    Vomiting 1/38 (2.6%) 1 1/42 (2.4%) 2 0/41 (0%) 0 4/40 (10%) 5
    General disorders
    Asthenia 0/38 (0%) 0 0/42 (0%) 0 0/41 (0%) 0 1/40 (2.5%) 1
    Chest pain 0/38 (0%) 0 1/42 (2.4%) 1 0/41 (0%) 0 0/40 (0%) 0
    Fatigue 0/38 (0%) 0 0/42 (0%) 0 0/41 (0%) 0 1/40 (2.5%) 1
    Non-cardiac chest pain 2/38 (5.3%) 2 0/42 (0%) 0 0/41 (0%) 0 0/40 (0%) 0
    Pain 1/38 (2.6%) 1 0/42 (0%) 0 0/41 (0%) 0 0/40 (0%) 0
    Pyrexia 2/38 (5.3%) 3 0/42 (0%) 0 0/41 (0%) 0 0/40 (0%) 0
    Sudden death 0/38 (0%) 0 0/42 (0%) 0 1/41 (2.4%) 1 0/40 (0%) 0
    Hepatobiliary disorders
    Cholangitis 0/38 (0%) 0 0/42 (0%) 0 1/41 (2.4%) 1 0/40 (0%) 0
    Hepatic failure 0/38 (0%) 0 0/42 (0%) 0 0/41 (0%) 0 1/40 (2.5%) 1
    Infections and infestations
    Biliary sepsis 0/38 (0%) 0 1/42 (2.4%) 1 0/41 (0%) 0 0/40 (0%) 0
    Device related infection 1/38 (2.6%) 1 1/42 (2.4%) 1 0/41 (0%) 0 0/40 (0%) 0
    Lower respiratory tract infection 0/38 (0%) 0 0/42 (0%) 0 0/41 (0%) 0 1/40 (2.5%) 1
    Pneumonia 0/38 (0%) 0 2/42 (4.8%) 3 0/41 (0%) 0 1/40 (2.5%) 1
    Sepsis 0/38 (0%) 0 0/42 (0%) 0 0/41 (0%) 0 1/40 (2.5%) 1
    Upper respiratory tract infection 0/38 (0%) 0 0/42 (0%) 0 1/41 (2.4%) 1 0/40 (0%) 0
    Injury, poisoning and procedural complications
    Overdose 0/38 (0%) 0 1/42 (2.4%) 1 0/41 (0%) 0 0/40 (0%) 0
    Procedural nausea 0/38 (0%) 0 1/42 (2.4%) 1 0/41 (0%) 0 0/40 (0%) 0
    Procedural vomiting 0/38 (0%) 0 1/42 (2.4%) 1 0/41 (0%) 0 0/40 (0%) 0
    Investigations
    Blood creatinine increased 1/38 (2.6%) 1 0/42 (0%) 0 0/41 (0%) 0 0/40 (0%) 0
    Metabolism and nutrition disorders
    Hyperkalaemia 0/38 (0%) 0 0/42 (0%) 0 0/41 (0%) 0 1/40 (2.5%) 1
    Musculoskeletal and connective tissue disorders
    Back pain 1/38 (2.6%) 1 0/42 (0%) 0 1/41 (2.4%) 1 1/40 (2.5%) 1
    Bone pain 0/38 (0%) 0 0/42 (0%) 0 0/41 (0%) 0 1/40 (2.5%) 2
    Nervous system disorders
    Syncope 0/38 (0%) 0 1/42 (2.4%) 1 0/41 (0%) 0 0/40 (0%) 0
    Renal and urinary disorders
    Acute kidney injury 0/38 (0%) 0 0/42 (0%) 0 0/41 (0%) 0 1/40 (2.5%) 1
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea 0/38 (0%) 0 1/42 (2.4%) 1 1/41 (2.4%) 2 0/40 (0%) 0
    Haemoptysis 0/38 (0%) 0 0/42 (0%) 0 1/41 (2.4%) 1 1/40 (2.5%) 1
    Pleural effusion 0/38 (0%) 0 0/42 (0%) 0 1/41 (2.4%) 1 0/40 (0%) 0
    Pneumothorax 1/38 (2.6%) 1 0/42 (0%) 0 0/41 (0%) 0 1/40 (2.5%) 1
    Pulmonary embolism 0/38 (0%) 0 1/42 (2.4%) 1 0/41 (0%) 0 1/40 (2.5%) 1
    Respiratory failure 0/38 (0%) 0 0/42 (0%) 0 1/41 (2.4%) 1 1/40 (2.5%) 1
    Surgical and medical procedures
    Thoracic cavity drainage 0/38 (0%) 0 0/42 (0%) 0 0/41 (0%) 0 1/40 (2.5%) 1
    Other (Not Including Serious) Adverse Events
    Ramucirumab Regimen 1 Ramucirumab Regimen 2 Ramucirumab Regimen 3 Ramucirumab Regimen 4
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 30/38 (78.9%) 31/42 (73.8%) 36/41 (87.8%) 31/40 (77.5%)
    Blood and lymphatic system disorders
    Anaemia 4/38 (10.5%) 12 5/42 (11.9%) 15 5/41 (12.2%) 11 1/40 (2.5%) 1
    Gastrointestinal disorders
    Abdominal distension 0/38 (0%) 0 1/42 (2.4%) 1 1/41 (2.4%) 1 3/40 (7.5%) 3
    Abdominal pain 6/38 (15.8%) 7 10/42 (23.8%) 14 7/41 (17.1%) 9 4/40 (10%) 8
    Constipation 2/38 (5.3%) 2 5/42 (11.9%) 8 7/41 (17.1%) 7 7/40 (17.5%) 7
    Diarrhoea 3/38 (7.9%) 4 9/42 (21.4%) 12 4/41 (9.8%) 5 5/40 (12.5%) 5
    Dyspepsia 0/38 (0%) 0 1/42 (2.4%) 1 0/41 (0%) 0 4/40 (10%) 4
    Dysphagia 1/38 (2.6%) 1 3/42 (7.1%) 9 2/41 (4.9%) 2 2/40 (5%) 2
    Nausea 6/38 (15.8%) 7 4/42 (9.5%) 4 4/41 (9.8%) 5 7/40 (17.5%) 9
    Vomiting 6/38 (15.8%) 8 6/42 (14.3%) 7 8/41 (19.5%) 13 7/40 (17.5%) 10
    General disorders
    Asthenia 2/38 (5.3%) 2 3/42 (7.1%) 3 4/41 (9.8%) 8 3/40 (7.5%) 4
    Early satiety 0/38 (0%) 0 3/42 (7.1%) 6 0/41 (0%) 0 1/40 (2.5%) 1
    Fatigue 10/38 (26.3%) 12 12/42 (28.6%) 17 6/41 (14.6%) 7 9/40 (22.5%) 9
    Oedema peripheral 1/38 (2.6%) 1 4/42 (9.5%) 5 2/41 (4.9%) 2 2/40 (5%) 3
    Pyrexia 4/38 (10.5%) 4 2/42 (4.8%) 2 4/41 (9.8%) 5 1/40 (2.5%) 1
    Infections and infestations
    Nasopharyngitis 2/38 (5.3%) 2 0/42 (0%) 0 0/41 (0%) 0 0/40 (0%) 0
    Injury, poisoning and procedural complications
    Infusion related reaction 2/38 (5.3%) 2 0/42 (0%) 0 2/41 (4.9%) 2 0/40 (0%) 0
    Investigations
    Alanine aminotransferase increased 3/38 (7.9%) 3 5/42 (11.9%) 7 0/41 (0%) 0 1/40 (2.5%) 1
    Aspartate aminotransferase increased 6/38 (15.8%) 6 5/42 (11.9%) 8 3/41 (7.3%) 3 1/40 (2.5%) 1
    Blood alkaline phosphatase increased 4/38 (10.5%) 4 5/42 (11.9%) 5 2/41 (4.9%) 2 1/40 (2.5%) 1
    Blood bilirubin increased 3/38 (7.9%) 3 0/42 (0%) 0 0/41 (0%) 0 0/40 (0%) 0
    Weight decreased 3/38 (7.9%) 4 2/42 (4.8%) 2 3/41 (7.3%) 3 2/40 (5%) 2
    Metabolism and nutrition disorders
    Decreased appetite 8/38 (21.1%) 11 9/42 (21.4%) 16 11/41 (26.8%) 13 7/40 (17.5%) 8
    Dehydration 2/38 (5.3%) 3 1/42 (2.4%) 4 1/41 (2.4%) 2 4/40 (10%) 6
    Hypoalbuminaemia 4/38 (10.5%) 5 2/42 (4.8%) 2 3/41 (7.3%) 4 0/40 (0%) 0
    Hyponatraemia 3/38 (7.9%) 3 1/42 (2.4%) 1 2/41 (4.9%) 3 1/40 (2.5%) 3
    Musculoskeletal and connective tissue disorders
    Back pain 2/38 (5.3%) 5 3/42 (7.1%) 5 1/41 (2.4%) 2 2/40 (5%) 2
    Muscular weakness 3/38 (7.9%) 4 1/42 (2.4%) 1 2/41 (4.9%) 3 0/40 (0%) 0
    Nervous system disorders
    Headache 4/38 (10.5%) 8 6/42 (14.3%) 8 5/41 (12.2%) 8 3/40 (7.5%) 3
    Lethargy 2/38 (5.3%) 2 1/42 (2.4%) 1 1/41 (2.4%) 1 0/40 (0%) 0
    Paraesthesia 2/38 (5.3%) 2 1/42 (2.4%) 1 0/41 (0%) 0 0/40 (0%) 0
    Psychiatric disorders
    Insomnia 1/38 (2.6%) 1 3/42 (7.1%) 3 2/41 (4.9%) 2 2/40 (5%) 2
    Renal and urinary disorders
    Proteinuria 4/38 (10.5%) 5 1/42 (2.4%) 1 2/41 (4.9%) 3 2/40 (5%) 2
    Respiratory, thoracic and mediastinal disorders
    Cough 2/38 (5.3%) 4 3/42 (7.1%) 6 1/41 (2.4%) 1 1/40 (2.5%) 1
    Dyspnoea 4/38 (10.5%) 5 3/42 (7.1%) 4 1/41 (2.4%) 1 4/40 (10%) 4
    Epistaxis 1/38 (2.6%) 1 2/42 (4.8%) 3 6/41 (14.6%) 7 2/40 (5%) 2
    Pleural effusion 2/38 (5.3%) 2 0/42 (0%) 0 1/41 (2.4%) 1 1/40 (2.5%) 1
    Skin and subcutaneous tissue disorders
    Pruritus 2/38 (5.3%) 3 1/42 (2.4%) 2 2/41 (4.9%) 2 1/40 (2.5%) 1
    Vascular disorders
    Hypertension 6/38 (15.8%) 8 2/42 (4.8%) 3 7/41 (17.1%) 8 6/40 (15%) 10

    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 less than or equal to 60 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:
    NCT02443883
    Other Study ID Numbers:
    • 15608
    • I4T-MC-JVDB
    • 2014-003791-23
    First Posted:
    May 14, 2015
    Last Update Posted:
    Jun 29, 2020
    Last Verified:
    Jul 1, 2019