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Hepatocellular CarcinomaNCT04415567

Adjuvant Lenvatinib Prevents Recurrence of High-risk Patients With HBV-related HCC After Liver Transplantation

An observational study of Hepatocellular Carcinoma, run by Jinyang Gu at 1 site in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

High-risk patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) suffer from a high ratio of recurrence after liver transplantation (LT). Lenvatinib, as a novel targeted drug, has shown an excellent effect in the treatment of advanced HCC, but there is no study on its effect in preventing HCC… Read more about this study

Who is it for?
Ages 8 to 69 years
Conditions the study is for
Hepatocellular Carcinoma
What is being tested?
Lenvatinib
Type of treatment
Pill or oral medicine
How many people
23 participants
Where
1 siteChina
Study dates
1 Jun 2018to 31 Mar 2020
Phase
Observational
Are there results?
None posted in the registry

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 8 to 69 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Study population: The cohorts in the study involved the patients who underwent liver transplantation for HBV-related HCC and were diagnosed as "high-risk" for recurrence according the above criteria.

Who may be able to join

  • The recipients who underwent liver transplantation with the pathologic diagnosis of hepatocellular carcinoma.
  • The extrahepatic metastasis was excluded preoperatively.
  • The patients were defined as "high-risk" for recurrence according to the following criteria:
  • beyond Milan criteria confirmed either by radiology before LT or by pathology after LT, (2) tumor with intrahepatic vascular invasion, (3) Alpha-fetoprotein (AFP)≥400ng/L before LT, (4) presence of microvascular invasion (MVI), (5) tumor with histological poor differentiation according to Edmondson-Steiner classification system(21), (6) multiple satellite lesions around the largest tumors detected either by radiology before LT or by histology after LT, (7) tumor penetrating hepatic capsule, (8) recurrent HCC after resection. 4. ECOG score between 0-1 within 1 week before took lenvatinib. 5. The patients have received regular antiviral treatment. 6. Life expectancy more than 3 months.

Who cannot join

  • The patients took lenvatinib before liver transplantation and assessed as SD or PD according to the mRECIST criteria.
  • The patients suffered from other incurable malignancies within 5 years or at the same time.
  • Distant metastasis of tumor was confirmed by imaging before or within 1 month after transplantation.
  • The patients have not received regular antiviral treatment.
  • The patients had a history of mental illness or abuse of psychoactive drugs.
  • The patients deemed unsuitable by attending doctors.

Trial locations and contacts

1 site in 1 country.

China1 site
  • Xinhua Hospital Affiliated to Shanghai Jiao Tong University Medical School

    Shanghai, 200092

Other trials in China

About this study

Official title: Adjuvant Lenvatinib Prevents Recurrence of High-risk Patients With Hepatitis B Virus-related Hepatocellular Carcinoma Following Liver Transplantation: a Retrospective Case Control Study

High-risk patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) suffer from a high ratio of recurrence after liver transplantation (LT). Lenvatinib, as a novel targeted drug, has shown an excellent effect in the treatment of advanced HCC, but there is no study on its effect in preventing HCC recurrence in the patients undergoing transplantation. Therefore, to evaluate the role of adjuvant lenvatinib in preventing recurrence of high-risk LT recipients with HBV-related HCC, the investigators retrospectively analyzed 23 high-risk patients consisting of lenvatinib group (n=14) and control group (n=9) with HBV-related HCC who underwent LT. Disease-free survival (DFS) and HCC recurrence of the two groups were compared. The adverse events (AEs) and drug tolerance of lenvatinib were evaluated.

Read the detailed description

The investigators retrospectively reviewed 23 Chinese HCC patients with HBV infection, who underwent LT in our hospital from June 2018 to December 2019. All donor grafts were allocated by the China Organ Transplant Response System. All these patients were diagnosed by histology and were defined as "high-risk" for recurrence.

The participants were divided into lenvatinib group and control group according to their willingness to take lenvatinib as adjuvant therapy after LT. Of the 23 patients, 14 pantients in lenvatinib group began to take lenvatinib about a month after LT except for routine treatment, while the other 9 patients in control group received routine treatment and follow-up after transplantation. Clinical data and demographic characteristics was obtained. This study was conducted according to the 1975 Declaration of Helsinki and approved by Ethics Committee of Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (No. XHEC-D-2020-068). All patients enrolled in this study provided informed consent.

Usage of lenvatinib and immunosuppressants The participants in lenvatinib group received oral lenvatinib (Eisai, Japan) 12 mg/day (for bodyweight (BW) ≥60 kg) or 8 mg/day (for BW <60 kg) in 28-day cycles until HCC recurrence or serious adverse events (SAEs) or voluntary withdrawal. Dose interruptions followed by reductions for lenvatinib-related toxicities (to 8 mg and 4 mg/day, or 4 mg every other day) were permitted. All 14 patients took lenvatinib for more than 3 cycles.

The induction immunosuppression strategies for all participants enrolled in the study involved IV infusion of 20mg of basiliximab within 2 hours prior to operation and a second dose 4 days later, oral tacrolimus started on the fourth day after LT at a dose of 0.04mg/kg (BW) and adjusted according to its plasma concentration, taking mycophenolate mofetil (MMF) from the next day after surgery at a dose of 500mg/kg(BW), and rapid withdrawal of glucocorticoids with the initial dose of 500mg. Maintenance immunosuppression which was started about one month after LT included sirolimus (4 mg/M2 per day) plus oral tacrolimus with the plasma concentration maintained at 5-8 ng/ml.

All patients were followed up monthly within six months after LT and every three months within two years. During each follow-up, complete blood count, urinalysis, serum AFP level, liver and kidney function test, and blood concentration of FK506 were recorded. Chest and abdominal computed tomography was implemented at 3 months, 6 months, 12 months, and annually thereafter. Other radiological examinations such as radionuclide bone scan, magnetic resonance imaging (MRI) and positron emission tomography (PET) were obtained when local recurrence or distant metastasis was suspected.

The DFS was defined as the period between the day of LT and the day of HCC recurrence confirmed by imaging, while the OS was defined as the duration from LT to death of patients for any reason or to end of follow-up. Common terminology criteria for adverse events version 5.0 (CTCAE V5.0) was used to assess the AE during oral administration of lenvatinib. The FK506 dosage and blood concentration of each patients in the first six months after liver LT was recorded for evaluate the influence of lenvatinib on the immunosuppressive therapy.

Mean and standard deviations were used for descriptive statistics. The patient characteristics in each group were compared by one-way ANOVA and chi-square tests. Repeated measures analysis of variances was used for comparing the difference of FK506 dosage and blood concentration between two groups. The OS and DFS were statistically analyzed by the Kaplan-Meier method. Statistical significance was set at P<0.05. All statistical analyses were performed using SPSS software Version 10.0.

Being tested
Lenvatinib
Keywords
Hepatocellular Carcinoma, liver transplantation, lenvatinib, adjuvant therapy
Medical subject headings
Carcinoma, Hepatocellular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LenvatinibDrug

    The patients in lenvatinib group received oral lenvatinib (Eisai, Japan) 12 mg/day (for bodyweight (BW) ≥60 kg) or 8 mg/day (for BW <60 kg) in 28-day cycles until HCC recurrence or serious adverse events (SAEs) or voluntary withdrawal. Dose interruptions followed by reductions for lenvatinib-related toxicities (to 8 mg and 4 mg/day, or 4 mg every other day) were permitted. All 14 patients took lenvatinib for more than 3 cycles.

Study groups in NCT04415567
Study groupRoleWhat they receive
lenvatinibhigh-risk patients with HBV-related HCC who took lenvatinib as adjuvant therapy after liver transplantation
Receives: Drug: Lenvatinib
controlhigh-risk patients with HBV-related HCC who received routine treatment and follow-up after liver transplantation

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Disease-free survival (DFS)

    The disease-free survival (DFS) was defined as the period between the day of LT and the day of HCC recurrence confirmed by imaging.

    Measured: up to 3 years

Secondary outcomes (1)
  1. Overall survival (OS)

    The overall survival (OS) was defined as the period between the day of LT and the day of the participants' death or the termination of the study in 3 years after LT.

    Measured: up to 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Jun 2020
  2. Study start1 Jun 2018
  3. Primary completion31 Mar 2020
  4. Study completion31 Mar 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Case-control
Time perspective
Retrospective
Enrolment
23 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04415567
Sponsor's protocol ID
XH-20-010
Status last verified
Jun 2020
First submitted
22 May 2020
Last updated
4 Jun 2020
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: The IPDs to be shared include study protocol, statistical analysis methods, informed consent form and clinical study report.

Publications

  • Kudo M, Finn RS, Qin S, Han KH, Ikeda K, Piscaglia F, Baron A, Park JW, Han G, Jassem J, Blanc JF, Vogel A, Komov D, Evans TRJ, Lopez C, Dutcus C, Guo M, Saito K, Kraljevic S, Tamai T, Ren M, Cheng AL. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet. 2018 Mar 24;391(10126):1163-1173. doi: 10.1016/S0140-6736(18)30207-1.

    PubMed 29433850
  • Briggs A, Daniele B, Dick K, Evans TRJ, Galle PR, Hubner RA, Lopez C, Siebert U, Tremblay G. Covariate-adjusted analysis of the Phase 3 REFLECT study of lenvatinib versus sorafenib in the treatment of unresectable hepatocellular carcinoma. Br J Cancer. 2020 Jun;122(12):1754-1759. doi: 10.1038/s41416-020-0817-7. Epub 2020 Apr 8.

    PubMed 32265508
  • Siegel AB, El-Khoueiry AB, Finn RS, Guthrie KA, Goyal A, Venook AP, Blanke CD, Verna EC, Dove L, Emond J, Kato T, Samstein B, Busuttil R, Remotti H, Coffey A, Brown RS Jr. Phase I trial of sorafenib following liver transplantation in patients with high-risk hepatocellular carcinoma. Liver Cancer. 2015 Mar;4(2):115-25. doi: 10.1159/000367734.

    PubMed 26020033
  • Teng CL, Hwang WL, Chen YJ, Chang KH, Cheng SB. Sorafenib for hepatocellular carcinoma patients beyond Milan criteria after orthotopic liver transplantation: a case control study. World J Surg Oncol. 2012 Feb 17;10:41. doi: 10.1186/1477-7819-10-41.

    PubMed 22339891

Questions about this trial

What is this clinical trial studying?

An observational study of Hepatocellular Carcinoma, run by Jinyang Gu at 1 site in China.

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 4 inclusion and 6 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 4 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. 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.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Disease-free survival (DFS) (time frame: up to 3 years). 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 NCT04415567, which also lists 4 linked publications.

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 4 Jun 2020.

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