Lenvatinib Plus HAIC of Modified FOLFOX Regime vs Lenvatinib Plus HAIC of ROX Regime in Patients With Advanced HCC

August 12, 2021 updated by: Zhejiang Cancer Hospital

Lenvatinib Combined With Hepatic Arterial Infusion of Modified FOLFOX Regimen Versus Lenvatinib Combined With Hepatic Arterial Infusion of ROX Regimen in the Treatment of Advanced Hepatocellular Carcinoma

Lenvatinib Plus Hepatic Arterial Infusion of Modified FOLFOX Regime vs Lenvatinib Plus Hepatic Arterial Infusion of Oxaliplatin Plus Raltitrexed in Patients with Advanced Hepatocellular Carcinoma

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Enrolling by invitation

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Hepatic arterial infusion chemotherapy is one of the important means for the treatment of advanced liver cancer. A multicenter randomized controlled study has confirmed that modified FOLFOX hepatic arterial infusion chemotherapy can significantly improve the prognosis of patients with advanced liver cancer and prolong the survival period of patients. The 2020 edition of CSCO guidelines for the diagnosis and treatment of liver cancer has recommended oxaliplatin based FOLFOX arterial infusion regimen as the first-line treatment of advanced liver cancer. FOLFOX regimen is safe and effective, but fluorouracil needs more than 46 hours of long-term infusion, patients have difficulty in moving during catheterization, and increase the risk of thrombosis, so it is urgent to find a short-term infusion of fluorouracil. As a new antimetabolic drug, raltitrexed can be used for short-term infusion, and its plasma concentration half-life is longer than that of fluorouracil. Previous studies have shown that compared with FOLFOX arterial infusion regimen, oxaliplatin combined with raltitrexed regimen has longer overall survival (OS) and progression free survival (PFS) in the treatment of advanced liver cancer. In addition, as an advanced liver cancer, lenvastinib has been recommended as a targeted drug for the first-line treatment of advanced HCC. This study intends to explore the efficacy and safety of modified FOLFOX regimen compared with oxaliplatin combined with raltitrexed (Rox regimen) in the treatment of lenvastinib combined with HAIC, so as to provide more clinical schemes for further improving the survival rate of patients with advanced liver cancer.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
60

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Early 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

  • China
    • Zhejiang
      • Hangzhou, Zhejiang, China, 310022
        • The Cancer Hospital of the University of Chinese Academy of Sciences（Zhejiang Cancer Hospital）

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Voluntary participation and informed consent, aged 18-75;
  2. Patients with HCC confirmed by histopathology or meeting the clinical diagnostic criteria in the 2019 edition of the diagnostic and therapeutic criteria for primary liver cancer;
  3. BCLC stage C patients with vascular invasion and without extrahepatic metastasis;
  4. Child Pugh liver function classification: A or B grade;
  5. ECOG physical strength score was 0-2 points;
  6. No previous systemic or local treatment, and the expected survival time is more than 3 months;
  7. According to recist1.1, the patient must have at least one measurable target lesion that has passed CT or MRI examination, and the tumor imaging evaluation was conducted within 2 weeks before receiving the study drug;
  8. Full organ and bone marrow function: WBC ≥ 3.0 × 109/L； NE≥1.5 × 109/L； PLT≥75 × 109/L； Liver and kidney function ALT and AST ≤ 5uln; TBIL≤2ULN； Albumin ≥ 28g / L; Cr≤1.5 ULN； International normalized ratio (INR) ≤ 1.5 or prothrombin time (PT) exceeding the normal control range ≤ 4 seconds;

Exclusion Criteria:

  1. Hepatocholangiocarcinoma, mixed cell carcinoma and fibrolamellar cell carcinoma are known;
  2. Uncontrollable ascites, hepatic encephalopathy or esophageal variceal bleeding;
  3. Patients with hypertension who can not be reduced to normal range after antihypertensive drug treatment (systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg);
  4. Patients with myocardial ischemia or myocardial infarction above grade II, poorly controlled arrhythmia, myocardial ischemia or myocardial infarction above grade II, poorly controlled arrhythmia (QTc interval ≥ 450 ms) (QTc interval was calculated by fridericia formula);
  5. Patients with history of gastrointestinal bleeding or definite tendency of gastrointestinal bleeding in the past 3 months, such as esophageal varices with bleeding risk, local active ulcer lesions, fecal occult blood ≥ +, can not be included in the group;
  6. Pregnant or lactating women, patients with fertility are unwilling or unable to take effective contraceptive measures;
  7. patients with a history of HIV infection;
  8. The researcher judges other situations that may affect the clinical research and the judgment of research results;

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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Lenvatinib，Then HAIC of mFOLFOX regimen
Cohort1：Participants were treated with 8mg lenvatinib (weight<60kg) or 12mg lenvatinib (weight>60kg) orally once daily on days 1 through 21, and HAIC regimen was performed every 3 weeks. The mFOLFOX regimen was administered via hepatic artery: oxaliplatin , 85mg/m2 , from hour 0 to 2 on day1 ; leucovorin , 400mg/m2 , from hour 2 to 3 on day 1 ; fluorouracil , 400mg/m2 , bolus at hour 3 ; and 2400mg/m2 over 46 hours on days 1 and 2.
Drug: Lenvatinib
8mg lenvatinib (weight<60kg) or 12mg lenvatinib (weight>60kg) QD
Other Names:
  • LENVIMA
Drug: mFOLFOX regimen
HAIC was performed every 3 weeks. The mFOLFOX regimen was administered via hepatic artery: oxaliplatin , 85mg/m2 , from hour 0 to 2 on day1 ; leucovorin , 400mg/m2 , from hour 2 to 3 on day 1 ; fluorouracil , 400mg/m2 , bolus at hour 3 ; and 2400mg/m2 over 46 hours on days 1 and 2.3mg/m2 , from hour 4 to 5 on day 1.
Other Names:
  • Oxaliplatin+Leucovorin+Fluorouracil
Experimental: Lenvatinib，Then HAIC of ROX regimen
Cohort2：Participants were treated with 8mg lenvatinib (weight<60kg) or 12mg lenvatinib (weight>60kg) orally once daily on days 1 through 21, and HAIC regimen was performed every 3 weeks. The ROX regimen was administered via hepatic artery: oxaliplatin , 100mg/m2 , from hour 0 to 4 on day1 ;raltitrexed , 3mg/m2 , from hour 4 to 5 on day 1.
Drug: Lenvatinib
8mg lenvatinib (weight<60kg) or 12mg lenvatinib (weight>60kg) QD
Other Names:
  • LENVIMA
Drug: ROX regimen
HAIC was performed every 3 weeks. The ROX regimen was administered via hepatic artery: oxaliplatin , 100mg/m2 , from hour 0 to 4 on day1 ;raltitrexed , 3mg/m2 , from hour 4 to 5 on day 1.
Other Names:
  • Raltitrexed+Oxaliplatin

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Objective Response Rate and Disease Control Rate of the HCC Participants
Time Frame: from admission to discharge, up to 4 weeks
ORR and DCR are validated indicators of the short-term clinical effects of hepatocellular carcinoma
from admission to discharge, up to 4 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Overall Survival and Progression-free Survival of the HCC Participants
Time Frame: six months and twelve months
OS and PFS are validated indicators of the long-term clinical effects of hepatocellular carcinoma
six months and twelve months
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0
Time Frame: from admission to discharge, up to 4 weeks
Treatment-Related Adverse Events are important indicators of the safety for tumor treatment
from admission to discharge, up to 4 weeks

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Weight and Height
Time Frame: from admission to discharge, up to 1 week
Weight and Height will be combined to report BMI in kg/m^2
from admission to discharge, up to 1 week
Age
Time Frame: from admission to discharge, up to 1 week
Age is divided into >50 and ≤50
from admission to discharge, up to 1 week
Sex
Time Frame: from admission to discharge, up to 1 week
Sex is divided into Male and Female
from admission to discharge, up to 1 week
ECOG score
Time Frame: from admission to discharge, up to 1 week
ECOG score is divided into 0,1,2
from admission to discharge, up to 1 week
Tumor size
Time Frame: from admission to discharge, up to 1 week
Tumor size is divided into >10cm and ≤10cm
from admission to discharge, up to 1 week
Tumor number
Time Frame: from admission to discharge, up to 1 week
Tumor number is divided into single and multiple
from admission to discharge, up to 1 week
AFP
Time Frame: from admission to discharge, up to 1 week
AFP is divided into >1000ug/L and ≤1000ug/L
from admission to discharge, up to 1 week
Portal vein invasion
Time Frame: from admission to discharge, up to 1 week
Portal vein invasion is divided into Vp1-2, Vp3, Vp4
from admission to discharge, up to 1 week
Extrahepatic spread
Time Frame: from admission to discharge, up to 1 week
Extrahepatic spread is divided into Yes and No
from admission to discharge, up to 1 week
Hepatitis B infection
Time Frame: from admission to discharge, up to 1 week
Hepatitis B infection is divided into Yes and No
from admission to discharge, up to 1 week

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Zhejiang Cancer Hospital

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
First Affiliated Hospital of Zhejiang University
Second Affiliated Hospital of Wenzhou Medical University
First Affiliated Hospital of Wenzhou Medical University
Shaoxing People's Hospital
Jinhua Central Hospital
The Third Affiliated Hospital of Wenzhou Medical University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Jiaping Zheng, Doctor, Zhejiang Cancer Hospital

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 (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 1, 2021

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 30, 2022

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 30, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 21, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 12, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 16, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 16, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 12, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ZJPIRB-2021-211

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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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