A Study of Ramucirumab (LY3009806) in Participants With Advanced Liver Cancer
Condition: Carcinoma, Hepatocellular
MeSH terms: Carcinoma; Carcinoma, Hepatocellular
Intervention: Ramucirumab; FOLFOX4
Intervention description: Administered IV.; Administered IV.
Intervention MeSH terms: Leucovorin; Fluorouracil; Oxaliplatin; Ramucirumab
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 8.0
Sex: All
Minimum age: 20 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      The main purpose of this study is to determine if the advised dose of ramucirumab is safe to
      be taken with chemotherapy treatment in participants with advanced liver tumors.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histological or cytological diagnosis of hepatocellular carcinoma (HCC) or imaging
             findings consistent with HCC in a participant with liver cirrhosis and
             alpha-fetoprotein > 200 nanogram per milliliter

          -  At least 1 measurable or non-measurable lesion

          -  Child-Pugh A

          -  Barcelona Clinic Liver Cancer (BCLC) stage C or BCLC stage B not amenable to
             locoregional therapy or refractory to locoregional therapy

          -  Eastern Cooperative Oncology Group Performance Status of 0 or 1

          -  Have not received previous systemic therapy for advanced HCC

          -  Have resolution to Grade ≤1 of all clinically significant toxic effects of prior
             locoregional therapy

          -  Adequate organ function including: Absolute neutrophil coun t≥1.5×109/liter (L),
             hemoglobin ≥9 gram/deciliter, and platelets ≥90×109/L; Total bilirubin level ≤1.5 the
             upper limit of the normal range (ULN), aspartate transaminase and alanine transaminase
             ≤5 ULN, albumin >28 gram/L; Serum creatinine level ≤1.5 ULN; or calculated serum
             creatinine clearance ≥50 milliliter/minute; International Normalized Ratio≤1.5 and
             partial thromboplastin time ≤5 seconds above ULN

          -  The urinary protein is ≤ 1+. If ≥ 2+ proteinuria, the 24-hour urine protein is <1000
             milligram

          -  An estimated life expectancy of at least 12 weeks

        Exclusion Criteria:

          -  Received any investigational therapy or non-approved drug within 28 days prior to
             enrollment

          -  Undergone major surgery within 28 days prior to enrollment, or undergone central
             venous access device placement within 7 days prior to enrollment

          -  Undergone hepatic locoregional therapy within 28 days prior to enrollment

          -  Undergone radiation to any nonhepatic site within 14 days prior to enrollment

          -  Prior liver transplant

          -  Fibrolamellar carcinoma or cholangiocellular carcinoma

          -  Received any transfusion, blood component preparation, erythropoietin, albumin
             preparation, or granulocyte-colony stimulating factors within 14 days prior to
             enrollment

          -  Receiving therapeutic anticoagulation with warfarin, low-molecular weight heparin, or
             similar agents

          -  Receiving ongoing therapy with nonsteroidal anti-inflammatory agents or other
             antiplatelet agents.

          -  Known human immunodeficiency virus infection or acquired immunodeficiency
             syndrome-related illness

          -  Active or uncontrolled clinically serious infection

          -  Uncontrolled thrombotic or hemorrhagic disorder

          -  Serious or nonhealing wound, ulcer, or bone fracture within 28 days prior to
             enrollment

          -  History of gastrointestinal perforation or obstruction

          -  History of or current hepatic encephalopathy or current clinically meaningful ascites

          -  Known allergy to monoclonal antibody, fluorouracil, oxaliplatin or their excipients

          -  Interstitial pneumonia or interstitial fibrosis of the lung

          -  Central nervous system metastases or carcinomatous meningitis

          -  Known history of dihydropyrimidine dehydrogenase deficiency

          -  Symptomatic congestive heart failure, unstable angina pectoris, or symptomatic or
             poorly controlled cardiac arrhythmia

          -  Experienced any arterial thromboembolic event

          -  Uncontrolled arterial hypertension

          -  Grade 3-4 venous thromboembolic events occurring within 3 months prior to enrollment

          -  Experienced any grade 3-4 gastrointestinal bleeding or any variceal bleeding episode
             in the 3 months prior to enrollment requiring transfusion, endoscopic or operative
             intervention

          -  Esophageal or gastric varices that require immediate intervention or represent a high
             bleeding risk

          -  Pre-existing grade ≥ 2 motor or sensory neuropathy