Clincosm LogoSign in Get a demo

A Study of Ramucirumab (LY3009806) in Combination With Paclitaxel in Participants With Gastric Cancer

Sponsor
Eli Lilly and Company (Industry)
Overall Status
Completed
CT.gov ID
NCT02514551
Collaborator
(none)
245
Enrollment
52
Locations
2
Arms
38.5
Actual Duration (Months)
4.7
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 an alternative dose of ramucirumab in combination with paclitaxel in participants with second-line metastatic or locally advanced, unresectable gastric or gastroesophageal junction adenocarcinoma (GEJ).

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
245 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Randomized Phase 2 Trial Evaluating Alternative Ramucirumab Doses in Combination With Paclitaxel in Second-Line Metastatic or Locally Advanced, Unresectable Gastric or Gastroesophageal Junction Adenocarcinoma
Actual Study Start Date :
Oct 12, 2015
Actual Primary Completion Date :
Oct 27, 2017
Actual Study Completion Date :
Dec 28, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: 12mg/kg Ramucirumab + 80 mg/m² Paclitaxel

12 milligram per kilogram (mg/kg) ramucirumab administered intravenously (IV) on day 1 and day 15 (28 day cycles) in combination with 80 milligram per square meter (mg/m²) paclitaxel administered IV on day 1, day 8 and day 15.

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

    • Drug: Paclitaxel
    Administered IV
    Active Comparator: 8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel

    8 mg/kg ramucirumab administered IV on day 1 and day 15 (28 day cycles) in combination with 80 mg/m² paclitaxel administered IV on day 1, day 8 and day 15.

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

    • Drug: Paclitaxel
    Administered IV

    Outcome Measures

    Primary Outcome Measures

    1. Progression Free Survival (PFS) in Ramucirumab 12mg/kg Arm I4T-MC-JVCZ [Randomization to Objective Progressive Disease or Death (Up To 21 Months)]

      PFS was defined as time from the date of randomization(RD) to date of radiographic documentation of progression(RDP) or the date of death due to any cause, whichever is earlier as defined by RECIST v.1.1. Participants with no tumor progression and no death were censored at date of last adequate radiological assessment (AST) or date of RD(whichever is later).PD is at least a 20% increase in sum of diameters of target lesions,taking as reference the smallest sum on study.In addition to the relative increase of 20%,the sum must also demonstrate an absolute increase of at least 5 mm.The appearance of 1 or more new lesions is also considered progression.Non-Target PD is unequivocal progression of existing nontarget lesions.A participant with incomplete baseline disease had PFS time censored at the enrollment date.A participant not known to have died or have RDP as of the data inclusion cutoff date for the analysis had PFS time censored at date of the last complete RDP-free disease AST.

    Secondary Outcome Measures

    1. Progression Free Survival (PFS) Ramucirumab 12mg/kg Arm and 8mg/kg Arm in I4T-MC-JVCZ [Randomization to Objective Progressive Disease or Death (Up To 21 Months)]

      PFS was defined as time from the date of randomization(RD) to date of radiographic documentation of progression(RDP) or the date of death due to any cause, whichever is earlier as defined by RECIST v.1.1. Participants with no tumor progression and no death were censored at date of last adequate radiological assessment(AST) or date of RD(whichever is later).PD is at least a 20% increase in sum of diameters of target lesions,taking as reference the smallest sum on study.In addition to the relative increase of 20%,the sum must also demonstrate an absolute increase of at least 5 mm.The appearance of 1 or more new lesions is also considered progression.Non-Target PD is unequivocal progression of existing nontarget lesions.A participant with incomplete baseline disease had PFS time censored at the enrollment date.A participant not known to have died or have RDP as of the data inclusion cutoff date for the analysis had PFS time censored at date of the last complete RDP-free disease AST.

    2. Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab in Combination With Paclitaxel [Cycle(C) 1 Day(D) 1: Prior to Infusion(PTI),1 to 1.5 hours(hrs) after end of Infusion(EOI); C1 D15: 3 days PTI; C2 D1: 3 days PTI; C2 D15: 3 days PTI,1 to 1.5 hrs after EOI; C3 D1 and 15: 3 days PTI; C4 D1: 3 days PTI and 1 to 1.5 hrs after EOI]

      Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab in Combination with Paclitaxel

    3. Percentage of Participants Who Achieve Best Overall Tumor Response of Complete Response (CR) or Partial Response (PR) (Objective Response Rates [ORR]) [Baseline to Objective Progressive Disease (Up To 21 Months)]

      ORR was defined as the percentage of participants who achieved a PR or CR per RECIST v.1.1.CR is the disappearance of all target lesions.Any pathological lymph nodes(whether target or non-target)must have reduction in short axis to<10mm.Tumor marker results must have normalized.PR is at least a 30% decrease in the sum of diameter of target lesions,taking as reference the baseline sum diameters.ORR is calculated as a total number of participants with CR or PR divided by the total number of participants treated multiplied by 100.

    4. Percentage of Participants Who Exhibit Stable Disease (SD) or Confirmed Response (CR) or Partial Response (PR) [Disease Control Rate (DCR)] [Baseline to Objective Progressive Disease (Up To 21 Months)]

      DCR is defined as the percentage of participants who achieved CR, PR, or SD per RECIST v.1.1. CR is the disappearance of all target lesions. Any pathological lymph nodes (target or non-target) must have reduction in short axis to <10 mm.Tumor marker results must have normalized. PR is at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.The appearance of 1 or more new lesions is also considered progression. Non-Target PD is unequivocal progression of existing nontarget lesions. DCR=CR+PR+SD/total number of participants*100.

    5. Number of Participants With Anti-Ramucirumab Antibodies [Cycle 1 Predose through Follow-up (Up To 24 Months)]

      Participants who had anti-ramucirumab antibodies at postbaseline.

    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 diagnosis of gastric or GEJ adenocarcinoma.

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

    • The participant received combination chemotherapy, which must include a platinum and/or a fluoropyrimidine and must not include a taxane or antiangiogenic agent.

    • The disease is evaluable by imaging per Response Evaluation Criteria in Solid Tumors 1.1.

    • The participant has an Eastern Cooperative Oncology Group performance status of 0 or

    • The participant has adequate organ function:

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

    • Serum creatinine ≤1.5 × ULN or calculated creatinine clearance ≥50 milliliters/minute.

    • Urinary protein is <2+.

    • Absolute neutrophil count ≥1.5 × 109/liter (L), platelets ≥100 × 109/L, and hemoglobin ≥9 grams/deciliter (5.58 millimoles/L).

    • International normalized ratio ≤1.5 × ULN and partial thromboplastin time ≤5 seconds above ULN.

    • The participant has an estimated life expectancy of minimum 12 weeks.

    • The participant has resolution to Grade 1 or less by Common Terminology Criteria for Adverse Events Version 4.0, of all clinically significant toxic effects of previous therapy.

    • The participant, if male, is sterile or agrees to use a reliable method of birth control.

    • The participant, if female, is surgically sterile, is postmenopausal, or agrees to use a highly effective method of birth control.

    • The participant, if female and of child-bearing potential, must have a negative pregnancy test.

    Exclusion Criteria:

    • The participant is receiving therapy with any of the following:

    • Nonsteroidal anti-inflammatory agents.

    • Other anti-platelet agents; 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 previous chemotherapy with a cumulative dose of >900 mg per meter squared (mg/m2) of epirubicin or >400 mg/m2 of doxorubicin.

    • The participant has documented brain metastases or leptomeningeal disease.

    • The participant has a significant bleeding disorder or vasculitis.

    • The participant experienced any arterial thromboembolic event within 6 months.

    • The participant has symptomatic congestive heart failure or symptomatic cardiac arrhythmia.

    • The participant has uncontrolled hypertension, despite antihypertensive intervention.

    • The participant underwent major surgery within 28 days.

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

    • The participant has a history of inflammatory bowel disease or Crohn's disease requiring medical intervention within 12 months.

    • The participant has bowel obstruction or history of chronic diarrhea that is considered clinically significant.

    • The participant has either of the following:

    • Child-pugh B or C cirrhosis.

    • The participant has a serious illness or medical condition including:

    • Human immunodeficiency virus infection.

    • The participant has a concurrent active malignancy other than the following:

    • Nonmelanomatous skin cancer.

    • In situ carcinoma of the cervix or other noninvasive carcinoma or in situ neoplasm.

    • The participant has a serious nonhealing: (a) wound, (b) peptic ulcer, or (c) bone fracture.

    • The participant experienced any Grade 3 or 4 venous thromboembolic event that is not adequately treated.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 City of Hope National Medical Center Duarte California United States 91010-0269
    2 University of Kansas Medical Center Westwood Kansas United States 66205
    3 Dana Farber Cancer Institute Boston Massachusetts United States 02215
    4 Montefiore Medical Center Bronx New York United States 10461
    5 Weill Cornell Medical College New York New York United States 10021
    6 Scott & White Memorial Hospital & Clinic Temple Texas United States 76508
    7 Vista Oncology Inc. PS Olympia Washington United States 98502
    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. Brussels Belgium 1000
    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. Kortrijk Belgium 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. Namur Belgium 5000
    11 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. Calgary Canada T2N 4N2
    12 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. Oshawa Canada L1G 2B9
    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. Brno Czechia 656 53
    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. Novy Jicin Czechia 741 01
    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. Praha Czechia 140 59
    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. Praha Czechia 150 06
    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. Berlin Germany 13353
    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. Frankfurt am Main Germany 60488
    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. Hamburg Germany 20246
    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. Ravensburg Germany 88212
    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. Athens Greece 18537
    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. Haidari Greece 12462
    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. Heraklion Greece 71110
    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. N. Efkarpia Greece 56403
    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. Patras Greece 26504
    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. Cagliari Italy 09042
    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. Cremona Italy 26100
    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. Faenza Italy 48018
    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. Milano Italy 20089
    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. Reggio Emilia Italy 42100
    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. San Giovanni Rotondo Italy 71013
    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. Barcelona Spain 08208
    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. Barcelona Spain 17007
    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. Girona Spain 17007
    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. Madrid Spain 28041
    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. Madrid Spain 28050
    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. Malaga Spain 29010
    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. Santander Spain 39008
    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. Sevilla Spain 41013
    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. Valencia Spain 46014
    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. Goteborg Sweden 413 56
    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. Linkoping Sweden 58185
    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. Ankara Turkey 06100
    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. Edirne Turkey 22770
    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. Istanbul Turkey 34098
    46 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. Kayseri Turkey 38039
    47 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. Malatya Turkey 44280
    48 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. Dnipropetrovsk Ukraine 49102
    49 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. Kyiv Ukraine 04107
    50 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. Lutsk Ukraine 63000
    51 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. Sumy Ukraine 40005
    52 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. Vinnitsa Ukraine 21029

    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)

    More Information

    Publications

    None provided.
    Responsible Party:
    Eli Lilly and Company
    ClinicalTrials.gov Identifier:
    NCT02514551
    Other Study ID Numbers:
    • 15541
    • I4T-MC-JVCZ
    • 2014-005067-32
    First Posted:
    Aug 3, 2015
    Last Update Posted:
    Jun 17, 2020
    Last Verified:
    Jun 1, 2020
    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
    Paclitaxel
    Ramucirumab

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail Completers are defined as participants who died or had progressive disease (PD) or completed treatment or did not complete treatment and were followed for survival data. Final study data will be provided after study completion.
    Arm/Group Title 12mg/kg Ramucirumab + 80 mg/m² Paclitaxel 8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel
    Arm/Group Description 12 milligram per kilogram (mg/kg) ramucirumab administered intravenously (IV) on day 1 and day 15 (28 day cycles) in combination with 80 milligram per square meter (mg/m²) paclitaxel administered IV on day 1, day 8 and day 15. 8 mg/kg ramucirumab administered IV on day 1 and day 15 (28 day cycles) in combination with 80 mg/m² paclitaxel administered IV on day 1, day 8 and day 15.
    Period Title: Overall Study
    STARTED 123 122
    Received at Least One Dose of Study Drug 123 120
    COMPLETED 123 119
    NOT COMPLETED 0 3

    Baseline Characteristics

    Arm/Group Title 12mg/kg Ramucirumab + 80 mg/m² Paclitaxel 8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel Total
    Arm/Group Description 12mg/kg ramucirumab administered intravenously (IV) on day 1 and day 15 (28 day cycles) in combination with 80 mg/m² paclitaxel administered IV on day 1, day 8 and day 15. 8 mg/kg ramucirumab administered IV on day 1 and day 15 (28 day cycles) in combination with 80 mg/m² paclitaxel administered IV on day 1, day 8 and day 15. Total of all reporting groups
    Overall Participants 123 122 245
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    58.6
    (11.4)
    57.9
    (12.3)
    58.3
    (11.8)
    Sex: Female, Male (Count of Participants)
    Female
    40
    32.5%
    44
    36.1%
    84
    34.3%
    Male
    83
    67.5%
    78
    63.9%
    161
    65.7%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    8
    6.5%
    7
    5.7%
    15
    6.1%
    Not Hispanic or Latino
    110
    89.4%
    108
    88.5%
    218
    89%
    Unknown or Not Reported
    5
    4.1%
    7
    5.7%
    12
    4.9%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    1
    0.8%
    0
    0%
    1
    0.4%
    Asian
    0
    0%
    3
    2.5%
    3
    1.2%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    2
    1.6%
    2
    1.6%
    4
    1.6%
    White
    119
    96.7%
    117
    95.9%
    236
    96.3%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    1
    0.8%
    0
    0%
    1
    0.4%
    Region of Enrollment (Count of Participants)
    Greece
    10
    8.1%
    11
    9%
    21
    8.6%
    Canada
    0
    0%
    4
    3.3%
    4
    1.6%
    Sweden
    1
    0.8%
    1
    0.8%
    2
    0.8%
    Turkey
    24
    19.5%
    16
    13.1%
    40
    16.3%
    Belgium
    6
    4.9%
    5
    4.1%
    11
    4.5%
    United States
    16
    13%
    8
    6.6%
    24
    9.8%
    Czechia
    7
    5.7%
    9
    7.4%
    16
    6.5%
    Ukraine
    18
    14.6%
    26
    21.3%
    44
    18%
    Italy
    16
    13%
    7
    5.7%
    23
    9.4%
    Germany
    2
    1.6%
    2
    1.6%
    4
    1.6%
    Spain
    23
    18.7%
    33
    27%
    56
    22.9%

    Outcome Measures

    1. Primary Outcome
    Title Progression Free Survival (PFS) in Ramucirumab 12mg/kg Arm I4T-MC-JVCZ
    Description PFS was defined as time from the date of randomization(RD) to date of radiographic documentation of progression(RDP) or the date of death due to any cause, whichever is earlier as defined by RECIST v.1.1. Participants with no tumor progression and no death were censored at date of last adequate radiological assessment (AST) or date of RD(whichever is later).PD is at least a 20% increase in sum of diameters of target lesions,taking as reference the smallest sum on study.In addition to the relative increase of 20%,the sum must also demonstrate an absolute increase of at least 5 mm.The appearance of 1 or more new lesions is also considered progression.Non-Target PD is unequivocal progression of existing nontarget lesions.A participant with incomplete baseline disease had PFS time censored at the enrollment date.A participant not known to have died or have RDP as of the data inclusion cutoff date for the analysis had PFS time censored at date of the last complete RDP-free disease AST.
    Time Frame Randomization to Objective Progressive Disease or Death (Up To 21 Months)

    Outcome Measure Data

    Analysis Population Description
    All randomized participants in arm 12mg/kg Ramucirumab + 80 mg/m² Paclitaxel. Number of participants censored: Ramucirumab 12 mg/kg + 80 mg/m² Paclitaxel= 25. All randomized participants (including the censored participants) were included in the analyses.
    Arm/Group Title I4T-MC-JVCZ: 12mg/kg Ramucirumab + 80 mg/m² Paclitaxel
    Arm/Group Description 12mg/kg ramucirumab administered intravenously (IV) on day 1 and day 15 (28 day cycles) in combination with 80 mg/m² paclitaxel administered IV on day 1, day 8 and day 15.
    Measure Participants 123
    Median (95% Confidence Interval) [months]
    5.42
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection I4T-MC-JVCZ: 12mg/kg Ramucirumab + 80 mg/m² Paclitaxel
    Comments This analysis were comparison of PFS for participants treated with ramucirumab 12 mg/kg plus paclitaxel in Study I4T-MC-JVCZ versus placebo plus paclitaxel in I4T-IE-JVBE (NCT01170663) using meta-analysis. Placebo + 80 mg/m² Paclitaxel in I4T-IE-JVBE Number of participants: 335, Median (95% CI), months: 2.86 (2.79 to 3.02)
    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 0.617
    Confidence Interval (2-Sided) 95%
    0.447 to 0.853
    Parameter Dispersion Type:
    Value:
    Estimation Comments Unstratified cox proportional hazards model comparing Ramucirumab I4T-MC-JVCZ and I4T-IE-JVBE (NCT01170663)
    2. Secondary Outcome
    Title Progression Free Survival (PFS) Ramucirumab 12mg/kg Arm and 8mg/kg Arm in I4T-MC-JVCZ
    Description PFS was defined as time from the date of randomization(RD) to date of radiographic documentation of progression(RDP) or the date of death due to any cause, whichever is earlier as defined by RECIST v.1.1. Participants with no tumor progression and no death were censored at date of last adequate radiological assessment(AST) or date of RD(whichever is later).PD is at least a 20% increase in sum of diameters of target lesions,taking as reference the smallest sum on study.In addition to the relative increase of 20%,the sum must also demonstrate an absolute increase of at least 5 mm.The appearance of 1 or more new lesions is also considered progression.Non-Target PD is unequivocal progression of existing nontarget lesions.A participant with incomplete baseline disease had PFS time censored at the enrollment date.A participant not known to have died or have RDP as of the data inclusion cutoff date for the analysis had PFS time censored at date of the last complete RDP-free disease AST.
    Time Frame Randomization to Objective Progressive Disease or Death (Up To 21 Months)

    Outcome Measure Data

    Analysis Population Description
    All randomized participants. Number of participants censored: Ramucirumab 12 mg/kg + Paclitaxel 80 mg/m2= 25 and 8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel =23. All randomized participants (including the censored participants) were included in the analyses.
    Arm/Group Title 12mg/kg Ramucirumab + 80 mg/m² Paclitaxel 8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel
    Arm/Group Description 12mg/kg ramucirumab administered intravenously (IV) on day 1 and day 15 (28 day cycles) in combination with 80 mg/m² paclitaxel administered IV on day 1, day 8 and day 15. 8 mg/kg ramucirumab administered IV on day 1 and day 15 (28 day cycles) in combination with 80 mg/m² paclitaxel administered IV on day 1, day 8 and day 15.
    Measure Participants 123 122
    Median (95% Confidence Interval) [months]
    5.42
    5.16
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection I4T-MC-JVCZ: 12mg/kg Ramucirumab + 80 mg/m² Paclitaxel, 8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel
    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 0.963
    Confidence Interval (2-Sided) 95%
    0.727 to 1.274
    Parameter Dispersion Type:
    Value:
    Estimation Comments Unstratified cox proportional hazards model.
    3. Secondary Outcome
    Title Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab in Combination With Paclitaxel
    Description Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab in Combination with Paclitaxel
    Time Frame Cycle(C) 1 Day(D) 1: Prior to Infusion(PTI),1 to 1.5 hours(hrs) after end of Infusion(EOI); C1 D15: 3 days PTI; C2 D1: 3 days PTI; C2 D15: 3 days PTI,1 to 1.5 hrs after EOI; C3 D1 and 15: 3 days PTI; C4 D1: 3 days PTI and 1 to 1.5 hrs after EOI

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least one dose of study drug and had evaluable PK data.
    Arm/Group Title 12mg/kg Ramucirumab + 80 mg/m² Paclitaxel 8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel
    Arm/Group Description 12mg/kg ramucirumab administered intravenously (IV) on day 1 and day 15 (28 day cycles) in combination with 80 mg/m² paclitaxel administered IV on day 1, day 8 and day 15. 8 mg/kg ramucirumab administered IV on day 1 and day 15 (28 day cycles) in combination with 80 mg/m² paclitaxel administered IV on day 1, day 8 and day 15.
    Measure Participants 103 95
    Cycle 1 Day 15 (Week 2)
    39.2
    (43)
    21.4
    (58)
    Cycle 2 Day 1 (Week 4)
    63.6
    (40)
    37.1
    (50)
    Cycle 2 Day 15 (Week 6)
    76.7
    (42)
    43.5
    (53)
    Cycle 3 Day 1(Week 8)
    91.2
    (40)
    51.5
    (55)
    Cycle 3 Day 15 (Week 10)
    99.0
    (44)
    52.9
    (56)
    Cycle 4 Day 1 (Week 12)
    101
    (55)
    56.1
    (56)
    4. Secondary Outcome
    Title Percentage of Participants Who Achieve Best Overall Tumor Response of Complete Response (CR) or Partial Response (PR) (Objective Response Rates [ORR])
    Description ORR was defined as the percentage of participants who achieved a PR or CR per RECIST v.1.1.CR is the disappearance of all target lesions.Any pathological lymph nodes(whether target or non-target)must have reduction in short axis to<10mm.Tumor marker results must have normalized.PR is at least a 30% decrease in the sum of diameter of target lesions,taking as reference the baseline sum diameters.ORR is calculated as a total number of participants with CR or PR divided by the total number of participants treated multiplied by 100.
    Time Frame Baseline to Objective Progressive Disease (Up To 21 Months)

    Outcome Measure Data

    Analysis Population Description
    All randomized participants.
    Arm/Group Title 12mg/kg Ramucirumab + 80 mg/m² Paclitaxel 8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel
    Arm/Group Description 12mg/kg ramucirumab administered intravenously (IV) on day 1 and day 15 (28 day cycles) in combination with 80 mg/m² paclitaxel administered IV on day 1, day 8 and day 15. 8 mg/kg ramucirumab administered IV on day 1 and day 15 (28 day cycles) in combination with 80 mg/m² paclitaxel administered IV on day 1, day 8 and day 15.
    Measure Participants 123 122
    Number [percentage of participants]
    27.6
    22.4%
    25.4
    20.8%
    5. Secondary Outcome
    Title Percentage of Participants Who Exhibit Stable Disease (SD) or Confirmed Response (CR) or Partial Response (PR) [Disease Control Rate (DCR)]
    Description DCR is defined as the percentage of participants who achieved CR, PR, or SD per RECIST v.1.1. CR is the disappearance of all target lesions. Any pathological lymph nodes (target or non-target) must have reduction in short axis to <10 mm.Tumor marker results must have normalized. PR is at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.The appearance of 1 or more new lesions is also considered progression. Non-Target PD is unequivocal progression of existing nontarget lesions. DCR=CR+PR+SD/total number of participants*100.
    Time Frame Baseline to Objective Progressive Disease (Up To 21 Months)

    Outcome Measure Data

    Analysis Population Description
    All randomized participants.
    Arm/Group Title 12mg/kg Ramucirumab + 80 mg/m² Paclitaxel 8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel
    Arm/Group Description 12mg/kg ramucirumab administered intravenously (IV) on day 1 and day 15 (28 day cycles) in combination with 80 mg/m² paclitaxel administered IV on day 1, day 8 and day 15. 8 mg/kg ramucirumab administered IV on day 1 and day 15 (28 day cycles) in combination with 80 mg/m² paclitaxel administered IV on day 1, day 8 and day 15.
    Measure Participants 123 122
    Number [percentage of participants]
    78.9
    64.1%
    75.4
    61.8%
    6. Secondary Outcome
    Title Number of Participants With Anti-Ramucirumab Antibodies
    Description Participants who had anti-ramucirumab antibodies at postbaseline.
    Time Frame Cycle 1 Predose through Follow-up (Up To 24 Months)

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least one dose of study drug and were evaluable for ramucirumab anti-drug antibody.
    Arm/Group Title 12mg/kg Ramucirumab + 80 mg/m² Paclitaxel 8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel
    Arm/Group Description 12mg/kg ramucirumab administered intravenously (IV) on day 1 and day 15 (28 day cycles) in combination with 80 mg/m² paclitaxel administered IV on day 1, day 8 and day 15. 8 mg/kg ramucirumab administered IV on day 1 and day 15 (28 day cycles) in combination with 80 mg/m² paclitaxel administered IV on day 1, day 8 and day 15.
    Measure Participants 105 89
    Count of Participants [Participants]
    2
    1.6%
    1
    0.8%

    Adverse Events

    Time Frame Up To 40 Months
    Adverse Event Reporting Description All randomized participants who received at least one dose of study drug.
    Arm/Group Title 12mg/kg Ramucirumab + 80 mg/m² Paclitaxel 8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel
    Arm/Group Description 12mg/kg ramucirumab administered intravenously (IV) on day 1 and day 15 (28 day cycles) in combination with 80 mg/m² paclitaxel administered IV on day 1, day 8 and day 15. 8 mg/kg ramucirumab administered IV on day 1 and day 15 (28 day cycles) in combination with 80 mg/m² paclitaxel administered IV on day 1, day 8 and day 15.
    All Cause Mortality
    12mg/kg Ramucirumab + 80 mg/m² Paclitaxel 8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 81/123 (65.9%) 76/120 (63.3%)
    Serious Adverse Events
    12mg/kg Ramucirumab + 80 mg/m² Paclitaxel 8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 47/123 (38.2%) 32/120 (26.7%)
    Blood and lymphatic system disorders
    Anaemia 3/123 (2.4%) 3 3/120 (2.5%) 3
    Bone marrow failure 0/123 (0%) 0 1/120 (0.8%) 2
    Febrile neutropenia 4/123 (3.3%) 4 3/120 (2.5%) 3
    Leukocytosis 1/123 (0.8%) 1 0/120 (0%) 0
    Neutropenia 0/123 (0%) 0 1/120 (0.8%) 2
    Cardiac disorders
    Cardiac failure 1/123 (0.8%) 1 0/120 (0%) 0
    Cardiopulmonary failure 0/123 (0%) 0 1/120 (0.8%) 1
    Cardiovascular insufficiency 0/123 (0%) 0 1/120 (0.8%) 1
    Gastrointestinal disorders
    Abdominal pain 4/123 (3.3%) 5 2/120 (1.7%) 2
    Ascites 1/123 (0.8%) 1 1/120 (0.8%) 1
    Diarrhoea 1/123 (0.8%) 1 1/120 (0.8%) 1
    Dysphagia 1/123 (0.8%) 1 0/120 (0%) 0
    Gastric haemorrhage 3/123 (2.4%) 6 1/120 (0.8%) 1
    Gastric perforation 0/123 (0%) 0 1/120 (0.8%) 1
    Gastric stenosis 1/123 (0.8%) 1 0/120 (0%) 0
    Gastrointestinal haemorrhage 2/123 (1.6%) 2 0/120 (0%) 0
    Haematemesis 1/123 (0.8%) 1 0/120 (0%) 0
    Ileus 0/123 (0%) 0 2/120 (1.7%) 2
    Large intestinal haemorrhage 1/123 (0.8%) 1 0/120 (0%) 0
    Nausea 1/123 (0.8%) 1 0/120 (0%) 0
    Oesophageal fistula 1/123 (0.8%) 1 0/120 (0%) 0
    Oesophageal haemorrhage 0/123 (0%) 0 1/120 (0.8%) 1
    Oesophageal obstruction 1/123 (0.8%) 1 0/120 (0%) 0
    Oesophageal perforation 0/123 (0%) 0 1/120 (0.8%) 1
    Pneumoperitoneum 0/123 (0%) 0 1/120 (0.8%) 1
    Small intestinal obstruction 1/123 (0.8%) 1 1/120 (0.8%) 1
    Tongue oedema 1/123 (0.8%) 1 0/120 (0%) 0
    Upper gastrointestinal haemorrhage 1/123 (0.8%) 1 1/120 (0.8%) 1
    Vomiting 3/123 (2.4%) 3 1/120 (0.8%) 1
    General disorders
    Asthenia 2/123 (1.6%) 2 0/120 (0%) 0
    Death 1/123 (0.8%) 1 0/120 (0%) 0
    Fatigue 1/123 (0.8%) 1 1/120 (0.8%) 1
    General physical health deterioration 2/123 (1.6%) 2 0/120 (0%) 0
    Localised oedema 1/123 (0.8%) 1 0/120 (0%) 0
    Malaise 0/123 (0%) 0 1/120 (0.8%) 1
    Oedema 1/123 (0.8%) 1 0/120 (0%) 0
    Organ failure 1/123 (0.8%) 1 0/120 (0%) 0
    Pyrexia 1/123 (0.8%) 1 0/120 (0%) 0
    Hepatobiliary disorders
    Cholangitis 0/123 (0%) 0 1/120 (0.8%) 1
    Cholecystitis 0/123 (0%) 0 1/120 (0.8%) 1
    Cholecystitis acute 1/123 (0.8%) 1 0/120 (0%) 0
    Cholelithiasis 1/123 (0.8%) 1 0/120 (0%) 0
    Gallbladder rupture 1/123 (0.8%) 1 0/120 (0%) 0
    Hepatitis toxic 1/123 (0.8%) 1 0/120 (0%) 0
    Jaundice 2/123 (1.6%) 3 0/120 (0%) 0
    Infections and infestations
    Bacteraemia 0/123 (0%) 0 1/120 (0.8%) 1
    Bronchitis 0/123 (0%) 0 1/120 (0.8%) 1
    Clostridium difficile colitis 1/123 (0.8%) 1 0/120 (0%) 0
    Device related infection 0/123 (0%) 0 1/120 (0.8%) 1
    Enteritis infectious 1/123 (0.8%) 1 0/120 (0%) 0
    Escherichia infection 0/123 (0%) 0 1/120 (0.8%) 1
    Infection 2/123 (1.6%) 2 0/120 (0%) 0
    Lung infection 1/123 (0.8%) 1 1/120 (0.8%) 1
    Peritonitis 0/123 (0%) 0 1/120 (0.8%) 1
    Pneumonia 0/123 (0%) 0 1/120 (0.8%) 2
    Pneumonia necrotising 0/123 (0%) 0 1/120 (0.8%) 1
    Respiratory tract infection 1/123 (0.8%) 1 0/120 (0%) 0
    Sepsis 1/123 (0.8%) 1 0/120 (0%) 0
    Septic shock 1/123 (0.8%) 1 0/120 (0%) 0
    Injury, poisoning and procedural complications
    Femoral neck fracture 0/123 (0%) 0 1/120 (0.8%) 1
    Infusion related reaction 1/123 (0.8%) 1 0/120 (0%) 0
    Tibia fracture 1/123 (0.8%) 1 0/120 (0%) 0
    Investigations
    Aspartate aminotransferase increased 1/123 (0.8%) 1 0/120 (0%) 0
    Blood bilirubin increased 2/123 (1.6%) 2 0/120 (0%) 0
    Neutrophil count decreased 6/123 (4.9%) 6 0/120 (0%) 0
    Metabolism and nutrition disorders
    Cachexia 1/123 (0.8%) 1 0/120 (0%) 0
    Decreased appetite 0/123 (0%) 0 1/120 (0.8%) 1
    Dehydration 0/123 (0%) 0 1/120 (0.8%) 1
    Hyperkalaemia 1/123 (0.8%) 1 0/120 (0%) 0
    Hypokalaemia 1/123 (0.8%) 1 0/120 (0%) 0
    Hyponatraemia 1/123 (0.8%) 1 0/120 (0%) 0
    Malnutrition 1/123 (0.8%) 1 0/120 (0%) 0
    Musculoskeletal and connective tissue disorders
    Back pain 1/123 (0.8%) 1 1/120 (0.8%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Lymphangiosis carcinomatosa 0/123 (0%) 0 1/120 (0.8%) 1
    Tumour haemorrhage 0/123 (0%) 0 1/120 (0.8%) 1
    Tumour perforation 1/123 (0.8%) 1 0/120 (0%) 0
    Nervous system disorders
    Syncope 0/123 (0%) 0 1/120 (0.8%) 1
    Renal and urinary disorders
    Acute kidney injury 1/123 (0.8%) 2 0/120 (0%) 0
    Proteinuria 0/123 (0%) 0 1/120 (0.8%) 1
    Renal failure 1/123 (0.8%) 1 0/120 (0%) 0
    Reproductive system and breast disorders
    Oedema genital 1/123 (0.8%) 1 0/120 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Aspiration 0/123 (0%) 0 1/120 (0.8%) 1
    Dyspnoea 1/123 (0.8%) 2 1/120 (0.8%) 1
    Hiccups 1/123 (0.8%) 1 0/120 (0%) 0
    Hypoxia 0/123 (0%) 0 1/120 (0.8%) 1
    Pneumonitis 0/123 (0%) 0 1/120 (0.8%) 1
    Pneumothorax 1/123 (0.8%) 1 0/120 (0%) 0
    Pulmonary embolism 0/123 (0%) 0 1/120 (0.8%) 1
    Pulmonary hypertension 0/123 (0%) 0 1/120 (0.8%) 1
    Respiratory distress 0/123 (0%) 0 1/120 (0.8%) 1
    Vascular disorders
    Hypotension 0/123 (0%) 0 1/120 (0.8%) 1
    Shock haemorrhagic 1/123 (0.8%) 1 0/120 (0%) 0
    Other (Not Including Serious) Adverse Events
    12mg/kg Ramucirumab + 80 mg/m² Paclitaxel 8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 117/123 (95.1%) 115/120 (95.8%)
    Blood and lymphatic system disorders
    Anaemia 34/123 (27.6%) 72 39/120 (32.5%) 77
    Leukopenia 9/123 (7.3%) 44 9/120 (7.5%) 18
    Neutropenia 22/123 (17.9%) 78 24/120 (20%) 62
    Thrombocytopenia 7/123 (5.7%) 10 4/120 (3.3%) 5
    Gastrointestinal disorders
    Abdominal distension 7/123 (5.7%) 9 6/120 (5%) 8
    Abdominal pain 20/123 (16.3%) 31 19/120 (15.8%) 22
    Abdominal pain upper 8/123 (6.5%) 13 12/120 (10%) 16
    Ascites 9/123 (7.3%) 11 5/120 (4.2%) 8
    Constipation 23/123 (18.7%) 33 21/120 (17.5%) 27
    Diarrhoea 31/123 (25.2%) 78 35/120 (29.2%) 65
    Dysphagia 11/123 (8.9%) 12 4/120 (3.3%) 4
    Nausea 27/123 (22%) 52 38/120 (31.7%) 95
    Stomatitis 15/123 (12.2%) 19 18/120 (15%) 41
    Vomiting 29/123 (23.6%) 51 27/120 (22.5%) 44
    General disorders
    Asthenia 15/123 (12.2%) 35 19/120 (15.8%) 49
    Fatigue 43/123 (35%) 85 46/120 (38.3%) 82
    Oedema peripheral 10/123 (8.1%) 11 16/120 (13.3%) 22
    Pyrexia 9/123 (7.3%) 10 8/120 (6.7%) 8
    Investigations
    Alanine aminotransferase increased 14/123 (11.4%) 27 7/120 (5.8%) 8
    Aspartate aminotransferase increased 20/123 (16.3%) 43 8/120 (6.7%) 15
    Blood alkaline phosphatase increased 9/123 (7.3%) 25 10/120 (8.3%) 14
    Blood bilirubin increased 8/123 (6.5%) 12 2/120 (1.7%) 3
    Neutrophil count decreased 30/123 (24.4%) 91 24/120 (20%) 60
    Platelet count decreased 9/123 (7.3%) 15 7/120 (5.8%) 13
    Weight decreased 14/123 (11.4%) 16 13/120 (10.8%) 17
    White blood cell count decreased 13/123 (10.6%) 33 14/120 (11.7%) 35
    Metabolism and nutrition disorders
    Decreased appetite 25/123 (20.3%) 41 32/120 (26.7%) 58
    Hyperglycaemia 8/123 (6.5%) 18 11/120 (9.2%) 20
    Hypoalbuminaemia 10/123 (8.1%) 13 14/120 (11.7%) 34
    Hyponatraemia 7/123 (5.7%) 13 7/120 (5.8%) 8
    Musculoskeletal and connective tissue disorders
    Arthralgia 8/123 (6.5%) 13 5/120 (4.2%) 5
    Back pain 10/123 (8.1%) 13 9/120 (7.5%) 14
    Myalgia 11/123 (8.9%) 18 9/120 (7.5%) 16
    Nervous system disorders
    Dysgeusia 5/123 (4.1%) 5 9/120 (7.5%) 13
    Headache 10/123 (8.1%) 12 9/120 (7.5%) 12
    Neuropathy peripheral 15/123 (12.2%) 38 15/120 (12.5%) 22
    Paraesthesia 13/123 (10.6%) 30 13/120 (10.8%) 29
    Peripheral sensory neuropathy 8/123 (6.5%) 15 20/120 (16.7%) 46
    Renal and urinary disorders
    Proteinuria 9/123 (7.3%) 19 8/120 (6.7%) 11
    Respiratory, thoracic and mediastinal disorders
    Cough 14/123 (11.4%) 17 8/120 (6.7%) 11
    Dysphonia 11/123 (8.9%) 15 6/120 (5%) 7
    Dyspnoea 4/123 (3.3%) 5 12/120 (10%) 13
    Epistaxis 26/123 (21.1%) 43 28/120 (23.3%) 36
    Skin and subcutaneous tissue disorders
    Alopecia 19/123 (15.4%) 19 24/120 (20%) 28
    Vascular disorders
    Hypertension 24/123 (19.5%) 44 21/120 (17.5%) 46

    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:
    NCT02514551
    Other Study ID Numbers:
    • 15541
    • I4T-MC-JVCZ
    • 2014-005067-32
    First Posted:
    Aug 3, 2015
    Last Update Posted:
    Jun 17, 2020
    Last Verified:
    Jun 1, 2020