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

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

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.

Study Overview

• Status: Unknown
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: Lenvatinib; Drug: Immunosuppressive regimen; Drug: Placebo

Detailed 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).

• Study Type: Interventional
• Enrollment (Anticipated): 108
• Phase: Phase 2; Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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. ⑥Immunosuppressive regimen consists of calcineurin inhibitor, mycophenolate mofetil and sirolimus.

          ⑦No history of surgical resection of liver tumors and targeted drug therapy before liver transplantation.

          ⑧Good 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.

          ⑧For fertile female patients, the serum/urine pregnancy test should be negative within 7 days before treatment.

          ⑨All male and female participants must take reliable contraceptive measures during the trial and within four weeks after the end of the trial.

          ⑩The participants have the capability of oral medication.

          ⑾The 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.

              ⑧Severe clinical active infections (> NCI-CTCAE version 3.0).

              ⑨Epilepsy patients requires medication (e.g. steroids or antiepileptic drugs).

              ⑩Patients with kidney diseases requires renal dialysis.

              ⑾Drug abuse, medical symptoms, mental illness or social status that may interfere with participants'participation in research or evaluation of research results.

              ⑿Patients who could not swallow oral drugs, such as those with severe upper gastrointestinal obstruction and need gastric tube feeding.

              ⒀Other anti-angiogenesis therapies, surgery, TACE, local therapy and systemic chemotherapy were given before the treatment after liver transplantation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: lenvatinib group; Participants are given the same anti-rejection therapy as the control group after liver transplantation. 1-2 months after liver transplantation, participants are given lenvatinib with an initial dose of 8 mgor 12 mg orally once a day. The initial dose was 8 mgor 12 mg orally once a day.	Drug: Lenvatinib; Patients in the lenvatinib group are given lenvatinib within 1-2 months after operation; Other Names: E7080; Drug: Immunosuppressive regimen; Immunosuppressive regimen consisting of calcineurin inhibitor, mycophenolate mofetil, sirolimus or ivermus
Placebo Comparator: Placebo group; Immunosuppressive regimen consisting of calcineurin inhibitor, mycophenolate mofetil, sirolimus or ivermus	Drug: Immunosuppressive regimen; Immunosuppressive regimen consisting of calcineurin inhibitor, mycophenolate mofetil, sirolimus or ivermus; Drug: Placebo; Sugar pill manufactured to mimic Lenvatinib 10mg tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor free survival rate	The 1, 3, 5-year of tumor free survival rate	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival rate	The 1, 3, 5-year of overall survival rate	5 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: RenJi Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): November 1, 2019
• Primary Completion (Anticipated): September 1, 2022
• Study Completion (Anticipated): September 1, 2022

Study Registration Dates

• First Submitted: November 8, 2019
• First Submitted That Met QC Criteria: November 17, 2019
• First Posted (Actual): November 19, 2019

Study Record Updates

• Last Update Posted (Actual): November 19, 2019
• Last Update Submitted That Met QC Criteria: November 17, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: Hepatocellular Carcinoma; Liver Transplantation
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Immunologic Factors; Protein Kinase Inhibitors; Lenvatinib; Immunosuppressive Agents
• Other Study ID Numbers: KY2019059

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes