A Study of Ramucirumab (LY3009806) in Participants With Advanced Liver Cancer

Lilly

Status and phase: Completed; Phase 1

Conditions: Carcinoma, Hepatocellular

Treatments: Drug: FOLFOX4; Biological: Ramucirumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT02069041

I4T-CR-JVCQ (Other Identifier)

15233

Details and patient eligibility

About

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.

Enrollment: 8 patients

Sex: All

Ages: 20 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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8 participants in 1 patient group

Ramucirumab + FOLFOX4

Experimental group

Description:

8 milligram/kilogram (mg/kg) ramucirumab given intravenously (IV) on Day 1 followed by FOLFOX4 (folinic acid + fluorouracil + oxaliplatin chemotherapy regimen) given IV on Day 1 of 2 week cycles: FOLFOX4 every 2 weeks: 85 milligram per square meter (mg/m²) oxaliplatin IV on Day 1 200 mg/m² folinic acid(FA) IV on days 1 and 2 400 mg/m² 5-FU bolus on days 1 and 2 600 mg/m2 5-FU 22-h continuous infusion on Days 1 and 2 Participants may continue to receive treatment until discontinuation criteria are met.

Treatment:

Biological: Ramucirumab

Drug: FOLFOX4