CXD101 in Immunotherapy-related Liver Cancer (NCT05873244) | Clinical Trial Compass
Active — Not RecruitingPhase 2
CXD101 in Immunotherapy-related Liver Cancer
Hong Kong26 participantsStarted 2023-08-21
Plain-language summary
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.
Who can participate
Age range
18 Years
Sex
ALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion Criteria:
* Diagnosis of HCC according to the AASLD guideline20
* Prior treatment with systemic treatment consisting of immune checkpoint inhibitors (anti-PD1, anti-PDL1 or anti-CTLA4)
* The duration of previous ICI must be 6 weeks or longer to avoid chance of pseudo-progression
* Eastern Cooperative Oncology Group (ECOG) Performance status of 0-1
* Adequate hematological function:
* Absolute neutrophil count (ANC) ≥ 1.5 x109/L; Platelets ≥ 100 x 109/L and Hemoglobin ≥ 8g/dL
* Adequate renal function:
* Urine protein/creatinine ratio ≤ 1 mg/mg (≤ 113.1 mg/mmol) or 24-hour urine protein \< 1g
* Serum creatinine ≤ 1.5 × upper limit of normal or calculated creatinine clearance ≥ 40 mL/min (according to the Cockcroft-Gault equation)
* Adequate hepatic function parameters:
* Total bilirubin ≤ 2 mg/dL (≤ 34.2 μmol/L)
* Serum albumin ≥ 2.8 g/dL (≥ 28 g/L)
* Alanine aminotransferase (ALT) \< 3.0 upper limit of normal (ULN)
Exclusion Criteria:
* Previous development of severe autoimmune complications from immune checkpoint inhibitors
* History of moderate to sever autoimmune disease requiring steroid use
* History of organ transplant
* Prior use of lenvatinib or sorafenib
* Disease involvement/thrombosis of major vessels (including main trunk of portal vein, inferior vena cava or pulmonary artery)
* More than two lines of systemic therapy (i.e., study treatment must be second-line or third-line treatment)
* Clinically significant bleeding events (eg.. esophageal varices) …
Questions worth asking your doctor
Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.
1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?
Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.
Questions for the trial coordinator
The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.
What they're measuring
1
The progression-free survival in HCC patients treated with CXD101 plus Geptanolimab and control arm