Carcinoma, HepatocellularPhase 1NCT02069041
A Study of Ramucirumab (LY3009806) in Participants With Advanced Liver Cancer
A Phase 1 study testing Ramucirumab and FOLFOX4 in people with Carcinoma, Hepatocellular, run by Eli Lilly and Company at 3 sites in Taiwan.
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. Read more about this study
- Who is it for?
- Ages 20 to 75 years
- Conditions the study is for
- Carcinoma, Hepatocellular
- What is being tested?
- Ramucirumab and FOLFOX4
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 3 sitesTaiwan
- Study dates
- Apr 2014to Sep 2016
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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 locations and contacts
3 sites in 1 country.
Taiwan3 sites
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, 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, 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, 33305
About this study
Official title: 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.
- Conditions
- Carcinoma, Hepatocellular
- Being tested
- Ramucirumab, FOLFOX4
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RamucirumabBiological
Also called IMC-1121B, LY3009806
Administered IV.
FOLFOX4Drug
Also called FOLFOX4 (leucovorin + fluorouracil + oxaliplatin)
Administered IV.
| Study group | Role | What they receive |
|---|---|---|
| Ramucirumab + FOLFOX4 | Experimental | 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. Receives: Biological: Ramucirumab; Drug: FOLFOX4 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline through study completion (Up To 8 Months)
Secondary outcomes (4)
Pharmacokinetics (PK): Maximum Concentration (Cmax) of Ramucirumab
Maximum Concentration (Cmax)
Measured: 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
Area under the concentration-time curve.
Measured: 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
Measured: Baseline through 6.1 Months
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.
Measured: Response to Disease Progression or Death (Up To 7 Months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2014 (estimated)
- Study startApr 2014
- Primary completionSep 2016
- Study completionSep 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Carcinoma, HepatocellularStudies of the same condition, open and under way.
- More trials run by Eli Lilly and CompanyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eli Lilly and Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- 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), Study director, Eli Lilly and Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02069041
- Sponsor's protocol ID
- 15233
- Other IDs
- I4T-CR-JVCQ
- Status last verified
- Sep 2017
- First submitted
- 20 Feb 2014
- Last updated
- 21 Nov 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 33017497
Study at a glance
From the registry record, last updated by the sponsor on 21 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1b Study of 5-FU/FA and Oxaliplatin (FOLFOX4) Plus Ramucirumab (LY3009806) in Patients With Advanced Hepatocellular Carcinoma
- ClinicalTrials.gov ID
- NCT02069041
- Acronym / sponsor ID
- 15233
- Conditions
- Carcinoma, Hepatocellular
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Eli Lilly and CompanyIndustry (pharma, biotech, devices)
- Study start
- Apr 2014
- Primary completion
- Sep 2016 (actual)
- Study completion
- Sep 2016 (actual)
- First posted
- 21 Feb 2014 (estimated)
- Results
- Posted 21 Nov 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ramucirumab + FOLFOX4 | Experimental | Biological: Ramucirumab, Drug: FOLFOX48 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. |
Who may qualify
- Ages
- 20 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (26 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RamucirumabAlso: IMC-1121B, LY3009806Administered IV. | Biological | Ramucirumab + FOLFOX4 |
| FOLFOX4Also: FOLFOX4 (leucovorin + fluorouracil + oxaliplatin)Administered IV. | Drug | Ramucirumab + FOLFOX4 |
Primary outcome
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.
4 secondary outcomes
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
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
Number of Participants With Anti-Ramucirumab Antibodies
Time frame: 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)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Nov 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33017497Lin 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
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) study director
Eli Lilly and Company
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ramucirumab and FOLFOX4 in people with Carcinoma, Hepatocellular, run by Eli Lilly and Company at 3 sites in Taiwan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Nov 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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 (Up To 8 Months)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02069041, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Nov 2018.