Immunotherapy for Liver Cancer Patients Before Transplantation

A Prospective, Single-arm Study of Downstaging Protocol Containing Immunotherapy for HCC Beyond the Milan Criteria Before Liver Transplantation

This study is testing if a new immunotherapy treatment can help liver cancer patients shrink their tumors enough to qualify for a liver transplant.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 59 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University (other)
• Drugs / interventions: immunotherapy, tislelizumab, pembrolizumab, nivolumab, lenvatinib
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT05475613 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the efficacy and safety of a downstaging protocol that includes immunotherapy for patients with hepatocellular carcinoma (HCC) who exceed the Milan criteria for liver transplantation. Eligible participants will receive anti-PD-1 inhibitors and other combination therapies over a series of treatment cycles. The study will assess whether these treatments can successfully downstage the cancer to meet the criteria for transplantation. Patients who do not achieve the downstaging criteria after the treatment will be withdrawn from the study.

Who should consider this trial

Good fit: Ideal candidates are patients with hepatocellular carcinoma beyond the Milan criteria without extrahepatic metastases or lymph node involvement.

Not a fit: Patients with extrahepatic metastases or those who do not meet the inclusion criteria will not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could expand the eligibility for liver transplantation in patients with advanced HCC, potentially improving survival rates.

How similar studies have performed: Previous studies have shown promising results with downstaging therapies, but this specific approach combining immunotherapy is novel.

Eligibility criteria

Inclusion Criteria:

1. Written informed consent must be obtained prior to any screening procedures. Willing and able to comply with scheduled visits, treatment plan and laboratory tests.
2. Patients must have pathologically or cytologically or by radiological criteria proven hepatocellular carcinoma based on the AASLD practice guidelines
3. Patients with HCC must be beyond Milan criteria without extrahepatic metastases or lymph node metastases:

   3.1 Patients without previous treatment: Barcelona clinic liver cancer B-C (China liver cancer stage IIb-IIIa) HCC with or without portal vein tumor thrombus (PVTT 1-3 according to Japanese Vp classification).

   3.2 Patients with late recurrent HCC: The recurrent HCC must be identified no less than 2 years after primary curative treatment (Resection or Radiofrequency, et al), and the recurrent lesions must be localized in the liver and beyond Milan criteria.

   3.3 Patients with early recurrent HCC: The recurrent HCC must be identified within 2 years after primary curative treatment (R0 resection or radiofrequency, et al), and the primary tumor must be within Milan criteria, and the accumulating tumor burden(Primary tumor plus recurrent tumor) must be beyond Milan criteria.
4. Child-Pugh score≤7, with no encephalopathy. Ascites that diuretics can control are permitted in this study.
5. Eastern Cooperative Oncology Group (ECOG) Scale for Assessment of Patient Performance Status (PS score) ≤ 2; KPS score ≥60.
6. Have not received any immunotherapies 6 months before enrollment.
7. Adequate bone marrow, liver, and renal function.
8. The estimated survival before liver transplantation must be more than 12 weeks (Based on the Model for end-stage liver disease, MELD).
9. No other lethal malignancy outside the liver in the past 5 years, such as leukemia, lung cancer, melanoma, etc.
10. Patients with a history of hypertension should be well-controlled (\< 140/90 mmHg) on a regimen of anti-hypertensive therapy.
11. Both men and women enrolled in this trial must use adequate barrier birth control measures during the trial and 6 months after the completion of the trial.
12. Patients voluntarily joined the study and signed informed consent with good compliance and follow-up.

Exclusion Criteria

Participants who meet any of the following criteria are not eligible for this study:

1. Histologically/cytologically confirmed cholangiocellular carcinoma, mixed-type liver cancer, or other rare types of liver cancer;
2. Recurrent liver cancer with inadequate initial treatment (i.e., no complete remission or R0 resection);
3. Presence of uncontrollable systemic infections, alcoholism or drug abuse, organic diseases of the heart, lungs, or brain, uncontrolled psychiatric disorders, severe mental illnesses, HIV infection, active tuberculosis, etc.;
4. Presence of severe portal hypertension with a high bleeding risk as assessed by the investigator;
5. History of bleeding events due to portal hypertension in the past 6 months;
6. History of any life-threatening event in the past 6 months, including but not limited to acute myocardial infarction, unstable angina, congestive heart failure, cerebrovascular accidents, pulmonary embolism, major bleeding from other sites, etc.;
7. Severe splenomegaly or splenomegaly-induced neutropenia (ANC \< 1.5 × 10⁹/L) or thrombocytopenia (platelet count \< 50 × 10⁹/L);
8. History of grade III hepatic encephalopathy or clinical symptoms requiring long-term drainage of pleural effusion, ascites, pericardial effusion, etc.;
9. Uncontrolled hypertension, history of hypertensive crisis or hypertensive encephalopathy;
10. Severe pulmonary hypertension that cannot be controlled by medication;
11. Severe coagulopathy, or those receiving thrombolytic treatment or requiring continuous anticoagulant or antiplatelet therapy for any reason;
12. History of autoimmune diseases such as rheumatoid arthritis, lupus, psoriasis, Crohn's disease, ulcerative colitis, etc.;
13. Major surgical procedure within 4 weeks before the first dose; History of severe allergy to any of the study drugs;
14. Female patients who are pregnant or breastfeeding;
15. Presence of severe psychiatric or psychological disorders.

Where this trial is running

Guangzhou, Guangdong

• Sun Yat-sen Memorial Hospital, Sun Yat-sen University — Guangzhou, Guangdong, China (RECRUITING)

Study contacts

• Principal investigator: Chao LIU, PhD — Department of Biliary and Pancreatic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University
• Study coordinator: Li PANG, PhD

Conditions: Liver Transplantation, Hepatocellular Carcinoma, Liver transplantation, Milan Criteria, Downstaging therapy, Locoregional therapies, Targeted therapy, PD1 inhibitor