Clinical Study on the Effectiveness and Safety of Lenvatinib As Adjuvant Treatment for Patients with High-risk Recurrence of Hepatocellular Carcinoma After Surgery

NCT06762782 | Recruiting Phase 2 DMC

• 1 other identifier: 2024-SR-708
• Study Type: interventional
• Target: 276
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a prospective, randomized, controlled, open, phase II, multicenter clinical study, which aims to evaluate the efficacy and safety of lenvatinib for adjuvant treatment of high-risk recurrent liver cancer after radical surgery. This study is divided into 3 stages: screening period (screening period 28 days), treatment period (up to 12 months, or until any of the following occurs, whichever occurs first: ① The subject has an intolerable toxic reaction and is still not relieved after dose adjustment; ② The subject's first imaging confirmed disease recurrence or withdrew from the study for other reasons), and follow-up period (12 months after the end of treatment). Dosage regimen: Eligible subjects were randomly assigned to the experimental group or the control group in a 2:1 ratio, with surgical method (radical surgery vs ablation) as the stratification factor. The experimental group received lenvatinib treatment, and the control group received best supportive care

Conditions

Hepatocellular Carcinoma (HCC); Adjuvant Therapy in Patients with Hepatocellular Carcinoma (HCC) At High Risk of Recurrence After Curative Resection or Ablation

Keywords

lenvatinib；adjuvant therapy；hepatocellular carcinoma

Outcome Measures

Primary Outcomes (1)

• 1-year cumulative recurrence-free patient percentage

  Proportion of patients with high-risk recurrent hepatocellular carcinoma who are free of tumor recurrence within one year after curative surgery.

  The patient started taking lenvatinib after radical surgery for hepatocellular carcinoma and continued treatment for up to 1 year.

Secondary Outcomes (4)

• Recurrence Free Survival

  The patient started taking lenvatinib after radical surgery for hepatocellular carcinoma and continued treatment for up to 3 years.

• Overall Survival

  The time span from the date of surgery to the date of the patient's last follow-up visit or death, assessed up to 3 years.

• Time To Recurrence

  The time span from the date of radical liver resection to the date of first documented tumor recurrence, assessed up to 3 years.

• Diachronic changes in quality of life scores based on FACT-Hep scale

  From enrollment date to database deadline, assessed up to 3 years.

Study Arms (2)

Treatment group

EXPERIMENTAL

According to the instructions, lenvatinib 8mg (weight ≤ 60Kg) or 12mg (weight ≥ 60Kg) was given orally once a day, and active monitoring was performed.

Drug: Postoperative adjuvant lenvatinib

Control group

OTHER

After surgery, the best supportive care was given, and active monitoring was performed.

Other: Supportive care measures

Interventions

Postoperative adjuvant lenvatinib DRUG

Follow the instructions and take lenvatinib 8 mg (body weight ≤ 60Kg) or 12 mg (body weight ≥ 60Kg) orally once a day.

Treatment group

Supportive care measures OTHER

Adjuvant treatments such as antiviral, TACE, HAIC, radiotherapy, and systemic antitumor therapy can be used

Control group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Certainly, here is the translation of the provided text into English:
• Age between 18 to 80 years old, gender not limited;
• Received radical treatment surgery for liver cancer within 4 to 8 weeks prior to enrollment, and meet the following criteria: (1) Intraoperative judgment criteria: ① No gross tumor thrombus in the hepatic vein, portal vein, bile duct, and inferior vena cava; ② No invasion of adjacent organs, no hepatic hilum lymph nodes or distant metastasis; ③ The liver resection margin is ≥1cm from the tumor border; if the margin is less than 1cm, the histological examination of the resected liver surface shows no residual tumor cells, i.e., negative resection margin. (2) Postoperative judgment criteria: ① Ultrasound, computed tomography(CT), magnetic resonance imaging(MRI) examinations (at least two of these) are performed within 1 to 2 months after surgery, with no residual or recurrent tumor lesions in radical resection cases, and no active tumor lesions in radical ablation cases; ② If serum alpha-fetoprotein(AFP), des-gamma-carboxy prothrombin(DCP), and a combination of 7 Micro ribonucleic acid(microRNAs) and other tumor markers were elevated before surgery, then quantitative measurement of tumor markers is required 8 weeks after surgery, and their levels drop to the normal range; if serum alpha-fetoprotein(AFP) does not return to normal within 8 weeks after surgery , will not be included.
• Postoperative pathological examination confirms hepatocellular carcinoma(HCC), and all tumor nodules are completely removed with negative resection margins.
• Imaging examinations ≥4 weeks after surgery confirm no recurrence or metastasis.
• Expected survival \>3 months;
• hepatitis B virus(HBV) deoxyribonucleic acid(DNA) \<10\^4 copies/ml (2000 IU/ml), if hepatitis B virus(HBV) deoxyribonucleic acid(DNA) ≥10\^4 copies/ml, antiviral treatment should be initiated first until hepatitis B virus(HBV) deoxyribonucleic acid(DNA) is reduced to below 10\^4 copies/ml before entering the study, and continue to take antiviral medication and monitor liver function and hepatitis B virus(HBV) load.
• At least one of the following high recurrence risk factors exists:
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• Tumor diameter \>5cm
• Multiple lesions (\>3)
• Pathology indicates MVI positivity
• Edmondson III-IV grade
• Persistently abnormal alpha-fetoprotein 8. No history of other tumors, and no antitumor treatment before surgery; 9. Eastern Cooperative Oncology Group(ECOG) score: 0-1. 10. Major organ functions are normal, i.e., meeting the following criteria:
• Hematology examination (within 14 days before screening, without blood transfusion or use of granulocyte colony stimulating factor(G-CSF)):

You may not qualify if:

• Here is the translation of the provided text into English:
• Pathologically diagnosed as a mixed type of hepatocellular carcinoma-intrahepatic cholangiocarcinoma (HCC-ICC).
• Positive surgical margins or tumor rupture.
• Reoperation for recurrent liver cancer.
• History of other malignancies within 5 years, unless the patient has undergone potentially curative treatment and has no evidence of the disease for 5 years, except for patients who have successfully undergone resection surgery for skin basal cell carcinoma, skin squamous cell carcinoma, superficial bladder cancer, cervical carcinoma in situ, or other carcinoma in situ (the 5-year requirement does not apply).
• Past or current congenital or acquired immunodeficiency diseases.
• Patients who have undergone allogeneic transplantation.
• Insufficient biopsy and/or surgical samples are unavailable.
• Pregnant and breastfeeding patients.
• Received targeted drug therapy such as sorafenib, lenvatinib, regorafenib, or immunomodulatory therapy such as anti-PD-1, anti-PD-L1, anti-CTLA-4 before surgery.
• Unable to provide informed consent (due to language, intellectual capacity, etc.).
• Active bleeding or coagulation abnormalities, with a tendency to bleed or currently undergoing thrombolytic, anticoagulant, or antiplatelet therapy.
• History of gastrointestinal bleeding within the past 4 weeks or a clear tendency towards gastrointestinal bleeding (e.g., known active local ulcer lesions, fecal occult blood ++ or more, if persistent fecal occult blood +, gastroscopy should be performed), or other conditions that may cause gastrointestinal bleeding as determined by the investigator (e.g., severe gastric fundus/esophageal varices).
• Significant clinically meaningful cardiovascular diseases, including but not limited to acute myocardial infarction, severe/unstable angina, or coronary artery bypass grafting within the past 6 months, congestive heart failure (New York Heart Association NYHA class \>2), arrhythmias that are poorly controlled or require pacemaker treatment, uncontrolled hypertension with medication (systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg).
• Allergy to chemotherapy drugs or contraindications to surgery.

Sponsors & Collaborators

• The First Affiliated Hospital with Nanjing Medical University: lead
• The First People's Hospital of Changzhou: collaborator
• Affiliated Hospital of Nantong University: collaborator
• Suzhou Municipal Hospital: collaborator
• Zhongda Hospital: collaborator
• Northern Jiangsu People's Hospital: collaborator
• The First People's Hospital of Lianyungang: collaborator
• The Affiliated Hospital of Xuzhou Medical University: collaborator
• Xuzhou Central Hospital: collaborator
• Huai'an First People's Hospital: collaborator
• Jiangsu Taizhou People's Hospital: collaborator

Study Sites (1)

The First Affiliated Hospital of Nanjing Medical University

Nanjing, Jiangsu, 210029, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular

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

Central Study Contacts

Haomin Zhou

CONTACT

86-13645165073; hmzhou@njmu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Eligible subjects were randomly assigned to the experimental group or the control group at a ratio of 2:1, with surgical method (radical surgery vs ablation) as the stratification factor. Treatment group: According to the instructions, lenvatinib 8mg (weight ≤ 60Kg) or 12mg (weight ≥ 60Kg) was given orally once a day, and active monitoring was performed. Control group: After surgery, the best supportive care was given, and active monitoring was performed.

Study Record Dates

• First Submitted: December 22, 2024
• First Posted: January 8, 2025
• Study Start: February 1, 2025
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2027
• Last Updated: January 8, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)