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

Carcinoma, Hepatocellular Clinical Trial

Official title:

Phase 1b Study of 5-FU/FA and Oxaliplatin (FOLFOX4) Plus Ramucirumab (LY3009806) in Patients With Advanced Hepatocellular Carcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02069041
• Other study ID #: 15233
• Secondary ID: I4T-CR-JVCQ
• Status: Completed
• Phase: Phase 1
• Start date: April 2014
• Est. completion date: September 2016

Study information

• Verified date: September 2017
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: September 2016
• Est. primary completion date: September 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular

Intervention

Biological:
• Ramucirumab
Administered IV.

Drug:
• FOLFOX4
Administered IV.

Locations

Country	Name	City	State
Taiwan	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.	Tainan
Taiwan	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.	Taipei
Taiwan	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.	Taoyuan City

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration	A summary of other non-serious Adverse Events (AEs), and all Serious Adverse Events (SAE's), regardless of causality, is located in the Reported Adverse Events section.	Baseline through study completion (Up To 8 Months)
Secondary	Pharmacokinetics (PK): Maximum Concentration (Cmax) of Ramucirumab	Maximum Concentration (Cmax)	Cycle 1 and Cycle 3: 0,1.0,1.5,2.0,3.0,5.0,24.0,48.0,168.0,336.0 hours
Secondary	PK:Area Under the Concentration-Time Curve (AUC[0-8]) of Ramucirumab	Area under the concentration-time curve.	Cycle 1 and Cycle 3: 0,1.0,1.5,2.0,3.0,5.0,24.0,48.0,168.0,336.0 hours
Secondary	Number of Participants With Anti-Ramucirumab Antibodies		Baseline through 6.1 Months
Secondary	Percentage of Participants With Best Response of Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR])	Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST, version[v] 1.1) criteria.CR was defined as the disappearance of all target and non-target lesions and all target and non-target lymph nodes were non-pathological or normal in size [<10 millimeter (mm) short axis]. PR is at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters. Progressive Disease(PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (including the baseline sum if that is the smallest).In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.; Percentage of participants with CR or PR= (number of participants whose best overall response was CR or PR)/(number of participants treated)*100.	Response to Disease Progression or Death (Up To 7 Months)