Actively Recruiting
CXD101 in Immunotherapy-related Liver Cancer
Led by Stephen Chan Lam · Updated on 2025-03-21
44
Participants Needed
2
Research Sites
227 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
For hepatocellular carcinoma (HCC), durable responses and improved survivals have been reported in clinical trials on immune checkpoint inhibitor (ICI)-based treatment. However, resistance to ICI is increasingly encountered in clinical practice in HCC patients. Various approaches are currently evaluated in clinical setting to tackle acquired resistance during treatment of ICIs in HCC. Our group has a track record of studying the role of histone deacetylases (HDACs) in mediating resistance to ICI in HCC. First, based on single-cell sequencing data of serial biopsy of tumor in our phase II clinical trial on pembrolizumab in HCC (NCT03419481), the investigators reveal an upregulation of class 1 HDAC in patients with acquired resistance to pembrolizumab, which was associated with reduced lymphoid/myeloid cellular ratio in the tumor. Further, the investigators showed that HDAC8, a class 1 HDAC, could diminish the efficacy of anti-programmed cell death (ligand)-1 (PD\[L\]-1) by the mechanism of T-cell exclusion from the tumor environment (SciTranl Med. 2021;13:online). Finally, the investigators combine CXD101, a potent selective class I HDAC inhibitor, with anti-PD(L)-1 in orthotopic immunocompetent HCC mouse model with resistance to anti-PD(L)-1 treatment and find that the combination regimen could reverse the resistance phenotype and significantly improve survivals of mice than either CXD101 or anti-PD(L)-1 alone.
CONDITIONS
Official Title
CXD101 in Immunotherapy-related Liver Cancer
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Diagnosis of hepatocellular carcinoma (HCC) based on AASLD guidelines
- Prior treatment with immune checkpoint inhibitors (anti-PD1, anti-PDL1, or anti-CTLA4)
- Previous immune checkpoint inhibitor treatment lasted 6 weeks or longer
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Adequate blood function: neutrophil count ≥ 1.5 x10^9/L; platelets ≥ 100 x10^9/L; hemoglobin ≥ 8 g/dL
- Adequate kidney function: urine protein/creatinine ratio ≤ 1 mg/mg or 24-hour urine protein < 1 g; serum creatinine ≤ 1.5 times upper normal limit or creatinine clearance ≥ 40 mL/min
- Adequate liver function: total bilirubin ≤ 2 mg/dL; serum albumin ≥ 2.8 g/dL; alanine aminotransferase (ALT) less than 3 times upper normal limit
You will not qualify if you...
- History of severe autoimmune complications from immune checkpoint inhibitors
- Moderate to severe autoimmune disease requiring steroid treatment
- History of organ transplant
- Previous use of lenvatinib or sorafenib
- Disease involving or thrombosis of major vessels (portal vein, inferior vena cava, pulmonary artery)
- More than two lines of systemic therapy prior to this study
- Clinically significant bleeding events within the last 3 months
- Moderate or severe ascites
- Child-Pugh B or C liver function
- Systolic blood pressure of 200 mmHg or higher
- Pregnant or breastfeeding women
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Trial Site Locations
Total: 2 locations
1
Department of Clinical Oncology, Prince of Wales Hospital
Hong Kong, Hong Kong
Actively Recruiting
2
School of Biomedical Science, The Chinese University of Hong Kong
Hong Kong, Hong Kong
Active, Not Recruiting
Research Team
S
Stephen Chan, MD, FRCP
CONTACT
N
Nicole Yim, RN
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
2
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