Overview

This trial has been completed.

Condition carcinoma, hepatocellular
Treatments ramucirumab, folfox4
Phase phase 1
Target VEGF
Sponsor Eli Lilly and Company
Start date April 2014
End date September 2016
Trial size 9 participants
Trial identifier NCT02069041, 15233, I4T-CR-JVCQ

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
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. Participants may continue to receive treatment until discontinuation criteria are met.
ramucirumab IMC-1121B
Administered IV.
folfox4 FOLFOX4 (leucovorin + fluorouracil + oxaliplatin)
Administered IV.

Primary Outcomes

Measure
Number of Participants with One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration
time frame: Baseline through study completion (estimated as 8 months)

Secondary Outcomes

Measure
Pharmacokinetics: Maximum Concentration (Cmax) of Ramucirumab
time frame: Baseline through Cycle 9, Day 1 (Cycle = 2 weeks)
Pharmacokinetics: Area Under the Concentration Curve (AUC) of Ramucirumab
time frame: Baseline through Cycle 9, Day 1 (Cycle = 2 weeks)
Number of Participants with Anti-Ramucirumab Antibodies
time frame: Baseline through Cycle 9, Day 1 (Cycle = 2 weeks)
Objective Responses Rate (ORR)
time frame: Response to disease progression or death (estimated as 2 months)

Eligibility Criteria

Male or female participants from 20 years up to 75 years old.

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

Additional Information

Official title Phase 1b Study of 5-FU/FA and Oxaliplatin (FOLFOX4) Plus Ramucirumab (LY3009806) in Patients With Advanced Hepatocellular Carcinoma
Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by Eli Lilly and Company.