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A Study of Ramucirumab in Participants With Gastric, Esophageal, and Gastroesophageal Cancer

Sponsor
Eli Lilly and Company (Industry)
Overall Status
Completed
CT.gov ID
NCT01246960
Collaborator
(none)
168
Enrollment
58
Locations
2
Arms
37
Duration (Months)
2.9
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether ramucirumab when used in conjunction with chemotherapy treatment can help participants with stomach, esophagus, and gastroesophageal cancer.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
168 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
Randomized, Placebo-Controlled, Double-Blind Phase 2 Study of mFOLFOX6 Chemotherapy Plus Ramucirumab Drug Product(IMC-1121B) Versus mFOLFOX6 Plus Placebo for Advanced Adenocarcinoma of the Esophagus, Gastroesophageal Junction or Stomach
Study Start Date :
Apr 1, 2011
Actual Primary Completion Date :
Sep 1, 2013
Actual Study Completion Date :
May 1, 2014

Arms and Interventions

Arm Intervention/Treatment
Experimental: Ramucirumab

Oxaliplatin 85 milligrams per square meter (mg/m^2) given on Day 1 of a 2-week cycle Leucovorin 400 mg/m^2 given on Day 1 of a 2-week cycle 5-Fluorouracil (5-FU) 400 mg/m^2 bolus given on Day 1 of a 2-week cycle 5-FU 2400 mg/m^2 continuously given over 46-48 hours on Day 1 of a 2-week cycle Ramucirumab 8 milligrams per kilogram (mg/kg) given on Day 1 of a 2-week cycle Participants will receive study treatment every 2 weeks until disease progression, unacceptable toxicity, or another withdrawal criterion is met

Biological: Ramucirumab
Administered intravenously
Other Names:
  • LY3009806
  • IMC-1121B

    • Drug: Oxaliplatin
    Administered intravenously

    Drug: Leucovorin
    Administered intravenously

    Drug: 5-Fluorouracil
    Administered intravenously
    Other Names:
  • 5-FU

    		•
    Placebo Comparator: Placebo

    Oxaliplatin 85 mg/m^2 given on Day 1 of a 2-week cycle Leucovorin 400 mg/m^2 given on Day 1 of a 2-week cycle 5-FU 400 mg/m^2 bolus given on Day 1 of a 2-week cycle 5-FU 2400 mg/m^2 continuously given over 46-48 hours on Day 1 of a 2-week cycle Placebo given on Day 1 of a 2-week cycle Participants will receive study treatment every 2 weeks until disease progression, unacceptable toxicity, or another withdrawal criterion is met

    Drug: Placebo
    Administered intravenously

    Drug: Oxaliplatin
    Administered intravenously

    Drug: Leucovorin
    Administered intravenously

    Drug: 5-Fluorouracil
    Administered intravenously
    Other Names:
  • 5-FU

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Progression-Free Survival (PFS) [Randomization to measured PD or date of death from any cause (up to Month 25.0)]

      PFS was defined using Response Evaluation Criteria in Solid Tumors [RECIST version (v.) 1.1] as the time from randomization to the first observation of progressive disease (PD) or death due to any cause, whichever came first. PD was a ≥20% increase in the sum of the diameters of target lesions with the sum demonstrating an absolute increase of ≥5 millimeters (mm); the appearance of ≥1 new lesions or unequivocal progression of non-target lesions. If a participant did not have a baseline disease assessment, PFS time was censored at the randomization date, regardless of whether or not PD or death was observed. Participants not known to have died or have objective PD were censored at the last post-baseline radiological assessment date.

    Secondary Outcome Measures

    1. Overall Survival (OS) [Randomization to date of death from any cause (up to Month 28.3)]

      OS was defined as the time from randomization to death due to any cause. OS was censored at the date of the last follow-up visit for participants who were alive or lost to follow-up.

    2. Percentage of Participants Achieving an Objective Response (Objective Response Rate) [Randomization to measured PD (up to Month 23.0)]

      The percentage of participants who achieved a best overall response of partial response (PR) or complete response (CR) is reported. Response was defined using RECIST, v. 1.1 criteria. CR was the disappearance of all lesions and pathological lymph node reduction in the short axis to <10 mm. PR was a ≥30% decrease in the sum of the diameters of target lesions. The percentage of participants with objective response=(number of participants whose best overall response achieved was CR or PR/number of participants treated)*100.

    3. Duration of Response [Time of first response to measured PD (up to Month 23.0)]

      Duration of response was defined using RECIST v. 1.1 criteria as the time from the date criteria were met for the first objectively recorded CR or PR until the first date criteria for PD were met or death from any cause. CR was the disappearance of all lesions and pathological lymph node reduction in the short axis to <10 mm. PR was a ≥30% decrease in the sum of the diameters of target lesions. PD was a ≥20% increase in the sum of the diameters of target lesions with the sum demonstrating an absolute increase of ≥5 mm; the appearance of ≥1 new lesions or unequivocal progression of non-target lesions. Participants who were not known to have died and who did not have PD were censored at the date of the last tumor assessment prior to the date of any subsequent systemic anticancer therapy.

    4. Time to Disease Progression (TTP) [Randomization to measured PD (up to Month 25.0)]

      TTP was defined using RECIST v. 1.1 as the time from study randomization to the first date of PD. PD was a ≥20% increase in the sum of the diameters of target lesions with the sum demonstrating an absolute increase of ≥5 mm; the appearance of ≥1 new lesions or unequivocal progression of non-target lesions. TTP was censored at the date of last adequate tumor assessment if death was due to causes other than PD.

    5. Number of Participants With Treatment-Emergent Anti-Ramucirumab Antibodies [Months 1, 2, 4, 6, and 8]

      Participants with treatment-emergent anti-ramucirumab antibodies were participants with a 4-fold increase (2 dilution increase) in immunogenicity titer over baseline titer, or participants who tested negative at baseline and positive post-baseline (at titer of ≥1:20).

    Other Outcome Measures

    1. Number of Participants With Adverse Events (AEs) [Baseline through study completion (up to Month 28.3)]

      Reported are the number of participants who had ramucirumab/placebo-related: AEs, serious AEs (SAEs), AEs based on common terminology criteria for adverse events (CTCAE) ≥Grade 3, AEs = CTCAE Grade 5, as well as, AEs leading to treatment discontinuation and AEs resulting in death. A summary of serious and other non-serious AEs regardless of causality is located in the Reported Adverse Events module.

    Eligibility Criteria

    Criteria

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

    • Histologic or cytologic confirmation of adenocarcinoma of the esophagus, gastroesophageal junction (GEJ), or stomach

    • Metastatic or locally advanced, unresectable disease at time of study entry

    • Provided signed informed consent and is amenable to compliance with protocol schedules and testing

    • Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-1 at study entry

    • Adequate renal, hematological, and hepatic function

    • Measurable or non-measurable disease at the time of study entry

    • Resolution to Grade less than or equal to 1 by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.0, of all clinically significant toxic effects of prior locoregional therapy, surgery, or other anticancer therapy, except where otherwise mentioned in the eligibility criteria

    • Eligible participants of reproductive potential (both sexes) must agree to use adequate contraceptive methods (hormonal or barrier methods) during the study period and at least 12 weeks after the last dose of study therapy

    • Life expectancy of greater than or equal to 3 months

    • Willingness to provide blood and tissue samples for research purposes. Submission of tumor specimen is mandatory for participation in this study, if a histologic, paraffin-embedded specimen exists (either from a surgical resection or biopsy); submission of paraffin block or a minimum of 8 unstained slides is required if sufficient sample. NOTE: If insufficient additional tissue exists (that is, all tissue has been utilized for prior diagnostic purposes), participation in the study is allowable without the requirement for an additional biopsy; this situation must be discussed with the study principal investigator and/or the ImClone medical monitor or designee.

    Exclusion Criteria:

    • The participant has received prior first-line systemic therapy for advanced/unresectable and/or metastatic disease (prior adjuvant or neo-adjuvant therapy is permitted)

    • Previous or concurrent malignancy except for basal or squamous cell skin cancer and/or in situ carcinoma of the cervix, or other solid tumors treated curatively and without evidence of recurrence for at least 3 years prior to study entry

    • Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the participant ineligible for entry into this study

    • The participant is receiving chronic therapy with nonsteroidal anti-inflammatory agents (NSAIDs; for example, indomethacin, ibuprofen, naproxen, or similar agents) or other antiplatelet agents (for example, clopidogrel, ticlopidine, dipyridamole, anagrelide). Aspirin use at doses up to 325 milligrams per day (mg/day) is permitted.

    • The participant has significant third-space fluid retention (for example, ascites or pleural effusion), and is not amenable for required repeated drainage

    • The participant is pregnant or breastfeeding

    • Uncontrolled intercurrent illness including, but not limited to, active or uncontrolled clinically serious infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled thromboembolic, or hemorrhagic disorder, psychiatric illness/social situations, or other co-morbid systemic illnesses, or other severe concurrent disease

    • Immunocompromised participants including participants known to be human immunodeficiency virus (HIV) positive.

    • Progressive disease less than or equal to 12 months of completing platinum or 5-FU treatment, including capecitabine, if given previously in the perioperative (adjuvant or neoadjuvant) setting

    • Current or recent (within 28 days prior to randomization) treatment with an investigational drug that has not received regulatory approval for any indication at the time of study entry, or participation in another interventional clinical trial. Participants participating in surveys or observational studies are eligible to participate in this study.

    • Are currently enrolled in, or discontinued within the last 28 days from, a clinical trial involving ramucirumab drug product (DP), or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study

    • Received prior therapy with an antiangiogenic agent (including but not limited to bevacizumab, sunitinib, or sorafenib)

    • Major surgical procedure or significant traumatic injury less than 28 days prior to randomization, or anticipation of need for elective or planned major surgical procedure during the course of the study. Subcutaneous venous access device placement within 7 days prior to randomization

    • Clinically significant peripheral neuropathy at the time of registration

    • Known central nervous system metastases that are symptomatic or untreated

    • New York Heart Association (NYHA) classification III-IV congestive heart failure

    • Greater than normal risk of bleeding or coagulopathy in the absence of therapeutic anticoagulation; Grade 3/4 gastrointestinal bleeding within 3 months prior to registration; active bleeding (that is, within 14 days prior to first dose of study therapy); or pathological condition present that carries a high risk of bleeding (for example, tumor involving major vessels or known varices)

    • Participant has experienced any arterial thromboembolic events, including but not limited to myocardial infarction, stroke, transient ischemic attack (TIA), cerebrovascular accident, or unstable angina, less than or equal to 6 months prior to registration

    • Clinically significant vascular disease (for example, aortic aneurysm, aortic dissection) for which more than minimal intervention is being administered or planned

    • History of hypertensive crisis or hypertensive encephalopathy or current poorly-controlled hypertension despite standard medical management

    • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess less than 6 months prior to registration

    • Known hypersensitivity to any of the treatment components of modified FOLFOX6 (mFOLFOX6) (oxaliplatin, 5-FU, and leucovorin) or ramucirumab DP

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 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. Anchorage Alaska United States 99508
    2 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. Scottsdale Arizona United States 85259
    3 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. Alhambra California United States 91801
    4 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. Bakersfield California United States 93309
    5 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. Fullerton California United States 92835
    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. Los Angeles California United States 90024
    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. Northridge California United States 91325
    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. Redondo Beach California United States 90277
    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. Santa Barbara California United States 93105
    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. Santa Monica California United States 93454
    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. Denver Colorado United States 80218
    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. Grand Junction Colorado United States 81501
    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. Washington District of Columbia United States 20007
    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. Englewood Florida United States 34223
    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. Pembroke Pines Florida United States 33028
    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. West Palm Beach Florida United States 33401
    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. Terre Haute Indiana United States 47802
    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. Sioux City Iowa United States 51101
    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. Wichita Kansas United States 67214
    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. New Orleans Louisiana United States 70121
    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. Lewiston Maine United States 04240
    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. Baltimore Maryland United States 21201
    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. Burlington Massachusetts United States 01805
    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. Springfield Massachusetts United States 01107
    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. Ann Arbor Michigan United States 48106
    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. Detroit Michigan United States 48201
    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. Grand Rapids Michigan United States 49503
    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. Kalamazoo Michigan United States 49007
    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. Duluth Minnesota United States 55805
    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. Rochester Minnesota United States 55905
    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. St Louis Park Minnesota United States 55416
    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. St Louis Missouri United States 63110
    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. Billings Montana United States 59101
    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. Bozeman Montana United States 59715
    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. Omaha Nebraska United States 68106
    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. Las Vegas Nevada United States 89169
    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. Hackensack New Jersey United States 07601
    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. Bronx New York United States 10467
    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. Cincinnati Ohio United States 45242
    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. Dayton Ohio United States 45420
    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. Oklahoma City Oklahoma United States 73104
    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. Danville Pennsylvania United States 17822
    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. Dunmore Pennsylvania United States 18512
    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. Philadelphia Pennsylvania United States 19141
    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. Charleston South Carolina United States 29425
    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. Columbia South Carolina United States 29210
    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. Spartanburg South Carolina United States 29303
    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. Chattanooga Tennessee United States 37404
    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. Nashville Tennessee United States 37203
    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. Salt Lake City Utah United States 84112
    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. Richmond Virginia United States 23230
    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. Kirkland Washington United States 98034
    53 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. Mount Vernon Washington United States 98273
    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. Seattle Washington United States 98112
    55 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. Tacoma Washington United States 98405
    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. Wenatchee Washington United States 98801
    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. Madison Wisconsin United States 53792
    58 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. Marshfield Wisconsin United States 54449

    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:
    NCT01246960
    Other Study ID Numbers:
    • 14057
    • I4T-MC-JVBT
    First Posted:
    Nov 24, 2010
    Last Update Posted:
    Oct 8, 2014
    Last Verified:
    Oct 1, 2014
    Keywords provided by Eli Lilly and Company
    cancer
    stomach
    esophagus
    gastroesophageal
    Additional relevant MeSH terms:
    Stomach Neoplasms
    Leucovorin
    Fluorouracil
    Oxaliplatin
    Ramucirumab

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Ramucirumab and mFOLFOX6 Placebo and mFOLFOX6
    Arm/Group Description Ramucirumab: 8 milligrams per kilogram (mg/kg) intravenous infusion administered on Day 1 of each cycle (14 days/cycle). In Cycles 1 and 2, there was a 1-hour observation prior to administering modified FOLFOX6 (mFOLFOX6). mFOLFOX6: Administered intravenously per manufacturer's instructions for each drug substance on Day 1 of each cycle (14 days/cycle). Oxaliplatin 85 milligrams per square meter (mg/m^2) Leucovorin 400 mg/m^2 5-Fluorouracil (5-FU) 400 mg/m^2 bolus 5-FU 2400 mg/m^2 continuous given over 46-48 hours Participants received study treatment every 2 weeks until disease progression, unacceptable toxicity, or another withdrawal criterion was met. Placebo: intravenous infusion administered on Day 1 of each cycle (14 days/cycle). In Cycles 1 and 2, there was a 1-hour observation prior to administering mFOLFOX6. mFOLFOX6: Administered intravenously per manufacturer's instructions for each drug substance on Day 1 of each cycle (14 days/cycle). Oxaliplatin 85 mg/m^2 Leucovorin 400 mg/m^2 5-FU 400 mg/m^2 bolus 5-FU 2400 mg/m^2 continuous given over 46-48 hours Participants received study treatment every 2 weeks until disease progression, unacceptable toxicity, or another withdrawal criterion was met.
    Period Title: Overall Study
    STARTED 84 84
    Received Any Quantity of Study Drug 82 80
    COMPLETED 78 80
    NOT COMPLETED 6 4

    Baseline Characteristics

    Arm/Group Title Ramucirumab and mFOLFOX6 Placebo and mFOLFOX6 Total
    Arm/Group Description Ramucirumab: 8 mg/kg intravenous infusion administered on Day 1 of each cycle (14 days/cycle). In Cycles 1 and 2, there was a 1-hour observation prior to administering mFOLFOX6. mFOLFOX6: Administered intravenously per manufacturer's instructions for each drug substance on Day 1 of each cycle (14 days/cycle). Oxaliplatin: 85 mg/m^2 Leucovorin: 400 mg/m^2 5-FU: 400 mg/m^2 bolus 5-FU: 2400 mg/m^2 continuous given over 46-48 hours Participants received study treatment every 2 weeks until disease progression, unacceptable toxicity, or another withdrawal criterion was met. Placebo: intravenous infusion administered on Day 1 of each cycle (14 days/cycle). In Cycles 1 and 2, there was a 1-hour observation prior to administering mFOLFOX6. mFOLFOX6: Administered intravenously per manufacturer's instructions for each drug substance on Day 1 of each cycle (14 days/cycle). Oxaliplatin: 85 mg/m^2 Leucovorin: 400 mg/m^2 5-FU: 400 mg/m^2 bolus 5-FU: 2400 mg/m^2 continuous given over 46-48 hours Participants received study treatment every 2 weeks until disease progression, unacceptable toxicity, or another withdrawal criterion was met. Total of all reporting groups
    Overall Participants 84 84 168
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    42
    50%
    56
    66.7%
    98
    58.3%
    >=65 years
    42
    50%
    28
    33.3%
    70
    41.7%
    Sex: Female, Male (Count of Participants)
    Female
    21
    25%
    23
    27.4%
    44
    26.2%
    Male
    63
    75%
    61
    72.6%
    124
    73.8%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    4
    4.8%
    9
    10.7%
    13
    7.7%
    Not Hispanic or Latino
    80
    95.2%
    75
    89.3%
    155
    92.3%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Race/Ethnicity, Customized (participants) [Number]
    Asian
    2
    2.4%
    4
    4.8%
    6
    3.6%
    Native Hawaiian or Other Pacific Islander
    2
    2.4%
    1
    1.2%
    3
    1.8%
    Black or African American
    3
    3.6%
    3
    3.6%
    6
    3.6%
    White
    77
    91.7%
    76
    90.5%
    153
    91.1%
    Region of Enrollment (participants) [Number]
    United States
    84
    100%
    84
    100%
    168
    100%

    Outcome Measures

    1. Primary Outcome
    Title Progression-Free Survival (PFS)
    Description PFS was defined using Response Evaluation Criteria in Solid Tumors [RECIST version (v.) 1.1] as the time from randomization to the first observation of progressive disease (PD) or death due to any cause, whichever came first. PD was a ≥20% increase in the sum of the diameters of target lesions with the sum demonstrating an absolute increase of ≥5 millimeters (mm); the appearance of ≥1 new lesions or unequivocal progression of non-target lesions. If a participant did not have a baseline disease assessment, PFS time was censored at the randomization date, regardless of whether or not PD or death was observed. Participants not known to have died or have objective PD were censored at the last post-baseline radiological assessment date.
    Time Frame Randomization to measured PD or date of death from any cause (up to Month 25.0)

    Outcome Measure Data

    Analysis Population Description
    ITT population: all randomized participants. Fourteen participants in the Ramucirumab and mFOLFOX6 treatment arm and 15 participants in the Placebo and mFOLFOX6 treatment arm were censored.
    Arm/Group Title Ramucirumab and mFOLFOX6 Placebo and mFOLFOX6
    Arm/Group Description Ramucirumab: 8 mg/kg intravenous infusion administered on Day 1 of each cycle (14 days/cycle). In Cycles 1 and 2, there was a 1-hour observation prior to administering mFOLFOX6. mFOLFOX6: Administered intravenously per manufacturer's instructions for each drug substance on Day 1 of each cycle (14 days/cycle). Oxaliplatin: 85 mg/m^2 Leucovorin: 400 mg/m^2 5-FU: 400 mg/m^2 bolus 5-FU: 2400 mg/m^2 continuous given over 46-48 hours Participants received study treatment every 2 weeks until disease progression, unacceptable toxicity, or another withdrawal criterion was met. Placebo: intravenous infusion administered on Day 1 of each cycle (14 days/cycle). In Cycles 1 and 2, there was a 1-hour observation prior to administering mFOLFOX6. mFOLFOX6: Administered intravenously per manufacturer's instructions for each drug substance on Day 1 of each cycle (14 days/cycle). Oxaliplatin: 85 mg/m^2 Leucovorin: 400 mg/m^2 5-FU: 400 mg/m^2 bolus 5-FU: 2400 mg/m^2 continuous given over 46-48 hours Participants received study treatment every 2 weeks until disease progression, unacceptable toxicity, or another withdrawal criterion was met.
    Measure Participants 84 84
    Median (95% Confidence Interval) [months]
    6.4
    6.7
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ramucirumab and mFOLFOX6, Placebo and mFOLFOX6
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.886
    Comments
    Method Stratified Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.98
    Confidence Interval (2-Sided) 95%
    0.69 to 1.37
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Overall Survival (OS)
    Description OS was defined as the time from randomization to death due to any cause. OS was censored at the date of the last follow-up visit for participants who were alive or lost to follow-up.
    Time Frame Randomization to date of death from any cause (up to Month 28.3)

    Outcome Measure Data

    Analysis Population Description
    ITT population: all randomized participants. Twenty-seven participants in the Ramucirumab and mFOLFOX6 treatment arm and 32 participants in the Placebo and mFOLFOX6 treatment arm were censored.
    Arm/Group Title Ramucirumab and mFOLFOX6 Placebo and mFOLFOX6
    Arm/Group Description Ramucirumab: 8 mg/kg intravenous infusion administered on Day 1 of each cycle (14 days/cycle). In Cycles 1 and 2, there was a 1-hour observation prior to administering mFOLFOX6. mFOLFOX6: Administered intravenously per manufacturer's instructions for each drug substance on Day 1 of each cycle (14 days/cycle). Oxaliplatin: 85 mg/m^2 Leucovorin: 400 mg/m^2 5-FU: 400 mg/m^2 bolus 5-FU: 2400 mg/m^2 continuous given over 46-48 hours Participants received study treatment every 2 weeks until disease progression, unacceptable toxicity, or another withdrawal criterion was met. Placebo: intravenous infusion administered on Day 1 of each cycle (14 days/cycle). In Cycles 1 and 2, there was a 1-hour observation prior to administering mFOLFOX6. mFOLFOX6: Administered intravenously per manufacturer's instructions for each drug substance on Day 1 of each cycle (14 days/cycle). Oxaliplatin: 85 mg/m^2 Leucovorin: 400 mg/m^2 5-FU: 400 mg/m^2 bolus 5-FU: 2400 mg/m^2 continuous given over 46-48 hours Participants received study treatment every 2 weeks until disease progression, unacceptable toxicity, or another withdrawal criterion was met.
    Measure Participants 84 84
    Median (95% Confidence Interval) [months]
    11.7
    11.5
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ramucirumab and mFOLFOX6, Placebo and mFOLFOX6
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.712
    Comments
    Method Stratified Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.08
    Confidence Interval (2-Sided) 95%
    0.73 to 1.58
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Secondary Outcome
    Title Percentage of Participants Achieving an Objective Response (Objective Response Rate)
    Description The percentage of participants who achieved a best overall response of partial response (PR) or complete response (CR) is reported. Response was defined using RECIST, v. 1.1 criteria. CR was the disappearance of all lesions and pathological lymph node reduction in the short axis to <10 mm. PR was a ≥30% decrease in the sum of the diameters of target lesions. The percentage of participants with objective response=(number of participants whose best overall response achieved was CR or PR/number of participants treated)*100.
    Time Frame Randomization to measured PD (up to Month 23.0)

    Outcome Measure Data

    Analysis Population Description
    ITT population: all randomized participants.
    Arm/Group Title Ramucirumab and mFOLFOX6 Placebo and mFOLFOX6
    Arm/Group Description Ramucirumab: 8 mg/kg intravenous infusion administered on Day 1 of each cycle (14 days/cycle). In Cycles 1 and 2, there was a 1-hour observation prior to administering mFOLFOX6. mFOLFOX6: Administered intravenously per manufacturer's instructions for each drug substance on Day 1 of each cycle (14 days/cycle). Oxaliplatin: 85 mg/m^2 Leucovorin: 400 mg/m^2 5-FU: 400 mg/m^2 bolus 5-FU: 2400 mg/m^2 continuous given over 46-48 hours Participants received study treatment every 2 weeks until disease progression, unacceptable toxicity, or another withdrawal criterion was met. Placebo: intravenous infusion administered on Day 1 of each cycle (14 days/cycle). In Cycles 1 and 2, there was a 1-hour observation prior to administering mFOLFOX6. mFOLFOX6: Administered intravenously per manufacturer's instructions for each drug substance on Day 1 of each cycle (14 days/cycle). Oxaliplatin: 85 mg/m^2 Leucovorin: 400 mg/m^2 5-FU: 400 mg/m^2 bolus 5-FU: 2400 mg/m^2 continuous given over 46-48 hours Participants received study treatment every 2 weeks until disease progression, unacceptable toxicity, or another withdrawal criterion was met.
    Measure Participants 84 84
    Number (95% Confidence Interval) [percentage of participants]
    45.2
    53.8%
    46.4
    55.2%
    4. Secondary Outcome
    Title Duration of Response
    Description Duration of response was defined using RECIST v. 1.1 criteria as the time from the date criteria were met for the first objectively recorded CR or PR until the first date criteria for PD were met or death from any cause. CR was the disappearance of all lesions and pathological lymph node reduction in the short axis to <10 mm. PR was a ≥30% decrease in the sum of the diameters of target lesions. PD was a ≥20% increase in the sum of the diameters of target lesions with the sum demonstrating an absolute increase of ≥5 mm; the appearance of ≥1 new lesions or unequivocal progression of non-target lesions. Participants who were not known to have died and who did not have PD were censored at the date of the last tumor assessment prior to the date of any subsequent systemic anticancer therapy.
    Time Frame Time of first response to measured PD (up to Month 23.0)

    Outcome Measure Data

    Analysis Population Description
    Randomized participants who achieved an objective response of CR or PR. Eight participants in the Ramucirumab and mFOLFOX6 treatment arm and 8 participants in the Placebo and mFOLFOX6 treatment arm were censored.
    Arm/Group Title Ramucirumab and mFOLFOX6 Placebo and mFOLFOX6
    Arm/Group Description Ramucirumab: 8 mg/kg intravenous infusion administered on Day 1 of each cycle (14 days/cycle). In Cycles 1 and 2, there was a 1-hour observation prior to administering mFOLFOX6. mFOLFOX6: Administered intravenously per manufacturer's instructions for each drug substance on Day 1 of each cycle (14 days/cycle). Oxaliplatin: 85 mg/m^2 Leucovorin: 400 mg/m^2 5-FU: 400 mg/m^2 bolus 5-FU: 2400 mg/m^2 continuous given over 46-48 hours Participants received study treatment every 2 weeks until disease progression, unacceptable toxicity, or another withdrawal criterion was met. Placebo: intravenous infusion administered on Day 1 of each cycle (14 days/cycle). In Cycles 1 and 2, there was a 1-hour observation prior to administering mFOLFOX6. mFOLFOX6: Administered intravenously per manufacturer's instructions for each drug substance on Day 1 of each cycle (14 days/cycle). Oxaliplatin: 85 mg/m^2 Leucovorin: 400 mg/m^2 5-FU: 400 mg/m^2 bolus 5-FU: 2400 mg/m^2 continuous given over 46-48 hours Participants received study treatment every 2 weeks until disease progression, unacceptable toxicity, or another withdrawal criterion was met.
    Measure Participants 38 39
    Median (95% Confidence Interval) [months]
    7.4
    5.8
    5. Secondary Outcome
    Title Time to Disease Progression (TTP)
    Description TTP was defined using RECIST v. 1.1 as the time from study randomization to the first date of PD. PD was a ≥20% increase in the sum of the diameters of target lesions with the sum demonstrating an absolute increase of ≥5 mm; the appearance of ≥1 new lesions or unequivocal progression of non-target lesions. TTP was censored at the date of last adequate tumor assessment if death was due to causes other than PD.
    Time Frame Randomization to measured PD (up to Month 25.0)

    Outcome Measure Data

    Analysis Population Description
    ITT population: all randomized participants. Thirty-five participants in the Ramucirumab and mFOLFOX6 treatment arm and 31 participants in the Placebo and mFOLFOX6 treatment arm were censored.
    Arm/Group Title Ramucirumab and mFOLFOX6 Placebo and mFOLFOX6
    Arm/Group Description Ramucirumab: 8 mg/kg intravenous infusion administered on Day 1 of each cycle (14 days/cycle). In Cycles 1 and 2, there was a 1-hour observation prior to administering mFOLFOX6. mFOLFOX6: Administered intravenously per manufacturer's instructions for each drug substance on Day 1 of each cycle (14 days/cycle). Oxaliplatin: 85 mg/m^2 Leucovorin: 400 mg/m^2 5-FU: 400 mg/m^2 bolus 5-FU: 2400 mg/m^2 continuous given over 46-48 hours Participants received study treatment every 2 weeks until disease progression, unacceptable toxicity, or another withdrawal criterion was met. Placebo: intravenous infusion administered on Day 1 of each cycle (14 days/cycle). In Cycles 1 and 2, there was a 1-hour observation prior to administering mFOLFOX6. mFOLFOX6: Administered intravenously per manufacturer's instructions for each drug substance on Day 1 of each cycle (14 days/cycle). Oxaliplatin: 85 mg/m^2 Leucovorin: 400 mg/m^2 5-FU: 400 mg/m^2 bolus 5-FU: 2400 mg/m^2 continuous given over 46-48 hours Participants received study treatment every 2 weeks until disease progression, unacceptable toxicity, or another withdrawal criterion was met.
    Measure Participants 84 84
    Median (Full Range) [months]
    8.7
    7.1
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ramucirumab and mFOLFOX6, Placebo and mFOLFOX6
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.516
    Comments
    Method Stratified Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.88
    Confidence Interval (2-Sided) 95%
    0.59 to 1.30
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    6. Secondary Outcome
    Title Number of Participants With Treatment-Emergent Anti-Ramucirumab Antibodies
    Description Participants with treatment-emergent anti-ramucirumab antibodies were participants with a 4-fold increase (2 dilution increase) in immunogenicity titer over baseline titer, or participants who tested negative at baseline and positive post-baseline (at titer of ≥1:20).
    Time Frame Months 1, 2, 4, 6, and 8

    Outcome Measure Data

    Analysis Population Description
    Randomized participants who received any quantity of ramucirumab or placebo, and were evaluated for the presence of anti-ramucirumab antibodies.
    Arm/Group Title Ramucirumab and mFOLFOX6 Placebo and mFOLFOX6
    Arm/Group Description Ramucirumab: 8 mg/kg intravenous infusion administered on Day 1 of each cycle (14 days/cycle). In Cycles 1 and 2, there was a 1-hour observation prior to administering mFOLFOX6. mFOLFOX6: Administered intravenously per manufacturer's instructions for each drug substance on Day 1 of each cycle (14 days/cycle). Oxaliplatin: 85 mg/m^2 Leucovorin: 400 mg/m^2 5-FU: 400 mg/m^2 bolus 5-FU: 2400 mg/m^2 continuous given over 46-48 hours Participants received study treatment every 2 weeks until disease progression, unacceptable toxicity, or another withdrawal criterion was met. Placebo: intravenous infusion administered on Day 1 of each cycle (14 days/cycle). In Cycles 1 and 2, there was a 1-hour observation prior to administering mFOLFOX6. mFOLFOX6: Administered intravenously per manufacturer's instructions for each drug substance on Day 1 of each cycle (14 days/cycle). Oxaliplatin: 85 mg/m^2 Leucovorin: 400 mg/m^2 5-FU: 400 mg/m^2 bolus 5-FU: 2400 mg/m^2 continuous given over 46-48 hours Participants received study treatment every 2 weeks until disease progression, unacceptable toxicity, or another withdrawal criterion was met.
    Measure Participants 81 77
    Number [participants]
    0
    0%
    1
    1.2%
    7. Other Pre-specified Outcome
    Title Number of Participants With Adverse Events (AEs)
    Description Reported are the number of participants who had ramucirumab/placebo-related: AEs, serious AEs (SAEs), AEs based on common terminology criteria for adverse events (CTCAE) ≥Grade 3, AEs = CTCAE Grade 5, as well as, AEs leading to treatment discontinuation and AEs resulting in death. A summary of serious and other non-serious AEs regardless of causality is located in the Reported Adverse Events module.
    Time Frame Baseline through study completion (up to Month 28.3)

    Outcome Measure Data

    Analysis Population Description
    Safety population: randomized participants who received any quantity of study drug (Ramucirumab, mFOLFOX6, or placebo).
    Arm/Group Title Ramucirumab and mFOLFOX6 Placebo and mFOLFOX6
    Arm/Group Description Ramucirumab: 8 mg/kg intravenous infusion administered on Day 1 of each cycle (14 days/cycle). In Cycles 1 and 2, there was a 1-hour observation prior to administering mFOLFOX6. mFOLFOX6: Administered intravenously per manufacturer's instructions for each drug substance on Day 1 of each cycle (14 days/cycle). Oxaliplatin: 85 mg/m^2 Leucovorin: 400 mg/m^2 5-FU: 400 mg/m^2 bolus 5-FU: 2400 mg/m^2 continuous given over 46-48 hours Participants received study treatment every 2 weeks until disease progression, unacceptable toxicity, or another withdrawal criterion was met. Placebo: intravenous infusion administered on Day 1 of each cycle (14 days/cycle). In Cycles 1 and 2, there was a 1-hour observation prior to administering mFOLFOX6. mFOLFOX6: Administered intravenously per manufacturer's instructions for each drug substance on Day 1 of each cycle (14 days/cycle). Oxaliplatin: 85 mg/m^2 Leucovorin: 400 mg/m^2 5-FU: 400 mg/m^2 bolus 5-FU: 2400 mg/m^2 continuous given over 46-48 hours Participants received study treatment every 2 weeks until disease progression, unacceptable toxicity, or another withdrawal criterion was met.
    Measure Participants 82 80
    Any Ramucirumab/Placebo-Related AE
    64
    76.2%
    64
    76.2%
    Any Ramucirumab/Placebo-Related SAE
    10
    11.9%
    12
    14.3%
    Any Ramucirumab/Placebo-Related ≥Grade 3 AE
    36
    42.9%
    33
    39.3%
    Any Ramucirumab/Placebo-Related Grade 5 AE
    0
    0%
    3
    3.6%
    Any AE Leading to Treatment Discontinuation
    18
    21.4%
    5
    6%
    Any AE with Outcome of Death
    5
    6%
    2
    2.4%

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title Ramucirumab and mFOLFOX6 Placebo and mFOLFOX6
    Arm/Group Description Ramucirumab: 8 mg/kg intravenous infusion administered on Day 1 of each cycle (14 days/cycle). In Cycles 1 and 2, there was a 1-hour observation prior to administering mFOLFOX6. mFOLFOX6: Administered intravenously per manufacturer's instructions for each drug substance on Day 1 of each cycle (14 days/cycle). Oxaliplatin: 85 mg/m^2 Leucovorin: 400 mg/m^2 5-FU: 400 mg/m^2 bolus 5-FU: 2400 mg/m^2 continuous given over 46-48 hours Participants received study treatment every 2 weeks until disease progression, unacceptable toxicity, or another withdrawal criterion was met. Placebo: intravenous infusion administered on Day 1 of each cycle (14 days/cycle). In Cycles 1 and 2, there was a 1-hour observation prior to administering mFOLFOX6. mFOLFOX6: Administered intravenously per manufacturer's instructions for each drug substance on Day 1 of each cycle (14 days/cycle). Oxaliplatin: 85 mg/m^2 Leucovorin: 400 mg/m^2 5-FU: 400 mg/m^2 bolus 5-FU: 2400 mg/m^2 continuous given over 46-48 hours Participants received study treatment every 2 weeks until disease progression, unacceptable toxicity, or another withdrawal criterion was met.
    All Cause Mortality
    Ramucirumab and mFOLFOX6 Placebo and mFOLFOX6
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Ramucirumab and mFOLFOX6 Placebo and mFOLFOX6
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 48/82 (58.5%) 32/80 (40%)
    Blood and lymphatic system disorders
    Anaemia 3/82 (3.7%) 5 0/80 (0%) 0
    Febrile neutropenia 3/82 (3.7%) 3 2/80 (2.5%) 2
    Neutropenia 2/82 (2.4%) 3 0/80 (0%) 0
    Thrombocytopenia 1/82 (1.2%) 1 0/80 (0%) 0
    Cardiac disorders
    Acute myocardial infarction 1/82 (1.2%) 1 0/80 (0%) 0
    Arteriospasm coronary 1/82 (1.2%) 1 0/80 (0%) 0
    Atrial fibrillation 0/82 (0%) 0 2/80 (2.5%) 2
    Bradycardia 0/82 (0%) 0 1/80 (1.3%) 1
    Cardiac tamponade 1/82 (1.2%) 1 1/80 (1.3%) 1
    Myocardial infarction 1/82 (1.2%) 1 0/80 (0%) 0
    Pericardial effusion 1/82 (1.2%) 1 0/80 (0%) 0
    Sinus bradycardia 1/82 (1.2%) 1 0/80 (0%) 0
    Gastrointestinal disorders
    Abdominal distension 1/82 (1.2%) 1 0/80 (0%) 0
    Abdominal pain 1/82 (1.2%) 1 0/80 (0%) 0
    Ascites 1/82 (1.2%) 1 0/80 (0%) 0
    Constipation 1/82 (1.2%) 1 1/80 (1.3%) 1
    Dysphagia 1/82 (1.2%) 2 1/80 (1.3%) 1
    Enteritis 0/82 (0%) 0 1/80 (1.3%) 1
    Gastric haemorrhage 2/82 (2.4%) 2 0/80 (0%) 0
    Gastric perforation 1/82 (1.2%) 1 0/80 (0%) 0
    Gastrointestinal disorder 1/82 (1.2%) 1 0/80 (0%) 0
    Gastrointestinal haemorrhage 4/82 (4.9%) 4 3/80 (3.8%) 3
    Gastrointestinal obstruction 0/82 (0%) 0 1/80 (1.3%) 1
    Ileus 1/82 (1.2%) 2 1/80 (1.3%) 1
    Intestinal obstruction 1/82 (1.2%) 1 0/80 (0%) 0
    Nausea 5/82 (6.1%) 6 2/80 (2.5%) 2
    Oesophageal obstruction 1/82 (1.2%) 2 0/80 (0%) 0
    Oesophageal stenosis 1/82 (1.2%) 1 0/80 (0%) 0
    Oesophagitis 2/82 (2.4%) 2 0/80 (0%) 0
    Pancreatitis 1/82 (1.2%) 1 0/80 (0%) 0
    Small intestinal haemorrhage 0/82 (0%) 0 1/80 (1.3%) 1
    Upper gastrointestinal haemorrhage 0/82 (0%) 0 1/80 (1.3%) 1
    Vomiting 3/82 (3.7%) 4 2/80 (2.5%) 2
    General disorders
    Asthenia 1/82 (1.2%) 1 0/80 (0%) 0
    Death 0/82 (0%) 0 2/80 (2.5%) 2
    Device dislocation 0/82 (0%) 0 2/80 (2.5%) 2
    Disease progression 1/82 (1.2%) 1 3/80 (3.8%) 3
    Multi-organ failure 1/82 (1.2%) 1 0/80 (0%) 0
    Non-cardiac chest pain 1/82 (1.2%) 1 1/80 (1.3%) 1
    Pain 1/82 (1.2%) 1 1/80 (1.3%) 1
    Pyrexia 2/82 (2.4%) 3 1/80 (1.3%) 1
    Hepatobiliary disorders
    Bile duct stone 0/82 (0%) 0 1/80 (1.3%) 1
    Cholangitis 0/82 (0%) 0 1/80 (1.3%) 1
    Cholecystitis 1/82 (1.2%) 1 0/80 (0%) 0
    Hepatic failure 1/82 (1.2%) 1 0/80 (0%) 0
    Jaundice cholestatic 0/82 (0%) 0 1/80 (1.3%) 1
    Immune system disorders
    Anaphylactic reaction 0/82 (0%) 0 1/80 (1.3%) 1
    Infections and infestations
    Appendicitis 1/82 (1.2%) 1 0/80 (0%) 0
    Bacteraemia 0/82 (0%) 0 2/80 (2.5%) 2
    Catheter site infection 1/82 (1.2%) 1 0/80 (0%) 0
    Cellulitis 1/82 (1.2%) 1 0/80 (0%) 0
    Gastroenteritis 0/82 (0%) 0 1/80 (1.3%) 1
    Kidney infection 1/82 (1.2%) 1 0/80 (0%) 0
    Lung infection 1/82 (1.2%) 1 0/80 (0%) 0
    Perirectal abscess 0/82 (0%) 0 1/80 (1.3%) 1
    Peritonitis 1/82 (1.2%) 1 0/80 (0%) 0
    Pneumonia 3/82 (3.7%) 3 0/80 (0%) 0
    Pyelonephritis 1/82 (1.2%) 1 0/80 (0%) 0
    Respiratory syncytial virus infection 1/82 (1.2%) 1 0/80 (0%) 0
    Sepsis 3/82 (3.7%) 3 3/80 (3.8%) 3
    Urinary tract infection 0/82 (0%) 0 1/80 (1.3%) 1
    Injury, poisoning and procedural complications
    Anastomotic ulcer haemorrhage 0/82 (0%) 0 1/80 (1.3%) 1
    Foot fracture 1/82 (1.2%) 1 0/80 (0%) 0
    Laceration 1/82 (1.2%) 1 0/80 (0%) 0
    Subdural haemorrhage 0/82 (0%) 0 1/80 (1.3%) 1
    Urostomy complication 0/82 (0%) 0 1/80 (1.3%) 1
    Investigations
    International normalised ratio increased 0/82 (0%) 0 1/80 (1.3%) 1
    Metabolism and nutrition disorders
    Dehydration 3/82 (3.7%) 3 1/80 (1.3%) 1
    Failure to thrive 0/82 (0%) 0 1/80 (1.3%) 1
    Hypophagia 1/82 (1.2%) 2 0/80 (0%) 0
    Musculoskeletal and connective tissue disorders
    Arthralgia 1/82 (1.2%) 1 0/80 (0%) 0
    Polyarthritis 1/82 (1.2%) 1 0/80 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Malignant pleural effusion 0/82 (0%) 0 1/80 (1.3%) 1
    Meningioma 1/82 (1.2%) 1 0/80 (0%) 0
    Metastases to central nervous system 0/82 (0%) 0 1/80 (1.3%) 1
    Oesophageal carcinoma 0/82 (0%) 0 1/80 (1.3%) 1
    Nervous system disorders
    Depressed level of consciousness 1/82 (1.2%) 1 0/80 (0%) 0
    Headache 3/82 (3.7%) 3 0/80 (0%) 0
    Memory impairment 1/82 (1.2%) 1 0/80 (0%) 0
    Parkinsonism 0/82 (0%) 0 1/80 (1.3%) 1
    Syncope 3/82 (3.7%) 3 1/80 (1.3%) 1
    Psychiatric disorders
    Confusional state 2/82 (2.4%) 2 1/80 (1.3%) 1
    Renal and urinary disorders
    Hydronephrosis 1/82 (1.2%) 1 0/80 (0%) 0
    Renal failure acute 0/82 (0%) 0 1/80 (1.3%) 1
    Renal injury 1/82 (1.2%) 1 0/80 (0%) 0
    Urinary retention 0/82 (0%) 0 1/80 (1.3%) 1
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure 1/82 (1.2%) 1 0/80 (0%) 0
    Asthma 1/82 (1.2%) 1 0/80 (0%) 0
    Atelectasis 0/82 (0%) 0 1/80 (1.3%) 1
    Chronic obstructive pulmonary disease 2/82 (2.4%) 3 0/80 (0%) 0
    Dyspnoea 2/82 (2.4%) 2 2/80 (2.5%) 2
    Emphysema 1/82 (1.2%) 1 0/80 (0%) 0
    Interstitial lung disease 1/82 (1.2%) 1 0/80 (0%) 0
    Pleural effusion 1/82 (1.2%) 1 3/80 (3.8%) 3
    Pneumonia aspiration 2/82 (2.4%) 3 1/80 (1.3%) 1
    Pneumothorax 1/82 (1.2%) 1 0/80 (0%) 0
    Pulmonary embolism 2/82 (2.4%) 2 0/80 (0%) 0
    Vascular disorders
    Deep vein thrombosis 5/82 (6.1%) 5 1/80 (1.3%) 1
    Embolism venous 0/82 (0%) 0 1/80 (1.3%) 1
    Hypertension 1/82 (1.2%) 1 0/80 (0%) 0
    Hypotension 1/82 (1.2%) 1 3/80 (3.8%) 3
    Superior vena cava syndrome 0/82 (0%) 0 1/80 (1.3%) 1
    Thrombosis 0/82 (0%) 0 1/80 (1.3%) 1
    Other (Not Including Serious) Adverse Events
    Ramucirumab and mFOLFOX6 Placebo and mFOLFOX6
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 82/82 (100%) 79/80 (98.8%)
    Blood and lymphatic system disorders
    Anaemia 29/82 (35.4%) 41 38/80 (47.5%) 58
    Leukopenia 7/82 (8.5%) 18 9/80 (11.3%) 14
    Neutropenia 29/82 (35.4%) 76 33/80 (41.3%) 108
    Thrombocytopenia 30/82 (36.6%) 62 20/80 (25%) 45
    Eye disorders
    Vision blurred 3/82 (3.7%) 3 6/80 (7.5%) 7
    Gastrointestinal disorders
    Abdominal distension 8/82 (9.8%) 9 5/80 (6.3%) 5
    Abdominal pain 17/82 (20.7%) 20 14/80 (17.5%) 20
    Abdominal pain upper 8/82 (9.8%) 10 8/80 (10%) 11
    Ascites 5/82 (6.1%) 8 2/80 (2.5%) 2
    Constipation 36/82 (43.9%) 41 32/80 (40%) 41
    Diarrhoea 36/82 (43.9%) 67 33/80 (41.3%) 56
    Dry mouth 6/82 (7.3%) 6 4/80 (5%) 5
    Dyspepsia 7/82 (8.5%) 9 8/80 (10%) 8
    Dysphagia 10/82 (12.2%) 15 13/80 (16.3%) 18
    Flatulence 3/82 (3.7%) 3 5/80 (6.3%) 5
    Gastrooesophageal reflux disease 6/82 (7.3%) 9 5/80 (6.3%) 11
    Nausea 52/82 (63.4%) 72 56/80 (70%) 82
    Oral pain 5/82 (6.1%) 6 4/80 (5%) 4
    Stomatitis 10/82 (12.2%) 16 16/80 (20%) 21
    Vomiting 32/82 (39%) 49 28/80 (35%) 42
    General disorders
    Asthenia 12/82 (14.6%) 13 8/80 (10%) 13
    Chest pain 2/82 (2.4%) 2 7/80 (8.8%) 11
    Chills 5/82 (6.1%) 5 2/80 (2.5%) 2
    Fatigue 57/82 (69.5%) 91 56/80 (70%) 81
    Mucosal inflammation 17/82 (20.7%) 23 9/80 (11.3%) 13
    Oedema peripheral 20/82 (24.4%) 30 14/80 (17.5%) 19
    Pyrexia 9/82 (11%) 12 11/80 (13.8%) 11
    Temperature intolerance 8/82 (9.8%) 8 14/80 (17.5%) 17
    Infections and infestations
    Upper respiratory tract infection 6/82 (7.3%) 6 5/80 (6.3%) 6
    Urinary tract infection 11/82 (13.4%) 11 9/80 (11.3%) 12
    Injury, poisoning and procedural complications
    Contusion 3/82 (3.7%) 3 5/80 (6.3%) 5
    Infusion related reaction 7/82 (8.5%) 14 5/80 (6.3%) 7
    Investigations
    Alanine aminotransferase increased 5/82 (6.1%) 6 7/80 (8.8%) 9
    Aspartate aminotransferase increased 7/82 (8.5%) 10 11/80 (13.8%) 18
    Blood alkaline phosphatase increased 6/82 (7.3%) 7 15/80 (18.8%) 24
    Blood creatinine increased 5/82 (6.1%) 11 1/80 (1.3%) 1
    Neutrophil count decreased 16/82 (19.5%) 50 9/80 (11.3%) 16
    Platelet count decreased 19/82 (23.2%) 45 12/80 (15%) 24
    Weight decreased 28/82 (34.1%) 41 21/80 (26.3%) 31
    White blood cell count decreased 5/82 (6.1%) 8 6/80 (7.5%) 8
    Metabolism and nutrition disorders
    Decreased appetite 37/82 (45.1%) 47 22/80 (27.5%) 36
    Dehydration 21/82 (25.6%) 28 12/80 (15%) 14
    Hyperglycaemia 9/82 (11%) 15 10/80 (12.5%) 22
    Hypoalbuminaemia 5/82 (6.1%) 7 4/80 (5%) 8
    Hypocalcaemia 9/82 (11%) 15 4/80 (5%) 9
    Hypokalaemia 16/82 (19.5%) 23 8/80 (10%) 13
    Hypomagnesaemia 3/82 (3.7%) 3 5/80 (6.3%) 5
    Hyponatraemia 3/82 (3.7%) 7 6/80 (7.5%) 8
    Hypophosphataemia 6/82 (7.3%) 13 1/80 (1.3%) 4
    Musculoskeletal and connective tissue disorders
    Arthralgia 2/82 (2.4%) 4 8/80 (10%) 9
    Back pain 10/82 (12.2%) 12 11/80 (13.8%) 19
    Bone pain 7/82 (8.5%) 7 7/80 (8.8%) 7
    Muscular weakness 8/82 (9.8%) 14 5/80 (6.3%) 5
    Myalgia 1/82 (1.2%) 1 6/80 (7.5%) 8
    Pain in extremity 9/82 (11%) 9 7/80 (8.8%) 9
    Pain in jaw 6/82 (7.3%) 6 2/80 (2.5%) 2
    Nervous system disorders
    Dizziness 19/82 (23.2%) 22 12/80 (15%) 15
    Dysgeusia 13/82 (15.9%) 14 14/80 (17.5%) 15
    Headache 18/82 (22%) 24 12/80 (15%) 16
    Memory impairment 5/82 (6.1%) 5 0/80 (0%) 0
    Paraesthesia 8/82 (9.8%) 10 20/80 (25%) 33
    Peripheral motor neuropathy 3/82 (3.7%) 3 6/80 (7.5%) 8
    Peripheral sensory neuropathy 44/82 (53.7%) 68 43/80 (53.8%) 73
    Psychiatric disorders
    Anxiety 4/82 (4.9%) 4 8/80 (10%) 8
    Depression 7/82 (8.5%) 7 4/80 (5%) 5
    Insomnia 15/82 (18.3%) 15 20/80 (25%) 24
    Renal and urinary disorders
    Dysuria 0/82 (0%) 0 5/80 (6.3%) 5
    Respiratory, thoracic and mediastinal disorders
    Cough 19/82 (23.2%) 21 15/80 (18.8%) 18
    Dysphonia 8/82 (9.8%) 8 1/80 (1.3%) 2
    Dyspnoea 16/82 (19.5%) 23 16/80 (20%) 24
    Epistaxis 24/82 (29.3%) 28 9/80 (11.3%) 9
    Hiccups 2/82 (2.4%) 2 6/80 (7.5%) 7
    Nasal congestion 5/82 (6.1%) 5 2/80 (2.5%) 2
    Skin and subcutaneous tissue disorders
    Alopecia 9/82 (11%) 10 8/80 (10%) 10
    Dry skin 3/82 (3.7%) 3 9/80 (11.3%) 9
    Pruritus 3/82 (3.7%) 6 6/80 (7.5%) 8
    Rash 4/82 (4.9%) 4 5/80 (6.3%) 6
    Vascular disorders
    Hypertension 30/82 (36.6%) 41 10/80 (12.5%) 10
    Hypotension 7/82 (8.5%) 10 7/80 (8.8%) 14

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    Investigators agreed to delay independently publishing or disclosing data, findings or conclusions from the study except as part of a multi-center publication. Upon study publication or if the draft publication is not produced within approximately 6 months of the final report of the study results, investigators may independently publish, subject to confidential information review/redaction by sponsor. The sponsor may request publication delay up to 90 days to seek patent protection.

    Results Point of Contact

    Name/Title Chief Medical Officer
    Organization Eli Lilly and Company
    Phone 800-545-5979
    Email
    Responsible Party:
    Eli Lilly and Company
    ClinicalTrials.gov Identifier:
    NCT01246960
    Other Study ID Numbers:
    • 14057
    • I4T-MC-JVBT
    First Posted:
    Nov 24, 2010
    Last Update Posted:
    Oct 8, 2014
    Last Verified:
    Oct 1, 2014