Clinical trial NCT06409637: FOLFOX Plus Lenvatinib Adjuvant Therapy for Hepatocellular Carcinoma Post-Liver Transplantation
Official title: A Prospective, Single-arm Clinical Study of FOLFOX Combined With Lenvatinib as Adjuvant Chemotherapy to Prevent Tumor Recurrence After Liver Transplantation for Hepatocellular Carcinoma Beyond Milan Criteria
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Liver Cancer
Liver Transplant
Lead sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Sponsor class: OTHER
First posted: 2024-05-10
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: Liver transplantation not only removes the liver tumor (seed) but also eliminates the underlying diseased liver (soil), making it an essential therapeutic approach for hepatocellular carcinoma (HCC). However, the tumor recurrence post-liver transplantation significantly jeopardizing the long-term survival of transplant recipients. Given the scarcity of donor livers, exploring effective measures to prevent tumor recurrence after liver transplantation holds significant clinical and societal value. Currently, there is no consensus on adjuvant therapy for preventing tumor recurrence post-liver transplantation for HCC, and the quantity and quality of studies on systemic chemotherapy are limited. In recent years, administration of the FOLFOX regimen combined with lenvatinib has been widely used in the treatment of advanced HCC, showing remarkable efficacy. The aim of this study is to investigate the efficacy and safety of adjuvant chemotherapy with FOLFOX combined with lenvatinib in preventing tumor recurrence after liver transplantation for HCC beyond Milan criteria.


Eligibility criteria: Inclusion Criteria:

1. Age between 18 and 75 years inclusive.
2. Histologically confirmed hepatocellular carcinoma without other non-hepatocellular carcinoma components.
3. ECOG performance status 0-1.
4. Child-Pugh class A liver function.
5. Eligible for chemotherapy and targeted therapy within 1-2 months after liver transplantation.
6. Immunosuppressive regimen including calcineurin inhibitors, mycophenolate mofetil, and sirolimus.
7. Adequate liver, kidney, and bone marrow function: serum albumin \>28g/L, total bilirubin ≤3mg/dL (51.3 umol/l), ALT and AST ≤5 times the upper limit of normal; serum creatinine ≤1.5 times the upper limit of normal; hemoglobin \>90g/L, absolute neutrophil count (ANC) \>1.5×10\^9/L, platelet count \>60×10\^9/L; PT-INR \<1.5 or PT within normal limits +6 seconds.
8. Negative serum/urine pregnancy test within 7 days prior to treatment initiation for fertile women.
9. Reliable contraception must be used by all male and female participants during the trial and for six months after its completion.
10. Ability to take oral medications.
11. Participants must provide written informed consent.

Exclusion Criteria:

1. Life expectancy less than 6 months.
2. High suspicion of hepatocellular carcinoma recurrence and metastasis.
3. Concurrent malignancies.
4. Allergy to lenvatinib or chemotherapy drugs.
5. Pregnant or lactating women (female participants must undergo pregnancy testing within 7 days prior to treatment).
6. History of severe cardiovascular diseases: congestive heart failure \>NYHA class 2; active coronary artery disease (myocardial infarction within 6 months prior to enrollment); severe arrhythmias requiring antiarrhythmic therapy (β-blockers or digoxin permitted); uncontrolled hypertension.
7. History of HIV infection.
8. Severe active clinical infections.
9. Patients requiring medication for epilepsy (e.g., steroids or antiepileptic drugs).
10. Patients with kidney diseases requiring dialysis.
11. Drug abuse, medical conditions, psychiatric illnesses, or social status that may interfere with the participant's participation in the study or evaluation of study results.
12. Patients unable to swallow oral medications, such as those with severe upper gastrointestinal obstruction requiring gastric tube feeding.
13. Previous treatment with other anti-angiogenic therapies, surgery, TACE, local therapy, systemic chemotherapy, immunotherapy, etc., before liver transplantation.
14. Clear evidence of main portal vein/hepatic vein tumor thrombus or inferior vena cava tumor thrombus.
15. Clear evidence of lymph node metastasis.

Primary outcomes:
measure: 2-year recurrence-free survival
timeFrame: 2 years
Secondary outcomes:
measure: 2-year overall survival
timeFrame: 2 years
measure: Adverse event and validation of adverse event incidence
timeFrame: 2 years
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Organ Transplantation Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University,
state: Guangdong
Study officials:
affiliation: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
name: Leibo Xu, PhD
role: PRINCIPAL_INVESTIGATOR
References: