Clinical trial NCT02069041: A Study of Ramucirumab (LY3009806) in Participants With Advanced Liver Cancer
Official title: Phase 1b Study of 5-FU/FA and Oxaliplatin (FOLFOX4) Plus Ramucirumab (LY3009806) in Patients With Advanced Hepatocellular Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Carcinoma, Hepatocellular
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2014-02-21
Enrollment: 8
Sex: ALL
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

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
timeFrame: Baseline through study completion (Up To 8 Months)
Secondary outcomes:
measure: Pharmacokinetics (PK): Maximum Concentration (Cmax) of Ramucirumab
timeFrame: 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
measure: PK:Area Under the Concentration-Time Curve (AUC[0-∞]) of Ramucirumab
timeFrame: 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
measure: Number of Participants With Anti-Ramucirumab Antibodies
timeFrame: Baseline through 6.1 Months
measure: Percentage of Participants With Best Response of Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR])
timeFrame: Response to Disease Progression or Death (Up To 7 Months)
Other outcomes:
Locations:
city: Tainan
country: Taiwan
facility: 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: Taipei
country: Taiwan
facility: 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: Taoyuan City
country: Taiwan
facility: 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.
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References:
citation: Lin CC, Yang TS, Yen CJ, Cheng R, Liu J, Hsu C. Safety and Preliminary Efficacy of Ramucirumab in Combination with FOLFOX4 in Patients with Advanced Hepatocellular Carcinoma: A Nonrandomized, Open-Label, Phase Ib Study. Oncologist. 2020 Dec;25(12):e1921-e1929. doi: 10.1002/onco.13550. Epub 2020 Oct 31.