Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study of Ramucirumab and Best Supportive Care (BSC) Versus Placebo and BSC as Second-Line Treatment in Patients With Hepatocellular Carcinoma and Elevated Baseline Alpha-Fetoprotein (AFP) Following First-Line Therapy With Sorafenib
- Conditions
- Hepatocellular Carcinoma
- Registration Number
- JPRN-jRCT2080222919
- Lead Sponsor
- Eli Lilly Japan K.K.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- completed
- Sex
- All
- Target Recruitment
- Not specified
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 more than or equal14 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.
-More than or equal1 measurable lesion per Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 that has not been previously treated with locoregional therapy.
-Child-Pugh score less than 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 more than or equal 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 less than or equal 1.5 times upper limit of normal value (ULN), aspartate transaminase (AST) and alanine transaminase (ALT) less than or equal 5 times ULN.
-Creatinine clearance more than or equal 60 milliliters/minute.
-Urinary protein is less than or equal 1+ on dipstick or routine urinalysis or 24-hour urine demonstrating less than 1 gram of protein.
-Absolute neutrophil count more than or equal 1.0 x 10^9/Liter, hemoglobin more than or equal 9 grams/deciliter, and platelets more than or equal 75 x 10^9/Liter.
-International Normalized Ratio (INR) less than or equal 1.5 and a partial thromboplastin time (PTT) less than or equal 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.
-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 less than or equal 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, less than 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:
a. Human immunodeficiency virus infection or acquired immunodeficiency syndrome-related illness.
b. Active or uncontrolled clinically serious infection. (Participants with chronic viral hepatitis are eligible.)
c. Ongoing or recent history of drug abuse.
d. 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.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method