A Study of Ramucirumab in Participants With Gastric, Esophageal, and Gastroesophageal Cancer
Condition: Stomach Cancer; Esophageal Cancer
MeSH terms: Stomach Neoplasms
Intervention: Ramucirumab; Placebo; Oxaliplatin; Leucovorin; 5-Fluorouracil
Intervention description: Administered intravenously; Administered intravenously; Administered intravenously; Administered intravenously; Administered intravenously
Intervention MeSH terms: Leucovorin; Fluorouracil; Oxaliplatin; Ramucirumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 168.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: cancer; stomach; esophagus; gastroesophageal

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.
    

Eligibility criteria:

        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