Patient case: 68-year-old male with non-small cell carcinoma; genetic feature: MET

Clinical trial: A Study of Ramucirumab (LY3009806) Versus Placebo in Participants With Hepatocellular Carcinoma and Elevated Baseline Alpha-Fetoprotein

Summary: The purpose of this study is to evaluate the safety and efficacy of ramucirumab in participants with hepatocellular carcinoma (HCC) and elevated baseline alpha-fetoprotein. Participants will be randomized to ramucirumab or placebo in a 2:1 ratio.


Eligibility: Inclusion Criteria:
  -  A diagnosis of HCC based on histopathologic findings, or a diagnosis of cirrhosis and a tumor with classical HCC imaging characteristics.
  -  Prior sorafenib treatment for at least 14 days and discontinuation of sorafenib ≥14 days prior to randomization.
  -  Radiographic disease progression during or after sorafenib therapy or discontinuation of sorafenib because of intolerance.
  -  Sorafenib was the only systemic therapy for HCC.
  -  ≥1 measurable lesion per Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 that has not been previously treated with locoregional therapy. A participant with a lesion(s) that has previously been treated with locoregional therapy is also eligible, if the lesion has documented progression after locoregional treatment and is measureable.
  -  Child-Pugh score <7 (Child-Pugh Class A).
  -  Barcelona Clinic Liver Cancer (BCLC) Stage C disease or BCLC Stage B disease not amenable to locoregional therapy or refractory to locoregional therapy.
  -  Baseline AFP ≥400 nanograms/milliliter.
  -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  -  Resolution of all clinically significant toxic effects of prior therapy.
  -  Total bilirubin ≤1.5 times upper limit of normal value (ULN), aspartate transaminase (AST) and alanine transaminase (ALT) ≤5 × ULN.
  -  Creatinine clearance ≥60 milliliters/minute.
  -  Urinary protein is ≤1+ on dipstick or routine urinalysis or 24-hour urine demonstrating <1 gram of protein.
  -  Absolute neutrophil count ≥1.0 × 10^9/Liter, hemoglobin ≥9 grams/deciliter, and platelets ≥75 × 10^9/Liter.
  -  International Normalized Ratio (INR) ≤1.5 and a partial thromboplastin time (PTT) ≤5 seconds above the ULN.
  -  Surgically sterile, postmenopausal, or compliant with a highly effective contraceptive method.
  -  If a woman of childbearing potential, a negative serum pregnancy test prior to randomization.
  -  Willing to provide blood for research.
  Exclusion Criteria:
  -  Fibrolamellar carcinoma or mixed hepatocellular cholangiocarcinoma.
  -  Concurrent malignancy. Participants with carcinoma in situ of any origin and participants with prior malignancies in remission may be eligible with sponsor approval.
  -  Previous brain metastases, leptomeningeal disease, or uncontrolled spinal cord compression.
  -  History of or current hepatic encephalopathy or clinically meaningful ascites.
  -  Ongoing or recent hepatorenal syndrome.
  -  Liver transplant.
  -  Previous systemic therapy with vascular endothelial growth factor (VEGF) pathway inhibitors other than sorafenib for treatment of HCC.
  -  Hepatic locoregional therapy following sorafenib or within 28 days prior to randomization.
  -  Major surgical procedure, traumatic injury, non-healing wound, or peptic ulcer ≤28 days prior to randomization.
  -  Placement of a subcutaneous venous access device within 7 days prior to the first dose of study treatment unless the procedure is judged of low risk of bleeding.
  -  Enrolled in a clinical trial involving an investigational product or nonapproved use of a drug or in medical research judged not to be scientifically or medically compatible with this study.
  -  Discontinued from study treatment from another clinical trial within 28 days prior to randomization.
  -  Known allergy to any of the treatment components.
  -  Uncontrolled hypertension.
  -  Any arterial thrombotic event, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack, <6 months prior to randomization.
  -  Any bleeding episode considered life-threatening, or any Grade 3 or 4 gastrointestinal bleeding episode in the 3 months prior to randomization requiring intervention.
  -  Esophageal or gastric varices that require intervention or represent high bleeding risk. Participants with evidence of portal hypertension or prior bleeding must have had endoscopic evaluation within 3 months prior to randomization.
  -  Gastrointestinal perforation or fistulae within 6 months prior to randomization.
  -  Symptomatic congestive heart failure (New York Heart Association II-IV), unstable angina pectoris, or symptomatic or poorly controlled cardiac arrhythmia.
  -  Pregnant or breast-feeding.
  -  Any medical or psychiatric condition that may increase the risk associated with study participation or may interfere with the interpretation of study results. Conditions include but are not limited to:
  -  Human immunodeficiency virus infection or acquired immunodeficiency syndrome-related illness.
  -  Active or uncontrolled clinically serious infection. (Participants with chronic viral hepatitis are eligible.)
  -  Ongoing or recent history of drug abuse.
  -  Uncontrolled hereditary or acquired thrombotic or bleeding disorder.
  -  Bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection.
  -  Therapeutic dose anticoagulation with warfarin, low molecular-weight heparin, or similar agents.
  -  Chronic therapy with nonsteroidal anti-inflammatory agents or other anti-platelet agents. Aspirin at doses up to 100 milligrams/day is permitted.

Relevance to patient case: not relevant