Lenvatinib Plus TACE Versus Sorafenib Plus TACE for HCC With PVTT

NCT04127396 | Unknown Phase 4 DMC

• 1 other identifier: BeijingDH 001
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Carcinoma, Hepatocellular; Portal Vein Tumor Thrombus

Keywords

Transarterial chemoembolization; hepatocellular carcinoma; portal vein tumor thrombus

Outcome Measures

Primary Outcomes (1)

• Time to progression

  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 Outcomes (3)

• Objective response rate(ORR)

  up to 18 months

• overall survival(OS)

  up to 18 months

• adverse events(AEs)

  up to 18 months

Study Arms (2)

lenvatinib and TACE

EXPERIMENTAL

Patients in Lenvatinib + TACE group will take oral lenvatinib within one day of randomization and receive TACE 1 day after oral administration of lenvatinib.

Drug: Lenvatinib Pill; Procedure: Transarterial chemoembolization(TACE)

Sorafenib and TACE

ACTIVE COMPARATOR

Patients in Sorafenib + TACE group will take oral sorafenib within one day of randomization and receive TACE 1 day after oral administration of lenvatinib.

Drug: Sorafenib; Procedure: Transarterial chemoembolization(TACE)

Interventions

Lenvatinib Pill DRUG

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)

Also known as: E7080

lenvatinib and TACE

Transarterial chemoembolization(TACE) PROCEDURE

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.

lenvatinib and TACE

Sorafenib DRUG

Sorafenib capsules will be administered orally, 400 mg twice daily (BID) oral dosing.

Sorafenib and TACE

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Beijing Ditan Hospital: lead

Study Sites (1)

Beijing Ditan Hospital, Capital Medical University

Beijing, Beijing Municipality, 100011, China

Location

Related Publications (1)

• Ding X, Sun W, Li W, Shen Y, Guo X, Teng Y, Liu X, Zheng L, Li W, Chen J. Transarterial chemoembolization plus lenvatinib versus transarterial chemoembolization plus sorafenib as first-line treatment for hepatocellular carcinoma with portal vein tumor thrombus: A prospective randomized study. Cancer. 2021 Oct 15;127(20):3782-3793. doi: 10.1002/cncr.33677. Epub 2021 Jul 8.

  PMID: 34237154 DERIVED

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

lenvatinib; Sorafenib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief of Oncology

Study Record Dates

• First Submitted: October 8, 2019
• First Posted: October 15, 2019
• Study Start: September 1, 2019
• Primary Completion: August 1, 2021
• Study Completion: December 1, 2021
• Last Updated: July 23, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)