Lenvatinib Following Liver Transplantation in Patients With High-Risk Hepatocellular Carcinoma

Hepatocellular Carcinoma Clinical Trial

Official title:

A Randomized Controlled Study of Lenvatinib Following Liver Transplantation in Patients With High-Risk Hepatocellular Carcinoma

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04168944
• Other study ID #: KY2019059
• Status: Not yet recruiting
• Phase: Phase 2/Phase 3
• Start date: November 2019
• Est. completion date: September 2022

Study information

• Verified date: November 2019
• Source: RenJi Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of this study is to observe the efficacy and safety of lenvatinib in preventing high-risk recurrence of hepatocellular carcinoma patients after liver transplantation.The cases are from patients with hepatocellular carcinoma who underwent liver transplantation in the liver surgery department of Shanghai Renji Hospital. Patients enrolled in the study were randomly allocated in the lenvatinib group (54 patients) and the control group (54 patients) after stable condition.

Description:

The research is an open, randomized, single-center study. Patients with high-risk recurrence of hepatocellular carcinoma who underwent liver transplantation are included according to the criteria of admission. After operation, the regimen of calcineurin inhibitors, mycophenolate mofetil, sirolimus or everolimus with glucocorticoids removed at an early stage are used. Patients enrolled in the study were randomly allocated in the lenvatinib group (54 patients) and the control group (54 patients) after stable condition. Patients in the control group are given supportive treatment and regular follow-up. Patients in the lenvatinib group are given lenvatinib within 1-2 months after operation (dose: body weight < 60 kg: 8 mg/day, body weight ≥ 60 kg 12 mg/day). The baseline data of patients are collected before allocation. Serum and imaging examination are checked regularly every month to monitor the recurrence of hepatocellular carcinoma and the side effects of lenvatinib. The efficacy and safety of lenvatinib in patients of high-risk hepatocellular carcinoma are observed, and the clinicopathological factors affecting the efficacy of lenvatinib are analyzed. When side effects of lenvatinib occur, the dosage can be reduced according to the patients' condition until discontinuation. When tumor recurrence occurs, a multidisciplinary team will draw up specific treatment plans according to the patients' condition, including surgical resection, interventional therapy, radiofrequency therapy, radiotherapy and targeted therapy (Patients in the control group can add lenvatinib, and patients in the lenvatinib group can decide whether to continue using it according to the patients' condition).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 108
• Est. completion date: September 2022
• Est. primary completion date: September 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Patients at high risk of recurrence of hepatocellular carcinoma after liver transplantation: extended Milan criteria, without vascular invasion (except for microvascular invasion suggested by pathology after operation)

• Male or female patients aged 18 to 75.

• ECOG physical condition was 0-2 points.

• Child-Pugh A grade of liver function.

• Targeted therapy is acceptable within 1-2 months after liver transplantation. ?Immunosuppressive regimen consists of calcineurin inhibitor, mycophenolate mofetil and sirolimus.

?No history of surgical resection of liver tumors and targeted drug therapy before liver transplantation.

?Good liver, kidney and bone marrow function: serum albumin > 28g/L, total bilirubin = 3 mg/dL (51.3 umol/l), ALT and AST = 5 times the upper limit of normal range; serum creatinine = 1.5 times the upper limit of normal range; hemoglobin > 90 g/L, neutrophil count (ANC) > 1.5 * 10 ^ 9/L, platelet count > 60 * 10 ^ 9/L; PT-INR < 2.3, or PT within 6 seconds over normal upper limit.

?For fertile female patients, the serum/urine pregnancy test should be negative within 7 days before treatment.

?All male and female participants must take reliable contraceptive measures during the trial and within four weeks after the end of the trial.

?The participants have the capability of oral medication.

?The participants must sign the consent form.

Exclusion Criteria:

• Life expectancy is less than 3 months

• The recurrence and metastasis of hepatocellular carcinoma are highly suspected.

• Patients are with other malignant tumors simultaneously.

• Patients are anaphylaxis to the inactive ingredients of lenvatinib or drugs.

• Pregnant or lactating women (Female participants need pregnancy test within 7 days before treatment).

• Preoperative history of severe cardiovascular disease:

congestive heart failure > NYHA grade 2; active coronary heart disease (myocardial infarction occurred within 6 months before entry into the study); severe arrhythmia requiring antiarrhythmic treatment (allowable use of beta-blockers or digoxin); uncontrolled hypertension.

• History of HIV infection.

?Severe clinical active infections (> NCI-CTCAE version 3.0).

?Epilepsy patients requires medication (e.g. steroids or antiepileptic drugs).

?Patients with kidney diseases requires renal dialysis.

?Drug abuse, medical symptoms, mental illness or social status that may interfere with participants'participation in research or evaluation of research results.

?Patients who could not swallow oral drugs, such as those with severe upper gastrointestinal obstruction and need gastric tube feeding.

?Other anti-angiogenesis therapies, surgery, TACE, local therapy and systemic chemotherapy were given before the treatment after liver transplantation.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

Drug:
• Lenvatinib
Patients in the lenvatinib group are given lenvatinib within 1-2 months after operation
• Placebo
Sugar pill manufactured to mimic Lenvatinib 10mg tablet
• Immunosuppressive regimen
Immunosuppressive regimen consisting of calcineurin inhibitor, mycophenolate mofetil, sirolimus or ivermus

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
RenJi Hospital

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	the side effects	The side effects during treatment were recorded. At the same time, patients status will be scored according to ECOG PS score. Acute or subacute toxicity is classified as level of 0-4, 0 as non-response, 1 as mild, 2 as moderate, 3 as severe and 4 as life-threatening. The severity of adverse events was judged, reported and handled according to GCP requirements of clinical trials.	5 years
Primary	Tumor free survival rate	The 1, 3, 5-year of tumor free survival rate	5 years
Secondary	Overall survival rate	The 1, 3, 5-year of overall survival rate	5 years