Liver transplantation in hepatocellular carcinoma after tumour downstaging (XXL): a randomised, controlled, phase 2b/3 trial.
Vincenzo Mazzaferro, Davide Citterio, Sherrie Bhoori...
https://pubmed.ncbi.nlm.nih.gov/32615109Actively Recruiting
Phase 2
Age: 18Years - 75Years
All Genders
ID05475613
Downstaging Protocol Containing Immunotherapy for Hepatocellular Carcinoma Beyond Milan Criteria Before Liver Transplantation
Led by Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University · Updated on 2024-11-29
59
Participants Needed
1
Research Sites
52 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are evaluating a new treatment approach for patients with hepatocellular carcinoma (HCC) that extends beyond the standard Milan criteria used for liver transplantation. This phase II study aims to assess the safety and effectiveness of a downstaging protocol that includes immunotherapy, specifically Anti-PD-1 inhibitors, combined with other therapies. This approach is designed to improve outcomes for patients who currently face limited options due to tumor size or spread, particularly considering the shortage of donor organs and risk of tumor recurrence after transplantation. The study involves four phases. First, eligible patients receive downstaging treatment with Anti-PD-1 inhibitors every 3 to 4 weeks intravenously, combined with locoregional or targeted therapies decided by a multidisciplinary team. Patients who meet defined criteria for successful downstaging within 12 treatment cycles move to an observation phase lasting at least 3 months, where additional non-immunotherapy treatments are not allowed. Those maintaining tumor control are then placed on a liver transplant waiting list, followed by a bridging phase where optional non-immunotherapy treatments may be given before undergoing liver transplantation. Post-transplant, patients are monitored unless contraindications arise. Participants will undergo various assessments throughout the study, including tumor response evaluations by imaging criteria, blood tests such as alpha-fetoprotein levels, and survival predictions using established models. Researchers will monitor event-free survival at two years after transplantation as the primary outcome, along with overall survival rates, graft function, and rejection rates. The study also tracks the success of tumor downstaging and safety during all phases, with participants followed up through transplantation and beyond for comprehensive evaluation.
CONDITIONS
Brief Title
Downstaging Protocol Containing Immunotherapy for HCC Beyond the Milan Criteria Before Liver Transplantation
Who Can Participate
Age: 18Years - 75Years
All Genders
Eligibility Criteria
You may qualify if you...
- Provide written informed consent and agree to follow the study schedule and tests
- Diagnosed with hepatocellular carcinoma confirmed by pathology, cytology, or imaging according to guidelines
- Tumor beyond Milan criteria without extrahepatic or lymph node metastases
- Child-Pugh score 7 or less, with controlled ascites and no encephalopathy
- ECOG performance status 0 to 2; KPS score 60 or higher
- No immunotherapy received within 6 months before enrollment
- Adequate bone marrow, liver, and kidney function
- Predicted survival before liver transplant more than 12 weeks
- No other deadly cancers outside the liver in past 5 years
- Well-controlled hypertension if present
- Use barrier contraception during and for 6 months after the trial
- Willing and able to comply with study requirements and follow-up
You will not qualify if you...
- Diagnosed with cholangiocellular carcinoma, mixed liver cancer, or other rare liver cancers
- Recurrent liver cancer without complete remission or R0 resection
- Uncontrolled infections, alcoholism, drug abuse, serious heart, lung, brain diseases, severe psychiatric illnesses, HIV, or active tuberculosis
- Severe portal hypertension with high bleeding risk
- History of bleeding from portal hypertension in past 6 months
- Life-threatening events in past 6 months such as heart attack, stroke, heart failure, or major bleeding
- Severe enlarged spleen causing low white blood cells or platelets
- History of severe hepatic encephalopathy or symptoms needing long-term drainage
- Uncontrolled hypertension or hypertensive crisis history
- Severe pulmonary hypertension not controlled by medication
- Severe blood clotting problems or needing ongoing blood-thinning treatment
- History of autoimmune diseases like rheumatoid arthritis, lupus, psoriasis, Crohn's disease, or ulcerative colitis
- Major surgery within 4 weeks before first treatment or severe allergy to study drugs
- Pregnant or breastfeeding women
- Severe psychiatric or psychological disorders
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
1
2
3
Your Study Journey
Screening
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 screening and enrollment visit
Run-in Period
Duration - Up to 12 cycles of treatment given every 3 to 4 weeks
Participants undergo downstaging treatment containing immunotherapy and other combination regimens decided by the multidisciplinary team to reduce tumor size and meet criteria for successful downstaging.
Up to 12 intravenous treatment visits every 3 to 4 weeks
Observation
Duration - At least 3 months
Participants who reach the successful downstaging criteria enter an observation phase lasting at least 3 months where they may optionally receive tyrosine kinase inhibitors but not other anti-tumor treatments.
Visits as needed during observation
Waiting and Bridging
Duration - Variable duration until liver transplantation
Participants who maintain tumor control enter the waiting period for liver transplantation and may optionally receive non-immunotherapy bridging treatments determined by the medical team.
Visits as needed during waiting period
Liver Transplantation and Post-transplantation
Duration - Duration of transplantation and immediate post-transplant care
Participants undergo liver transplantation unless contraindications arise during the waiting phase, followed by post-transplant care.
1 transplantation procedure visit and subsequent post-transplant follow-up visits
Trial Site Locations
Total: 1 location
1
Sun Yat-sen Memorial Hospital, Sun Yat-sen University
Guangzhou, Guangdong, China, 376032
Actively Recruiting
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Research Team
L
Li PANG, PhD
L
Leibo Xu, PhD
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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Published Research Related To This Trial
Immunotherapy as a Downstaging Therapy for Liver Transplantation.
Birgit Schwacha-Eipper, Iulia Minciuna, Vanessa Banz...
https://pubmed.ncbi.nlm.nih.gov/32171041Advances in immunotherapy for hepatocellular carcinoma.
Bruno Sangro, Pablo Sarobe, Sandra Hervás-Stubbs...
https://pubmed.ncbi.nlm.nih.gov/33850328Hepatocellular carcinoma downstaging for liver transplantation in the era of systemic combined therapy with anti-VEGF/TKI and immunotherapy.
Nguyen H Tran, Sergio Muñoz, Scott Thompson...
https://pubmed.ncbi.nlm.nih.gov/35765265UNOS Down-Staging Criteria for Liver Transplantation of Hepatocellular Carcinoma: Systematic Review and Meta-Analysis of 25 Studies.
Darren Jun Hao Tan, Wen Hui Lim, Jie Ning Yong...
https://pubmed.ncbi.nlm.nih.gov/35181565Ten-Year Outcomes of Liver Transplant and Downstaging for Hepatocellular Carcinoma.
Parissa Tabrizian, Matthew L Holzner, Neil Mehta...
https://pubmed.ncbi.nlm.nih.gov/35857294