Back to results

A Study of Ramucirumab (LY3009806) Versus Placebo in Participants With Hepatocellular Carcinoma and Elevated Baseline Alpha-Fetoprotein (REACH-2)

Primary Purpose

Hepatocellular Carcinoma

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Ramucirumab

Placebo

About this trial

This is an interventional treatment trial for Hepatocellular Carcinoma focused on measuring liver cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

A diagnosis of HCC based on histopathologic findings, or a diagnosis of cirrhosis and a tumor with classical HCC imaging characteristics.
Sorafenib was the only systemic therapy for HCC and was discontinued for disease progression or intolerance (Main Global and ME2 Cohorts only).
The participant received ≤2 prior systemic therapy regimen, excluding prior sorafenib or chemotherapy, for the treatment of HCC (OLE Cohort only).
≥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. The participant has provided signed informed consent prior to any study specific procedures and is amenable to compliance with protocol schedules and testing.

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 (Main Global and ME2 cohorts only; Participants with prior liver transplant may be eligible for OLE cohort).
Hepatic locoregional therapy following prior systemic therapy or within 28 days prior to randomization.
Major surgical procedure, traumatic injury, non-healing wound, or peptic ulcer ≤28 days prior to randomization.
Received radiation to any nonhepatic (for example, bone) site within 14 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 unapproved 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.
The participant received prior immunotherapy and is experiencing or has experienced any of the following (OLE cohort only):
- Any clinically significant Grade ≥3 immune-related adverse event (irAE)
- Any grade neurologic or ocular irAE
- Any grade immune-related pneumonitis, cardiomyopathy, or hepatitis
The participant received prior immunotherapy and at the time of study enrollment, requires steroids or other immunosuppressive agents (OLE cohort only).

Sites / Locations

Pacific Hematology and Oncology Associates
UCLA Medical Center
Georgetown University Medical Center
University of Iowa Hospital
Massachusetts General Hospital
Mount Sinai Medical Center
University of Oklahoma Health Sciences Center
OREGON HEALTH and SCIENCE UNIVERSITY
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.
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.
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.
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.
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.
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.
Fundação PIO XII
"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."
Cenantron - Centro Avançado de Tratamento Oncológico
Associação Hospital de Caridade Ijuí
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.
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.
For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.
"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."
"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."
"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."
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.
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.
"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."
"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."
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.
"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."
"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."
"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."
"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."
"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."
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.
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.
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.
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.
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.
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.
"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."
"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."
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.
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
"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."
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.
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.
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.
"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."
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
"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."
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
"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."
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.
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
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.
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.
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.
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.
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.
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.
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.
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.
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.
"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."
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.
"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."
"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."
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
"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."
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.
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
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
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.
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.
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.
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.
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.
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.
Hospital Universitari de Girona Dr. Josep Trueta
Hospital Clínico San Carlos
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.
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.
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.
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.
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.
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.
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.
"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."
"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."
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.
For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.
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.
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.
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.
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.
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.
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.
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.
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.

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Arm Label

Ramucirumab + Best Supportive Care (BSC)

Placebo + BSC

Open Label Ramucirumab + BSC

Ramucirumab MEE Cohort + BSC

Placebo MEE Cohort + BSC

Arm Description

8 milligrams per kilogram (mg/kg) ramucirumab administered as an intravenous (IV) injection on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.

Placebo administered IV on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.

8 mg/kg ramucirumab administered IV on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.

Placebo administered IV on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.

Outcomes

Primary Outcome Measures

Overall Survival (OS)

OS time was measured from date of randomization to date of death from any cause. Participants who were not known to have died on or before the date of data cut-off, OS data was censored on the last date (on or before the cut-off date) the participant was known to be alive.

Secondary Outcome Measures

Progression Free Survival (PFS)

Progression-free survival is defined as time from the date of randomization to the date of first observation of objective progression or death from any cause.

Time to Radiographic Progression

Time to radiographic progression is defined as the time from the date of randomization to the date of first observation of objective progression.

Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR): Objective Response Rate (ORR)

Objective response rate is defined as the percentage of participants who achieve a best overall response of complete response (CR) + partial response (PR). ORR = CR + PR. CR is the disappearance of all non-target lesions and normalisation of tumour marker level. All lymph nodes must be non-pathological in size (<10 mm short axis). PR is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Tumor marker results must have normalized. Best overall response is classified based on the overall responses assessed by study investigators according to Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1.

Pharmacokinetics (PK): Minimum Serum Concentration (Cmin) Before 2nd, 4th, 7th, and 10th Infusion

PK Cmin of Ramucirumab Blood samples were collected at specified time points, and in the event of an infusion-related reaction, for assessment of ramucirumab serum concentrations.

PK: Serum Concentration Maximum (Cmax) After 1st, 2nd, 4th, 7th and 10th Ram Infusion

PK Cmax of Ramucirumab Blood samples were collected at specified time points, and in the event of an infusion-related reaction, for assessment of ramucirumab serum concentrations.

Percentage of Participants With Anti-Ramucirumab Antibodies

Percentage of participants with positive treatment emergent anti-drug antibodies was summarized by treatment group. A treatment-emergent ADA (TEADA) was defined as: having a negative ADA at baseline and an ADA titer greater than or equal to 1:20 (that is (i.e.), greater than 2-fold from the minimal required dilution of 1:10) any time post baseline (i.e., treatment-induced); or a 4-fold or greater change in ADA titer from baseline for participants that had a detectable ADA titer at baseline (i.e., treatment boosted).

Time to Deterioration of Functional Assessment of Cancer Therapy (FACT) Hepatobiliary Symptom Index-8 (FHSI-8)

The FACT Hepatobiliary Symptom Index (FHSI-8) is a instrument with specific focus regarding the most frequent and concerning symptoms experienced by participants with hepatobiliary malignancies, including lack of energy, nausea, pain, weight loss, pain in back, fatigue, jaundice, stomach pain or discomfort. The (FHSI-8) questionnaire was used to assess the time to deterioration of FSHI-8 total score issued from the date of randomization to the first date observing deterioration, with the deterioration threshold defined as a decrease ≥ 3-points from baseline. In case of no deterioration, the participants were censored at the time of the last FSHI-8 item recording. FHSI-8 total score ranges from 0 to 32 where "0" is a severely symptomatic participant and the highest score indicates an asymptomatic participant. Kaplan-Meier method Hazard ratio was used to estimate (Ramucirumab versus Placebo) and 95% Confidence Interval (CI) (Wald) were estimated from un-stratified/stratified Cox model.

Change From Baseline in EuroQol 5-Dimension 5-Level (EQ-5D-5L) Questionnaire

The EQ-5D-5L is a nonspecific and standardized instrument for use as a measure of self-reported health status (EuroQol Group 1990; Herdman et al. 2011). Participants completed the 5-level (no problems, slight problems, moderate problems, severe problems, and extreme problems), 5-dimension (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) questionnaire concerning their current health state. A unique EQ-5D-5L health state scale ranges from 0 to 100 and is defined by combining 1 level from each of the 5 dimensions. Participants indicated their current health status by marking on a continuum ranging from 100 (best imaginable health state) to 0 (worst imaginable health state).

Time to Deterioration in Eastern Cooperative Oncology Group Performance Status (ECOG PS)

Time to deterioration in ECOG PS is defined as the time from the date of randomization to the first date observing ECOG PS 2 (ie, deterioration from baseline status of 0 [fully active] or 1 [restricted in physically strenuous activity but ambulatory and able to carry out light work]). Participants without PS deterioration were censored at their last documented assessments of 0 or 1. Assessments included ECOG Performance Status (PS): 2- Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours, 3 -Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours, 4 -Completely disabled, cannot carry on any self-care. Totally confined to bed or chair, 5- Dead.

Full Information

NCT ID

NCT02435433

First Posted

May 1, 2015

Last Updated

December 22, 2022

Sponsor

Eli Lilly and Company

1. Study Identification

Unique Protocol Identification Number

NCT02435433

Brief Title

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

Acronym

REACH-2

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

December 1, 2022

Overall Recruitment Status

Completed

Study Start Date

July 20, 2015 (Actual)

Primary Completion Date

March 15, 2018 (Actual)

Study Completion Date

November 19, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Eli Lilly and Company

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief 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 (Main Global Cohort and China Maximized Extended Enrollment [MEE] Cohort). Participants may also receive ramucirumab if eligible to be enrolled in Open-Label Expansion (OLE) Cohort.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hepatocellular Carcinoma

Keywords

liver cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

399 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Ramucirumab + Best Supportive Care (BSC)

Arm Type

Experimental

Arm Description

8 milligrams per kilogram (mg/kg) ramucirumab administered as an intravenous (IV) injection on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.

Arm Title

Placebo + BSC

Arm Type

Placebo Comparator

Arm Description

Placebo administered IV on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.

Arm Title

Open Label Ramucirumab + BSC

Arm Type

Experimental

Arm Description

8 mg/kg ramucirumab administered IV on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.

Arm Title

Ramucirumab MEE Cohort + BSC

Arm Type

Experimental

Arm Description

8 mg/kg ramucirumab administered IV on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.

Arm Title

Placebo MEE Cohort + BSC

Arm Type

Placebo Comparator

Arm Description

Placebo administered IV on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.

Intervention Type

Drug

Intervention Name(s)

Ramucirumab

Other Intervention Name(s)

Cyramza, LY3009806

Intervention Description

Administered IV

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Administered IV

Primary Outcome Measure Information:

Title

Overall Survival (OS)

Description

Time Frame

From Date of Randomization to Death from Any Cause (Up to 28 Months)

Secondary Outcome Measure Information:

Title

Progression Free Survival (PFS)

Description

Progression-free survival is defined as time from the date of randomization to the date of first observation of objective progression or death from any cause.

Time Frame

From Randomization to Objective Progression or Death from Any Cause (Up to 28 Months)

Title

Time to Radiographic Progression

Description

Time to radiographic progression is defined as the time from the date of randomization to the date of first observation of objective progression.

Time Frame

From Randomization to Objective Progression (Up to 28 Months)

Title

Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR): Objective Response Rate (ORR)

Description

Time Frame

From Randomization to Objective Progression (Up to 28 Months)

Title

Pharmacokinetics (PK): Minimum Serum Concentration (Cmin) Before 2nd, 4th, 7th, and 10th Infusion

Description

PK Cmin of Ramucirumab Blood samples were collected at specified time points, and in the event of an infusion-related reaction, for assessment of ramucirumab serum concentrations.

Time Frame

Predose, Weeks 2, 6, 12 and 18, Day 1; Up to 3 Days Before Infusion (14-Day Cycles)

Title

PK: Serum Concentration Maximum (Cmax) After 1st, 2nd, 4th, 7th and 10th Ram Infusion

Description

PK Cmax of Ramucirumab Blood samples were collected at specified time points, and in the event of an infusion-related reaction, for assessment of ramucirumab serum concentrations.

Time Frame

Weeks 0, 2, 6, 12 and 18, Day 1; 1 hour to 1.5 hours Post End of Infusion (14 day-Cycles)

Title

Percentage of Participants With Anti-Ramucirumab Antibodies

Description

Time Frame

Predose Cycle 1: 7 Days prior to First Infusion, Cycle 4: 3 Days Prior to Infusion, Cycle 7 through Follow Up (Up to 28 Months)

Title

Time to Deterioration of Functional Assessment of Cancer Therapy (FACT) Hepatobiliary Symptom Index-8 (FHSI-8)

Description

Time Frame

From Randomization to the First Date of Deterioration Observation (≥ 3-point decrease) (Up to 28 Months)

Title

Change From Baseline in EuroQol 5-Dimension 5-Level (EQ-5D-5L) Questionnaire

Description

Time Frame

From Randomization through End of Study (Up to 28 Months)

Title

Time to Deterioration in Eastern Cooperative Oncology Group Performance Status (ECOG PS)

Description

Time Frame

From Randomization through First Date of Deterioration Observation (ECOG PS≥2) (Up to 28 Months)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: A diagnosis of HCC based on histopathologic findings, or a diagnosis of cirrhosis and a tumor with classical HCC imaging characteristics. Sorafenib was the only systemic therapy for HCC and was discontinued for disease progression or intolerance (Main Global and MEE Cohorts only). The participant received ≤2 prior systemic therapy regimen, excluding prior sorafenib or chemotherapy, for the treatment of HCC (OLE Cohort only). ≥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. The participant has provided signed informed consent prior to any study specific procedures and is amenable to compliance with protocol schedules and testing. 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 (Main Global and MEE cohorts only; Participants with prior liver transplant may be eligible for OLE cohort). Hepatic locoregional therapy following prior systemic therapy or within 28 days prior to randomization. Major surgical procedure, traumatic injury, non-healing wound, or peptic ulcer ≤28 days prior to randomization. Received radiation to any nonhepatic (for example, bone) site within 14 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 unapproved 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. The participant received prior immunotherapy and is experiencing or has experienced any of the following (OLE cohort only): Any clinically significant Grade ≥3 immune-related adverse event (irAE) Any grade neurologic or ocular irAE Any grade immune-related pneumonitis, cardiomyopathy, or hepatitis The participant received prior immunotherapy and at the time of study enrollment, requires steroids or other immunosuppressive agents (OLE cohort only).

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

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)

Organizational Affiliation

Eli Lilly and Company

Official's Role

Study Director

Facility Information:

Facility Name

Pacific Hematology and Oncology Associates

City

Daly City

State/Province

California

ZIP/Postal Code

94115

Country

United States

Facility Name

UCLA Medical Center

City

Los Angeles

State/Province

California

ZIP/Postal Code

90024

Country

United States

Facility Name

Georgetown University Medical Center

City

Washington

State/Province

District of Columbia

ZIP/Postal Code

20007

Country

United States

Facility Name

University of Iowa Hospital

City

Iowa City

State/Province

Iowa

ZIP/Postal Code

52242

Country

United States

Facility Name

Massachusetts General Hospital

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02114

Country

United States

Facility Name

Mount Sinai Medical Center

City

New York

State/Province

New York

ZIP/Postal Code

10029

Country

United States

Facility Name

University of Oklahoma Health Sciences Center

City

Oklahoma City

State/Province

Oklahoma

ZIP/Postal Code

73104

Country

United States

Facility Name

OREGON HEALTH and SCIENCE UNIVERSITY

City

Portland

State/Province

Oregon

ZIP/Postal Code

97239

Country

United States

Facility Name

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.

City

Kurralta Park

ZIP/Postal Code

5037

Country

Australia

Facility Name

City

Woodville

ZIP/Postal Code

5011

Country

Australia

Facility Name

City

Linz

ZIP/Postal Code

4020

Country

Austria

Facility Name

City

Wien

ZIP/Postal Code

1090

Country

Austria

Facility Name

City

Brussels

ZIP/Postal Code

1200

Country

Belgium

Facility Name

City

Liege

ZIP/Postal Code

4000

Country

Belgium

Facility Name

Fundação PIO XII

City

Barretos

ZIP/Postal Code

14784-400

Country

Brazil

Facility Name

"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."

City

Barretos

ZIP/Postal Code

14784700

Country

Brazil

Facility Name

Cenantron - Centro Avançado de Tratamento Oncológico

City

Belo Horizonte

ZIP/Postal Code

30130-090

Country

Brazil

Facility Name

Associação Hospital de Caridade Ijuí

City

Ijui

ZIP/Postal Code

98700 000

Country

Brazil

Facility Name

City

Porto Alegre

ZIP/Postal Code

90470-340

Country

Brazil

Facility Name

City

São Paulo

ZIP/Postal Code

04039-901

Country

Brazil

Facility Name

For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.

City

Montreal

ZIP/Postal Code

H2X 3E4

Country

Canada

Facility Name

City

Toronto

ZIP/Postal Code

M5G 2M9

Country

Canada

Facility Name

City

Beijing

ZIP/Postal Code

100032

Country

China

Facility Name

City

Beijing

ZIP/Postal Code

100142

Country

China

Facility Name

City

Beijing

Country

China

Facility Name

City

Beijing

Country

China

Facility Name

City

Changsha

ZIP/Postal Code

410011

Country

China

Facility Name

City

Changsha

ZIP/Postal Code

410013

Country

China

Facility Name

City

Chongqing

ZIP/Postal Code

400038

Country

China

Facility Name

City

Guangdong

ZIP/Postal Code

510515

Country

China

Facility Name

City

Guangzhou

ZIP/Postal Code

510080

Country

China

Facility Name

City

Hangzhou

ZIP/Postal Code

310003

Country

China

Facility Name

City

Hangzhou

ZIP/Postal Code

310009

Country

China

Facility Name

City

Hangzhou

ZIP/Postal Code

310022

Country

China

Facility Name

City

Hebei

ZIP/Postal Code

050011

Country

China

Facility Name

City

Hefei

ZIP/Postal Code

230022

Country

China

Facility Name

City

Heilongjiang

ZIP/Postal Code

150081

Country

China

Facility Name

City

Henan

ZIP/Postal Code

450008

Country

China

Facility Name

City

Hubei

ZIP/Postal Code

56456

Country

China

Facility Name

City

Nanjing

ZIP/Postal Code

210002

Country

China

Facility Name

City

Nanjing

ZIP/Postal Code

210006

Country

China

Facility Name

City

Nanning

ZIP/Postal Code

530021

Country

China

Facility Name

City

Qingdao

ZIP/Postal Code

266003

Country

China

Facility Name

City

Shanghai

ZIP/Postal Code

200030

Country

China

Facility Name

City

Shanghai

ZIP/Postal Code

200127

Country

China

Facility Name

City

Shanghai

Country

China

Facility Name

City

Shanghai

Country

China

Facility Name

City

Shenyang

ZIP/Postal Code

100042

Country

China

Facility Name

City

Wu Han

ZIP/Postal Code

430030

Country

China

Facility Name

City

Xi'an

ZIP/Postal Code

710032

Country

China

Facility Name

City

Brno

ZIP/Postal Code

656 53

Country

Czechia

Facility Name

City

Praha 5

ZIP/Postal Code

150 06

Country

Czechia

Facility Name

City

Amiens

ZIP/Postal Code

80054

Country

France

Facility Name

City

Avignon

ZIP/Postal Code

84918

Country

France

Facility Name

City

Besancon

ZIP/Postal Code

25030

Country

France

Facility Name

City

Caen

ZIP/Postal Code

14033

Country

France

Facility Name

City

Clermont-Ferrand

ZIP/Postal Code

63003

Country

France

Facility Name

City

Lyon

ZIP/Postal Code

69317

Country

France

Facility Name

City

Montpellier

ZIP/Postal Code

34295

Country

France

Facility Name

City

Nantes

ZIP/Postal Code

44093

Country

France

Facility Name

City

Pessac

ZIP/Postal Code

33604

Country

France

Facility Name

City

Rennes

ZIP/Postal Code

35042

Country

France

Facility Name

City

Saint Etienne

ZIP/Postal Code

42000

Country

France

Facility Name

City

Bayern

ZIP/Postal Code

81377

Country

Germany

Facility Name

City

Berlin

ZIP/Postal Code

13125

Country

Germany

Facility Name

City

Essen

ZIP/Postal Code

45122

Country

Germany

Facility Name

City

Frankfurt

ZIP/Postal Code

60590

Country

Germany

Facility Name

City

Hamburg

ZIP/Postal Code

20246

Country

Germany

Facility Name

City

Hannover

ZIP/Postal Code

30625

Country

Germany

Facility Name

City

Leipzig

ZIP/Postal Code

04103

Country

Germany

Facility Name

City

Magdeburg

ZIP/Postal Code

39120

Country

Germany

Facility Name

City

Mainz

ZIP/Postal Code

55131

Country

Germany

Facility Name

City

München

ZIP/Postal Code

81675

Country

Germany

Facility Name

City

Tubingen

ZIP/Postal Code

72076

Country

Germany

Facility Name

City

Hong Kong

Country

Hong Kong

Facility Name

City

Hong Kong

Country

Hong Kong

Facility Name

City

Kowloon

Country

Hong Kong

Facility Name

City

ShaTin

Country

Hong Kong

Facility Name

City

Tuen Mun

Country

Hong Kong

Facility Name

City

Haifa

ZIP/Postal Code

3109601

Country

Israel

Facility Name

City

Tel Aviv

ZIP/Postal Code

6423906

Country

Israel

Facility Name

City

Benevento

ZIP/Postal Code

82100

Country

Italy

Facility Name

City

Bologna

ZIP/Postal Code

40138

Country

Italy

Facility Name

City

Cremona

ZIP/Postal Code

26100

Country

Italy

Facility Name

City

Padova

ZIP/Postal Code

35128

Country

Italy

Facility Name

City

Rome

ZIP/Postal Code

00168

Country

Italy

Facility Name

City

Chuo Ku

ZIP/Postal Code

104-0045

Country

Japan

Facility Name

City

Fukuoka

ZIP/Postal Code

810-8563

Country

Japan

Facility Name

City

Fukuoka

ZIP/Postal Code

811-1395

Country

Japan

Facility Name

City

Iizuka

ZIP/Postal Code

820-8505

Country

Japan

Facility Name

City

Kanazawa

ZIP/Postal Code

920-8641

Country

Japan

Facility Name

City

Kashiwa

ZIP/Postal Code

277 8577

Country

Japan

Facility Name

City

Kyoto

ZIP/Postal Code

606-8507

Country

Japan

Facility Name

City

Matsuyama

ZIP/Postal Code

791-0280

Country

Japan

Facility Name

City

Osaka

ZIP/Postal Code

589-8511

Country

Japan

Facility Name

City

Shimotsuke

ZIP/Postal Code

329-0498

Country

Japan

Facility Name

City

Suita-shi

ZIP/Postal Code

565-0871

Country

Japan

Facility Name

City

Sunto-Gun

ZIP/Postal Code

411-8777

Country

Japan

Facility Name

City

Tokyo

ZIP/Postal Code

101-0062

Country

Japan

Facility Name

City

Yokohama

ZIP/Postal Code

241-8515

Country

Japan

Facility Name

City

Ōsaka

ZIP/Postal Code

541-8567

Country

Japan

Facility Name

City

Incheon

ZIP/Postal Code

21565

Country

Korea, Republic of

Facility Name

City

Seoul

ZIP/Postal Code

03080

Country

Korea, Republic of

Facility Name

City

Seoul

ZIP/Postal Code

03722

Country

Korea, Republic of

Facility Name

City

Seoul

ZIP/Postal Code

05505

Country

Korea, Republic of

Facility Name

City

Seoul

ZIP/Postal Code

06351

Country

Korea, Republic of

Facility Name

City

Ulsan

ZIP/Postal Code

44033

Country

Korea, Republic of

Facility Name

City

Gdansk

ZIP/Postal Code

80-219

Country

Poland

Facility Name

City

Poznan

ZIP/Postal Code

61-866

Country

Poland

Facility Name

City

Warszawa

ZIP/Postal Code

01-748

Country

Poland

Facility Name

Hospital Universitari de Girona Dr. Josep Trueta

City

Girona

ZIP/Postal Code

17007

Country

Spain

Facility Name

Hospital Clínico San Carlos

City

Madrid

ZIP/Postal Code

28040

Country

Spain

Facility Name

City

Santander

ZIP/Postal Code

39008

Country

Spain

Facility Name

City

Valencia

ZIP/Postal Code

46026

Country

Spain

Facility Name

City

Bern

ZIP/Postal Code

3010

Country

Switzerland

Facility Name

City

Kaohsiung city

ZIP/Postal Code

83301

Country

Taiwan

Facility Name

City

Puzi City

ZIP/Postal Code

61363

Country

Taiwan

Facility Name

City

Taichung

ZIP/Postal Code

40705

Country

Taiwan

Facility Name

City

Tainan

ZIP/Postal Code

704

Country

Taiwan

Facility Name

City

Tainan

ZIP/Postal Code

71004

Country

Taiwan

Facility Name

City

Tainan

ZIP/Postal Code

736

Country

Taiwan

Facility Name

City

Taipei city

ZIP/Postal Code

10048

Country

Taiwan

Facility Name

City

Taipei city

ZIP/Postal Code

11217

Country

Taiwan

Facility Name

City

Taoyuan City

ZIP/Postal Code

33305

Country

Taiwan

Facility Name

City

Acton

ZIP/Postal Code

W12 0HS

Country

United Kingdom

Facility Name

City

Acton

ZIP/Postal Code

w120hs

Country

United Kingdom

Facility Name

City

Bebington

ZIP/Postal Code

CH63 4JY

Country

United Kingdom

Facility Name

City

Birmingham

ZIP/Postal Code

B15 2TH

Country

United Kingdom

Facility Name

City

London

ZIP/Postal Code

NW3 2QG

Country

United Kingdom

Facility Name

City

London

ZIP/Postal Code

SE5 9RS

Country

United Kingdom

Facility Name

City

Manchester

ZIP/Postal Code

M20 4BX

Country

United Kingdom

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

IPD Sharing Time Frame

Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.

IPD Sharing Access Criteria

A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.

IPD Sharing URL

https://www.clinicalstudydatarequest.com/

Citations:

PubMed Identifier

36247923

Citation

Shao G, Bai Y, Yuan X, Chen X, Gu S, Gu K, Hu C, Liang H, Guo Y, Wang J, Yen CJ, Lee VH, Wang C, Widau RC, Zhang W, Liu J, Zhang Q, Qin S. Ramucirumab as second-line treatment in Chinese patients with advanced hepatocellular carcinoma and elevated alpha-fetoprotein after sorafenib (REACH-2 China): A randomised, multicentre, double-blind study. EClinicalMedicine. 2022 Oct 6;54:101679. doi: 10.1016/j.eclinm.2022.101679. eCollection 2022 Dec.

Results Reference

derived

PubMed Identifier

35247922

Citation

Llovet JM, Singal AG, Villanueva A, Finn RS, Kudo M, Galle PR, Ikeda M, Callies S, McGrath LM, Wang C, Abada P, Widau RC, Gonzalez-Gugel E, Zhu AX. Prognostic and Predictive Factors in Patients with Advanced HCC and Elevated Alpha-Fetoprotein Treated with Ramucirumab in Two Randomized Phase III Trials. Clin Cancer Res. 2022 Jun 1;28(11):2297-2305. doi: 10.1158/1078-0432.CCR-21-4000.

Results Reference

derived

PubMed Identifier

34795131

Citation

Mitani S, Chen Y, Inoue K, Mori J, Gao L, Long A, Wakabayashi S. Clinical Impact of a Shortened Infusion Duration of Ramucirumab in Japanese Patients -A Model-Based Approach. Gan To Kagaku Ryoho. 2021 Nov;48(11):1381-1387.

Results Reference

derived

PubMed Identifier

33822328

Citation

Trojan J, Mollon P, Daniele B, Marteau F, Martin L, Li Y, Xu Q, Piscaglia F, Zaucha R, Sarker D, Lim HY, Venerito M. Comparative Efficacy of Cabozantinib and Ramucirumab After Sorafenib for Patients with Hepatocellular Carcinoma and Alpha-fetoprotein >/= 400 ng/mL: A Matching-Adjusted Indirect Comparison. Adv Ther. 2021 May;38(5):2472-2490. doi: 10.1007/s12325-021-01700-2. Epub 2021 Apr 6.

Results Reference

derived

PubMed Identifier

33531690

Citation

Zhu AX, Finn RS, Kang YK, Yen CJ, Galle PR, Llovet JM, Assenat E, Brandi G, Motomura K, Ohno I, Daniele B, Vogel A, Yamashita T, Hsu CH, Gerken G, Bilbruck J, Hsu Y, Liang K, Widau RC, Wang C, Abada P, Kudo M. Serum alpha-fetoprotein and clinical outcomes in patients with advanced hepatocellular carcinoma treated with ramucirumab. Br J Cancer. 2021 Apr;124(8):1388-1397. doi: 10.1038/s41416-021-01260-w. Epub 2021 Feb 3.

Results Reference

derived

PubMed Identifier

33188713

Citation

Reig M, Galle PR, Kudo M, Finn R, Llovet JM, Metti AL, Schelman WR, Liang K, Wang C, Widau RC, Abada P, Zhu AX. Pattern of progression in advanced hepatocellular carcinoma treated with ramucirumab. Liver Int. 2021 Mar;41(3):598-607. doi: 10.1111/liv.14731. Epub 2020 Dec 5.

Results Reference

derived

PubMed Identifier

32817068

Citation

Zhu AX, Nipp RD, Finn RS, Galle PR, Llovet JM, Blanc JF, Okusaka T, Chau I, Cella D, Girvan A, Gable J, Bowman L, Wang C, Hsu Y, Abada PB, Kudo M. Ramucirumab in the second-line for patients with hepatocellular carcinoma and elevated alpha-fetoprotein: patient-reported outcomes across two randomised clinical trials. ESMO Open. 2020 Aug;5(4):e000797. doi: 10.1136/esmoopen-2020-000797.

Results Reference

derived

PubMed Identifier

32107609

Citation

Kudo M, Okusaka T, Motomura K, Ohno I, Morimoto M, Seo S, Wada Y, Sato S, Yamashita T, Furukawa M, Aramaki T, Nadano S, Ohkawa K, Fujii H, Kudo T, Furuse J, Takai H, Homma G, Yoshikawa R, Zhu AX. Ramucirumab after prior sorafenib in patients with advanced hepatocellular carcinoma and elevated alpha-fetoprotein: Japanese subgroup analysis of the REACH-2 trial. J Gastroenterol. 2020 Jun;55(6):627-639. doi: 10.1007/s00535-020-01668-w. Epub 2020 Feb 27.

Results Reference

derived

PubMed Identifier

30665869

Citation

Zhu AX, Kang YK, Yen CJ, Finn RS, Galle PR, Llovet JM, Assenat E, Brandi G, Pracht M, Lim HY, Rau KM, Motomura K, Ohno I, Merle P, Daniele B, Shin DB, Gerken G, Borg C, Hiriart JB, Okusaka T, Morimoto M, Hsu Y, Abada PB, Kudo M; REACH-2 study investigators. Ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increased alpha-fetoprotein concentrations (REACH-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019 Feb;20(2):282-296. doi: 10.1016/S1470-2045(18)30937-9. Epub 2019 Jan 18.

Results Reference

derived

Links:

URL

https://trials.lillytrialguide.com/en-US/trial/12euK0N4aQe2aiGqC6GEQ4

Description

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

Learn more about this trial

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

We'll reach out to this number within 24 hrs