This study will look at whether adding daily oral zinc supplements to targeted therapy plus immunotherapy may help people with unresectable or advanced hepatocellular carcinoma, a common type of liver cancer.
About 60 participants will take part in this study. Participants will be randomly assigned to one of three groups. One group will receive targeted therapy plus immunotherapy without extra zinc. The other two groups will receive the same type of cancer treatment together with either 20 mg or 30 mg of elemental zinc each day.
The main goal is to compare how many participants have their tumors shrink or disappear by Week 18. Researchers will also look at tumor response at earlier time points, how long the cancer remains under control, overall survival, and treatment safety.
Blood tests will be used to measure zinc and copper levels during the study. Researchers will also study changes in immune cells, including T cells, to better understand whether zinc supplementation may affect the body's immune response to cancer treatment.
This study is designed to explore whether oral zinc supplementation is safe and may improve the effects of targeted therapy plus immunotherapy. The results may help determine which zinc dose should be studied in larger clinical trials.
Male or female participants aged 18-75 years who are able to understand the study and voluntarily provide written informed consent.
Histologically or cytologically confirmed hepatocellular carcinoma (HCC) that is unresectable, recurrent, or metastatic.
Estimated life expectancy of more than 3 months.
Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
Primary liver cancer histology other than predominant HCC, such as intrahepatic cholangiocarcinoma or combined hepatocellular-cholangiocarcinoma, or the presence of another active malignancy requiring systemic treatment.
Prior systemic antitumor therapy for unresectable, recurrent, or metastatic HCC. Participants who have previously received PD-1, PD-L1, or CTLA-4 inhibitors, or systemic anti-VEGF/VEGFR therapy, will be excluded.
Active autoimmune disease, a history of severe immune-related adverse events, or requirement for systemic immunosuppressive therapy within 14 days before screening.
Clinically significant ascites, such as ascites requiring repeated paracentesis, albumin infusion, or showing recent rapid worsening; current or previous hepatic encephalopathy, hepatorenal syndrome, or other clear evidence of hepatic decompensation.
Parallel
Oral elemental zinc supplementation, 20 mg/day
DrugParticipants will receive oral elemental zinc supplementation at a dose of 20 mg/day. Zinc gluconate tablets will be administered orally, 1 tablet twice daily after meals.
Oral elemental zinc supplementation, 30 mg/day
DrugParticipants will receive oral elemental zinc supplementation at a dose of 30 mg/day. Zinc gluconate tablets will be administered orally, 1 tablet three times daily after meals.
Standard-of-care targeted therapy plus immunotherapy
DrugThe background targeted therapy plus immunotherapy regimen will be selected by the investigator based on the participant's clinical condition and standard clinical practice. Permitted regimens include atezolizumab plus bevacizumab and camrelizumab plus apatinib.
Objective Response Rate (ORR) at Week 18
Proportion of participants achieving complete response (CR) or partial response (PR) at Week 18 according to RECIST v1.1. ORR = (CR + PR) / total number of participants in the analysis set × 100%.
Objective Response Rate (ORR) at Week 9
Proportion of participants achieving complete response (CR) or partial response (PR) at Week 9 according to RECIST v1.1.
Objective Response Rate (ORR) by mRECIST
Proportion of participants achieving complete response (CR) or partial response (PR) according to mRECIST for hepatocellular carcinoma.
Disease Control Rate
Proportion of participants achieving complete response (CR), partial response (PR), or stable disease (SD), assessed according to RECIST v1.1 and mRECIST.
Progression-Free Survival
Time from enrollment to the first documented disease progression according to RECIST v1.1 or death from any cause, whichever occurs first.
Click on the lead sponsor to view all of their trials.
