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

May 3, 2018 updated by: Eli Lilly and Company

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

8

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Taiwan
      • Tainan, Taiwan, 70403
        • 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, 10048
        • 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, Taiwan, 33305
        • 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.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Ramucirumab + FOLFOX4

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.
Biological: Ramucirumab
Administered IV.
Other Names:
  • LY3009806
  • IMC-1121B
Drug: FOLFOX4
Administered IV.
Other Names:
  • FOLFOX4 (leucovorin + fluorouracil + oxaliplatin)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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 (Up To 8 Months)
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pharmacokinetics (PK): Maximum Concentration (Cmax) of Ramucirumab
Time Frame: 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
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
PK:Area Under the Concentration-Time Curve (AUC[0-∞]) of Ramucirumab
Time Frame: 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
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
Number of Participants With Anti-Ramucirumab Antibodies
Time Frame: Baseline through 6.1 Months
Baseline through 6.1 Months
Percentage of Participants With Best Response of Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR])
Time Frame: Response to Disease Progression or Death (Up To 7 Months)

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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Eli Lilly and Company

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2014

Primary Completion (Actual)

September 1, 2016

Study Completion (Actual)

September 1, 2016

Study Registration Dates

First Submitted

February 20, 2014

First Submitted That Met QC Criteria

February 20, 2014

First Posted (Estimate)

February 21, 2014

Study Record Updates

Last Update Posted (Actual)

November 21, 2018

Last Update Submitted That Met QC Criteria

May 3, 2018

Last Verified

September 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 15233
  • I4T-CR-JVCQ (Other Identifier: Eli Lilly and Company)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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