- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04127396
Lenvatinib Plus TACE Versus Sorafenib Plus TACE for HCC With PVTT
Exploring Lenvatinib Plus TACE Versus Sorafenib Plus TACE for Hepatocellular Carcinoma Patients With Portal Vein Tumor Thrombus: Efficacy, Safety and Outcome Analysis
Hepatocellular carcinoma (HCC) is the fourth most common cancer in China, with a crude incidence rate of 26.67 per 100,000 population. Moreover, 357,800 new liver cancer cases are predicted to be diagnosed in China in 2020. HCC represents approximately 90% of all cases of primary liver cancer. HCC has a high predilection for portal vein invasion, which occurs in 44-62% of living patients with HCC. Patients with PVTT usually have an aggressive disease course, decreased liver function reserve, limited treatment options, thus worse overall survival. Among untreated HCC patients with PVTT, the median overall survival has been reported as low as 2 to 4 months with supportive care. Sorafenib is the first-line treatment for HCC patients with PVTT, however, it has shown unsatisfactory benefit. Notably, sorafenib combined with TACE significantly improved the TTP over sorafenib alone, albeit for no more than 1 month in the median TTP, and the median OS was not significantly prolonged. A promising drug-lenvatinib was approved in China on September 2018, in the China patients subgroup analysis showed an encouraging results. Lenvatinib group had showed a significant benefit in TTP, PFS and ORR. Also median overall survival time was significantly improved in China subgroup (Lenvatinib group: 15 months VS Sorafenib group: 10.2 months). However, REFLECT didn't enrolled patients who had tumors invading the maint portal vein. The mechanisms of lenvatinib or sorafenib combined with TACE were still unknown, and clinical data were limited.
This study was to explore lenvatinib plus TACE versus sorafenib plus TACE for HCC with PVTT: efficacy and safety. Biomarkers expression of VEGFR, FGFR, FDGF-α, IL-2,etc would be detected to find the difference between the two groups, finally to analyze the relationship between clinical outcomes and biomarkers' expression. A better treatment modality to HCC with PVTT patients would be expected and promoted.
Study Overview
Status
Detailed Description
Hepatocellular carcinoma (HCC) is the fourth most common cancer in China, with a crude incidence rate of 26.67 per 100,000 population. Moreover, 357,800 new liver cancer cases are predicted to be diagnosed in China in 2020, and HCC is by far the most common subtype of primary liver cancer and is the second most frequent cause of cancer-related death in the country. Approximately 80% of liver cancers are attributed to chronic infection with hepatitis B virus (HBV) and hepatitis C virus; other factors, including diabetes mellitus, non-alcoholic fatty liver disease, alcohol consumption, and tobacco use, have also been found to be potential risk factors for liver cancer HCC has a high predilection for portal vein invasion, which occurs in 44-62% of living patients with HCC. Portal vein tumour thrombosis (PVTT) usually portends a worse prognosis, with a median survival time of only 2.7-4.0 months in untreated patients. Despite advancements in understanding the molecular aetiology of HCC, the outcomes for patients with this disease who develop PVTT remain unsatisfactory.
Several treatment strategies for patients with inoperable HCC who developed PVTT have been attempted, including first-line targeted therapy with sorafenib, transarterial chemoembolisation (TACE), TACE plus sorafenib, percutaneous radiofrequency ablation (RFA), and radiotherapy. However, the prognosis of patients with HCC who are complicated by PVTT remains poor, and the optimal treatment modality for such patients has not been established to date.
Notably, sorafenib combined with TACE significantly improved the TTP over sorafenib alone, albeit for no more than 1 month; the median TTP was less than 3 months, and the median OS was not significantly prolonged.
In the recent phase III global multicentre REFLECT study, lenvatinib, the only other available first-line anti-angiogenic drug, did not improve overall survival (OS). However, lenvatinib as an oral multikinase inhibitor that targets VEGF receptors 1-3, FGF receptors 1-4, PDGF receptor α, RET and KIT, median time of PFS was 8.9 months (95% CI 7.4-9.2) for patients in the lenvatinib group compared to 3.7 months (95% CI 3.6-5.4) for patients in the sorafenib group. Lenvatinib also showed a greater objective response rate (ORR) than did sorafenib group. ORR was 40.6% (95% CI 36.2-45.0) for patients in the lenvatinib group compared to 12.4% (95% CI 9.4-15.4) for patients in the sorafenib group, and TTP was 7.4 (95% CI 7.2-9.1) VS 3.7 (95% CI 3.6-3.9). What's more, in the Chinese patients subgroup analysis showed an encouraging results, lenvatinib group not only showed significant improvement in PFS, TTP, ORR, but also in median OS time ( Lenvatinib group: 15 months VS sorafenib group 10.2 months). However, REFLECT didn't enrolled patients who had tumors invading the maint portal vein.
However, the mechanism of sorafenib combined with TACE was unknown, and clinical data of TACE plus lenvatinib for HCC had not been reported until now. As our preliminary experimental results showed that lenvatinib combined with TACE show a 91.7% clinical benefit in 11 cases HCC with PVTT (7 PR cases, 4 SD cases) , the median TTP was 6.5 months, during the preliminary experimental trail hadn't observed any fatal adverse event occurred.
In addition to these supporting data, lenvatinib plus TACE showed a potential benefit to HCC with PVTT patients. This study was to explore lenvatinib plus TACE versus sorafenib plus TACE for HCC with PVTT: efficacy and safety. Biomarkers expression of VEGFR, FGFR, PDGF-α, IL-2,etc would be detected to find the difference between the two groups, finally to analyze the relationship between clinical outcomes and biomarkers' expression.
Study Type
Enrollment (Anticipated)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
Beijing
-
Beijing, Beijing, China, 100011
- Beijing Ditan Hospital, Capital Medical University
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria
- Histologically or cytologically proven HCC.
- HCC complicated by PVTT.
- Patient had not received previous systemic therapy.
- At least one measurable tumor along a single dimension according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST).
- WBC ≥ 3.0*109/L,PLT≥70*109/L,Hgb≥80*109/L;ALT≤2.5ULN,AST≤2.5ULN,TBIL≤3ULN,ALB≥28g/L;CCr ≥80ml/min.
- Patients had not history of previous local therapy such as radiotherapy, hepatic arterial embolisation, chemoembolisation, RFA, percutaneous injection, or cryoablation.
- Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0 or 1;
- Child-Pugh class A or Child-Pugh class B (score 7).
- All patients were voluntary, and signed informed agreement.
Exclusion criteria
- Previous or concomitant systemic therapy (including molecularly targeted therapies).
- Known history of HIV infection.
- Clinically serious infections.
- Administered warfarin as an anticoagulant.
- History of organ allograft.
- History of cardiac disease.
- Known central nervous system tumour.
- Known gastrointestinal bleeding up to 30 days before study enrolment,
- Pregnancy or breastfeeding.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: lenvatinib and TACE
Patients in Lenvatinib + TACE group will take oral lenvatinib within one day of randomization and receive TACE 1 day after oral administration of lenvatinib.
|
Lenvatinib capsules will be administered orally, once daily in continuous 28-day cycles.
Body weight (BW)>60 kilograms(kg)-Lenvatinib 12 mg (taken as three 4-mg capsules); BW<60kg-Lenvatinib 8 mg (taken as two 4-mg capsules)
Other Names:
TACE will be performed one day after oral administration of lenvatinib .
TACE with either cTACE or DEB-TACE can be used, depending on the condition of center.
TACE will be performed one day after oral administration of Sorafenib.
TACE with either cTACE or DEB-TACE can be used, depending on the condition of center.
|
Active Comparator: Sorafenib and TACE
Patients in Sorafenib + TACE group will take oral sorafenib within one day of randomization and receive TACE 1 day after oral administration of lenvatinib.
|
TACE will be performed one day after oral administration of lenvatinib .
TACE with either cTACE or DEB-TACE can be used, depending on the condition of center.
TACE will be performed one day after oral administration of Sorafenib.
TACE with either cTACE or DEB-TACE can be used, depending on the condition of center.
Sorafenib capsules will be administered orally, 400 mg twice daily (BID) oral dosing.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Time to progression
Time Frame: up to 18 months
|
The primary endpoint was TTP (defined as the date of randomization until progression). Treatment response was evaluated according to mRECIST combined with contrast-enhanced dynamic CT or magnetic resonance imaging. |
up to 18 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective response rate(ORR)
Time Frame: up to 18 months
|
ORR defined as the rate of patients with complete response or partial response according to mRECIST.
|
up to 18 months
|
overall survival(OS)
Time Frame: up to 18 months
|
OS defined as the date of randomization to death from any cause.
|
up to 18 months
|
adverse events(AEs)
Time Frame: up to 18 months
|
AEs(adverse events) evaluated by the CTC-AE 5.0.
|
up to 18 months
|
Collaborators and Investigators
Sponsor
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Cardiovascular Diseases
- Vascular Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Adenocarcinoma
- Neoplasms, Glandular and Epithelial
- Digestive System Neoplasms
- Liver Diseases
- Embolism and Thrombosis
- Liver Neoplasms
- Carcinoma
- Carcinoma, Hepatocellular
- Thrombosis
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Estrogens, Non-Steroidal
- Estrogens
- Protein Kinase Inhibitors
- Chlorotrianisene
- Sorafenib
- Lenvatinib
Other Study ID Numbers
- BeijingDH 001
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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.
Clinical Trials on Carcinoma, Hepatocellular
-
Academic and Community Cancer Research UnitedNational Cancer Institute (NCI)RecruitingUnresectable Hepatocellular Carcinoma | Stage III Hepatocellular Carcinoma AJCC v8 | Stage IIIA Hepatocellular Carcinoma AJCC v8 | Stage IV Hepatocellular Carcinoma AJCC v8 | Stage IVA Hepatocellular Carcinoma AJCC v8 | Stage IVB Hepatocellular Carcinoma AJCC v8 | BCLC Stage B Hepatocellular Carcinoma and other conditionsUnited States
-
Roswell Park Cancer InstituteMerck Sharp & Dohme LLCActive, not recruitingAdvanced Adult Hepatocellular Carcinoma | Child-Pugh Class A | Stage III Hepatocellular Carcinoma | Stage IIIA Hepatocellular Carcinoma | Stage IIIB Hepatocellular Carcinoma | Stage IIIC Hepatocellular Carcinoma | Stage IV Hepatocellular Carcinoma | Stage IVA Hepatocellular Carcinoma | Stage IVB Hepatocellular...United States
-
Roswell Park Cancer InstituteNational Comprehensive Cancer NetworkCompletedAdvanced Adult Hepatocellular Carcinoma | Localized Non-Resectable Adult Hepatocellular Carcinoma | Stage IIIA Hepatocellular Carcinoma | Stage IIIB Hepatocellular Carcinoma | Stage IIIC Hepatocellular Carcinoma | Stage IVA Hepatocellular Carcinoma | Stage IVB Hepatocellular Carcinoma | Stage III... and other conditionsUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)CompletedUnresectable Hepatocellular Carcinoma | Advanced Adult Hepatocellular Carcinoma | Stage IIIB Hepatocellular Carcinoma AJCC v7 | Stage IIIC Hepatocellular Carcinoma AJCC v7 | BCLC Stage C Hepatocellular Carcinoma | Stage IV Hepatocellular Carcinoma AJCC v7 | Stage III Hepatocellular Carcinoma AJCC... and other conditionsUnited States
-
Academic and Community Cancer Research UnitedNational Cancer Institute (NCI); Genentech, Inc.RecruitingUnresectable Hepatocellular Carcinoma | Stage III Hepatocellular Carcinoma AJCC v8 | Stage IIIA Hepatocellular Carcinoma AJCC v8 | Stage IV Hepatocellular Carcinoma AJCC v8 | Stage IVA Hepatocellular Carcinoma AJCC v8 | Stage IVB Hepatocellular Carcinoma AJCC v8 | Stage IIIB Hepatocellular Carcinoma... and other conditionsUnited States
-
National Cancer Institute (NCI)CompletedUnresectable Hepatocellular Carcinoma | Advanced Adult Hepatocellular Carcinoma | Recurrent Hepatocellular Carcinoma | Stage IIIB Hepatocellular Carcinoma AJCC v7 | Stage IIIC Hepatocellular Carcinoma AJCC v7 | Stage IV Hepatocellular Carcinoma AJCC v7 | Stage III Hepatocellular Carcinoma AJCC v7 and other conditionsUnited States, Canada, Puerto Rico
-
City of Hope Medical CenterNational Cancer Institute (NCI)RecruitingUnresectable Hepatocellular Carcinoma | Stage III Hepatocellular Carcinoma AJCC v8 | Stage IIIA Hepatocellular Carcinoma AJCC v8 | Stage IV Hepatocellular Carcinoma AJCC v8 | Stage IVA Hepatocellular Carcinoma AJCC v8 | Stage IVB Hepatocellular Carcinoma AJCC v8 | BCLC Stage B Hepatocellular Carcinoma and other conditionsUnited States
-
Mayo ClinicNational Cancer Institute (NCI)RecruitingAdvanced Hepatocellular Carcinoma | BCLC Stage B Hepatocellular Carcinoma | BCLC Stage C Hepatocellular Carcinoma | Metastatic Hepatocellular Carcinoma | BCLC Stage A Hepatocellular CarcinomaUnited States
-
Northwestern UniversityBristol-Myers Squibb; National Cancer Institute (NCI)CompletedStage IIIA Hepatocellular Carcinoma | Stage IIIB Hepatocellular Carcinoma | Stage IIIC Hepatocellular Carcinoma | Stage IVA Hepatocellular Carcinoma | Stage IVB Hepatocellular CarcinomaUnited States
-
OHSU Knight Cancer InstituteOregon Health and Science University; American Society of Clinical Oncology; Radiological... and other collaboratorsWithdrawnHepatocellular Carcinoma | Stage III Hepatocellular Carcinoma AJCC v8 | Stage IIIA Hepatocellular Carcinoma AJCC v8 | Stage IVA Hepatocellular Carcinoma AJCC v8 | Stage IIIB Hepatocellular Carcinoma AJCC v8 | Stage IB Hepatocellular Carcinoma AJCC v8 | Stage II Hepatocellular Carcinoma AJCC v8 | Stage... and other conditionsUnited States
Clinical Trials on Lenvatinib Pill
-
Memorial Sloan Kettering Cancer CenterCompletedHead and Neck Cancer | Head and Neck Squamous Cell Carcinoma | Head and Neck Carcinoma | Cutaneous Squamous Cell CarcinomaUnited States
-
Assistance Publique - Hôpitaux de ParisEisai Inc.Active, not recruitingHepatocellular CarcinomaFrance
-
National Health Research Institutes, TaiwanNational Taiwan University Hospital; Chang Gung Memorial Hospital; Kaohsiung... and other collaboratorsRecruitingAdvanced Biliary Tract CancerTaiwan
-
Fudan UniversityActive, not recruitingHepatocellular CarcinomaChina
-
Regina Elena Cancer InstituteUniversity of Pisa; University of Roma La Sapienza; University of Turin, Italy; Istituto Oncologico Veneto IRCCS and other collaboratorsRecruitingDifferentiated Thyroid Cancer | GenderItaly
-
Shanghai Junshi Bioscience Co., Ltd.Active, not recruitingAdvanced Hepatocellular Carcinoma (HCC)Italy, Poland, Singapore, United States, China, Ukraine
-
Shandong New Time Pharmaceutical Co., LTDRecruitingHepatocellular CarcinomaChina
-
Cancer Institute and Hospital, Chinese Academy...Active, not recruitingHepatocellular Carcinoma | Radiotherapy | LenvatinibChina
-
CStone PharmaceuticalsActive, not recruitingHepatocellular CarcinomaSpain, China, United States, Poland, Italy, Taiwan
-
University of Alabama at BirminghamCompletedObesity | Body Weight | Eating Behavior | HungerUnited States