Adjuvant Therapy for High-risk Hepatocellular Carcinoma Post Liver Transplantation

NCT06041490 | Not Yet Recruiting Phase 2

• 1 other identifier: K4001
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 1

Brief Summary

1. 1.Explore the impact of postoperative administration of multi-kinase inhibitors (including sorafenib, lenvatinib, and regorafenib) in conjunction with bevacizumab on post-transplant recurrence, overall survival, and drug safety in liver transplant recipients at high risk of recurrence in hepatocellular carcinoma.
2. 2.The primary objective of this study is to evaluate the efficacy of multi-kinase inhibitors in combination with bevacizumab as adjuvant therapy in liver transplant recipients with hepatocellular carcinoma who present high-risk factors for recurrence, based on the one-year recurrence-free survival rate (1-year RFS rate).
3. 3.The secondary objectives of this study are to assess the effectiveness and safety of multi-kinase inhibitors in combination with bevacizumab as adjuvant therapy in liver transplant recipients with hepatocellular carcinoma who present high-risk factors for recurrence, based on the following parameters: Recurrence-free survival (RFS) duration, Overall survival (OS), Two-year and three-year RFS rates, Graft survival, Quality of life evaluation (QoL), Incidence of adverse events and serious adverse events.

Conditions

Liver Transplant; Complications; Hepatocarcinoma; Recurrent Osteosarcoma; High-Risk Cancer

Keywords

Hepatocarcinoma; Liver Transplant; Recurrence; High-Risk; multikinase inhibitor; bevacizumab

Outcome Measures

Primary Outcomes (1)

• EFFICACY: One-year recurrence-free survival rate (1-year RFS rate)

  One-year recurrence-free survival rate (1-year RFS rate): The one-year recurrence-free survival rate represents the proportion of patients, within a specified study population, who remain free from disease recurrence for at least one year following a designated treatment or intervention.

  Baseline up to 12 months

Secondary Outcomes (6)

• EFFICACY: Recurrence-free survival (RFS) duration

  Baseline up to approximately 12 months

• EFFICACY: Overall survival (OS)

  Baseline up to approximately 3 years

• EFFICACY: Two-year and three-year RFS rates

  Baseline up to approximately 2-3 years

• EFFICACY and SAFETY: Graft survival

  Baseline up to approximately 3 years

• QUALITY OF LIFE：Quality of life evaluation

  Baseline up to approximately 3 years

Study Arms (2)

multi-kinase inhibitors in combination with bevacizumab

EXPERIMENTAL

TKI (Sorafenib 400mg, bid, po or Lenvatinib 8mg, qd, po if bodyweight less than 60 kg,12mg, qd, po if bodyweight more than 60kg or Donafenib：200mg, bid, po) + bevacizumab：7.5mg/kg, infusion, Q3w

Drug: multi-kinase inhibitors in combination with bevacizumab

Without adjuvant therapy

NO INTERVENTION

No intervention.

Interventions

multi-kinase inhibitors in combination with bevacizumab DRUG

The eligible participants will start taking multi-kinase inhibitors between 4-8 weeks after liver transplantation. The choice of the specific multi-kinase inhibitor, including sorafenib, lenvatinib, or regorafenib, will be determined by the researchers based on factors such as the participant's tumor characteristics, liver function, physical condition, risk of side effects, economic status, and personal preference. The specific dosage and administration details can be found in the table provided. The maximum duration of multi-kinase inhibitor treatment will be 12 months or until any of the following conditions occur, whichever comes first: 1) The participant experiences intolerable toxic reactions that do not alleviate with dose adjustments, or 2) The participant has documented disease recurrence confirmed through imaging or withdraws from the study for other reasons.

multi-kinase inhibitors in combination with bevacizumab

Eligibility Criteria

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

You may qualify if:

• Voluntary enrollment, accompanied by the signing of a written informed consent form, is a prerequisite for participation in this study. This ensures that participants enter the study based on their own decision and understanding of the research objectives, procedures, and potential risks.
• The study includes individuals aged between 18 and 75 years, inclusive, without any gender restrictions. This broad age range and gender inclusivity allow for a diverse representation of participants, facilitating a comprehensive understanding of the study outcomes across different demographic profiles.
• Participants must have a confirmed pathological diagnosis of hepatocellular carcinoma (HCC) and meet at least one of the following criteria:
• a) Pre-operative imaging or post-operative pathological confirmation of exceeding the Milan criteria.
• b) Presence of major vascular invasion. c) Post-operative pathological confirmation of the presence of microvascular invasion (MVI).
• d) Pre-operative imaging or post-operative pathological confirmation of the presence of satellite nodules.
• e) Recurrence of HCC after liver resection and subsequent liver transplantation.
• Participants should have an anticipated life expectancy of more than 3 months.
• Participants should not have received systemic anti-tumor treatment prior to liver transplantation, with the exception of pre-operative transarterial chemoembolization (TACE), traditional Chinese medicine, and interferon treatment.
• Participants should have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1, indicating good functional status.
• Participants' liver function, as assessed by the Child-Pugh score, should be classified as Grade A, indicating well-preserved liver function.
• HBsAg-positive patients should receive continuous antiviral therapy post-transplantation, using first-line antiviral drugs such as entecavir, tenofovir, or tenofovir alafenamide.
• Participants should have adequate hematological and organ function, based on the laboratory test results obtained within 14 days before the initiation of the study treatment, as follows:
• Laboratory tests (unless otherwise specified, no blood transfusion or use of G-CSF within 14 days prior to screening):
• Hemoglobin ≥ 90 g/L.

You may not qualify if:

• According to the information provided, the following patients are not eligible for participation in this study.
• Patients with a previous histological/cytological diagnosis of fibrolamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, cholangiocarcinoma, or other similar components.
• Patients with a history of malignancies other than hepatocellular carcinoma, unless they meet the following criteria:
• Patients who have undergone potentially curative treatment and have no evidence of the disease within the past 5 years.
• Patients who have successfully undergone resection of basal cell carcinoma, squamous cell carcinoma, superficial bladder cancer, cervical carcinoma in situ, or other in situ carcinomas; or patients who have been treated for superficial bladder cancer, have undergone surgical treatment, and have prostate-specific antigen (PSA) tumor markers within the normal range.
• Patients who are concurrently taking medications that may prolong the QTc interval and/or induce torsades de pointes (Tdp) or medications that affect drug metabolism.
• Patients with a known or suspected history of allergies to sorafenib, lenvatinib, donafenib, or similar drugs.
• Patients with active bleeding or coagulation abnormalities, bleeding tendencies, or those undergoing thrombolysis, anticoagulant therapy, or antiplatelet therapy.
• Patients who have experienced thrombosis or thromboembolic events within the past 6 months, such as stroke and/or transient ischemic attack, deep vein thrombosis, pulmonary embolism, etc.
• Patients with clinically significant cardiovascular diseases, including but not limited to acute myocardial infarction within the past 6 months, severe/unstable angina or coronary artery bypass grafting, congestive heart failure (NYHA class \>2), poorly controlled or requiring pacemaker therapy for arrhythmias, poorly controlled hypertension (systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg) despite medication.
• Other significant clinical and laboratory abnormalities that the investigator deems to impact safety assessment, such as uncontrolled diabetes, chronic kidney disease, peripheral neuropathy of grade II or higher (CTCAE V5.0), thyroid dysfunction, etc.
• Active or poorly controlled severe infections, including:
• HIV-positive (HIV1/2 antibody).
• Active hepatitis B (positive for HBsAg or HBV DNA\>2000 IU/ml and abnormal liver function).
• Active hepatitis C (positive for HCV antibody or HCV RNA≥103 copies/ml and abnormal liver function).

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead

Study Sites (1)

Chinese Academy of Medical Sciences & Peking Union Medical College Hospital (CAMS&PUMCH)

Beijing, Beijing Municipality, 100730, China

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Osteosarcoma; Recurrence

Interventions

Bevacizumab

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; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Sarcoma; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• haitao zhao

  Peking Union Medical College Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

haitao zhao

CONTACT

01069156874; zhaoht@pumch.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 30, 2023
• First Posted: September 18, 2023
• Study Start: September 1, 2023
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): January 1, 2027
• Last Updated: September 18, 2023

Record last verified: 2023-08

Locations

CN (1)