ClinicalTrials.gg
RecruitingNCT07793695ZINC-1LT/IOHCCUpdated Sep 21, 2026

Oral Zinc Supplementation Combined With Targeted Immunotherapy for Unresectable or Advanced Hepatocellular Carcinoma

A Phase 2 interventional study of Oral elemental zinc supplementation, 20 mg/day and Oral elemental zinc supplementation, 30 mg/day in Hepatocellular Carcinoma, sponsored by Anhui Provincial Hospital. Recruiting at 1 site in China. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2026-09-21.

Sponsored by Anhui Provincial Hospital · Phase 2, Interventional, and Treatment

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Phase
Phase 2
Study type
Interventional
Enrollment
60
Allocation
Randomized
Ages
18 Years to 75 Years
Sex
All
01

Where this study stands

Counted across the records on this site · 2026-11-13

Among 10 studies in Carcinoma, Hepatocellular by Anhui Provincial Hospital — 6 open to participants now, 7 under way, none of them phase 3. Carcinoma, Hepatocellular · Anhui Provincial Hospital.

Started
2026
the only one that year
Phase 2
4 of 10
4 open now
Registered
10th of 10
by date

Among the 10 studies in Carcinoma, Hepatocellular by Anhui Provincial Hospital, this one is the only one that started in 2026, is one of 4 in phase 2, and was the 10th registered.

Carcinoma, Hepatocellular

3,650 studies on the registry are indexed under Carcinoma, Hepatocellular; 1,062 are open to participants now.

Browse Carcinoma, Hepatocellular studies →

Open to participants now

6 of the 10 studies in Carcinoma, Hepatocellular by Anhui Provincial Hospital are open now, in 1 country. Recruiting first, the newest first:

By country, each count listing its studies:

All 6 open studies →

Where they have run

Who these studies take

Of the 737 Carcinoma, Hepatocellular studies recruiting now, 382 (52%) set no upper age limit and 249 (34%) stop at 75 or younger; 31 take children under 18; 31 take healthy volunteers.

This study: 18 Years to 75 Years · all sexes · no healthy volunteers.

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02

Study summary

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.

03

Conditions studied

  • Hepatocellular Carcinoma

Keywords

  • Hepatocellular carcinoma
  • Targeted therapy plus immunotherapy
  • Zinc supplementation
  • Objective response rate
04

Who can participate

Ages eligible
18 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  1. Male or female participants aged 18-75 years who are able to understand the study and voluntarily provide written .
  2. or cytologically confirmed hepatocellular carcinoma (HCC) that is unresectable, recurrent, or .
  3. Estimated of more than 3 months.
  4. (ECOG) performance status of 0-1.
  5. At least one as defined by v1.1, with no prior local treatment to the measurable lesion.
  6. class A, score 5-6, with no ascites, hepatic encephalopathy, or recent hepatic decompensation.
  7. Barcelona Clinic Liver Cancer (BCLC) stage B that is unsuitable for or no longer suitable for local treatment, or BCLC stage C.
  8. No prior systemic antitumor therapy for unresectable, recurrent, or metastatic HCC, including , anti-VEGF/VEGFR-targeted therapy, tyrosine kinase inhibitors (TKIs), systemic chemotherapy, or other systemic anticancer agents.
  9. Participants must not have received any prior local antitumor treatment, including surgery, ablation, transarterial chemoembolization (TACE), hepatic arterial infusion chemotherapy (HAIC), or radiotherapy.
  10. Planned treatment with targeted therapy plus immunotherapy in accordance with applicable treatment guidelines and clinical practice, with the specific background antitumor regimen determined by the investigator before enrollment. The background regimen should not be changed arbitrarily during the study.
  11. If the background treatment regimen includes bevacizumab or another anti-VEGF monoclonal antibody, the participant must undergo upper gastrointestinal endoscopy during screening or have an evaluable endoscopic examination performed within 6 months before screening. Participants with esophagogastric varices requiring treatment may be enrolled only after appropriate management and when the investigator considers the bleeding risk to be adequately controlled.
  12. Baseline testing for serum zinc, serum copper, and ceruloplasmin must be completed.
  13. Adequate major organ function to receive targeted therapy plus immunotherapy, including:

    • (ANC) ≥1.5 × 10⁹/L
    • count ≥75 × 10⁹/L
    • ≥90 g/L
    • and ALT ≤5 × (ULN)
    • Total ≤1.5 × ULN, or considered by the investigator to be consistent with Child-Pugh class A and safe for enrollment
    • Serum creatinine ≤1.5 × ULN, or ≥50 mL/min
    • ≤1.5, unless the participant is receiving stable anticoagulation therapy and the investigator considers the associated risk to be acceptable.
  14. Able to take the study medication orally and willing to comply with study treatment, follow-up visits, imaging assessments, and blood sample collection requirements.
  15. Participants of must agree to use effective during the study and for the protocol-specified period after the last dose of study treatment.

Exclusion criteria

Exclusion Criteria:

  1. Primary liver cancer histology other than predominant HCC, such as intrahepatic cholangiocarcinoma or combined hepatocellular-cholangiocarcinoma, or the presence of another active requiring systemic treatment.
  2. Prior systemic antitumor therapy for unresectable, recurrent, or HCC. Participants who have previously received , PD-L1, or CTLA-4 inhibitors, or systemic anti-VEGF/VEGFR therapy, will be excluded.
  3. Active disease, a history of severe immune-related adverse events, or requirement for systemic therapy within 14 days before screening.
  4. 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.
  5. Confirmed copper deficiency, Wilson disease, Menkes disease, or other clinically significant disorders of copper metabolism; participants currently receiving zinc salts for the treatment of Wilson disease will be excluded.
  6. Use of zinc-containing supplements, multivitamin/mineral preparations, zinc-containing denture adhesives, or other supplements that may significantly affect zinc or copper levels within 14-28 days before screening, if such products cannot be discontinued.
  7. Conditions that may significantly affect oral drug absorption or adherence, including persistent vomiting, severe diarrhea, short bowel syndrome, active inflammatory bowel disease, gastrointestinal obstruction, severe dysphagia, or any condition that, in the investigator's judgment, would prevent regular oral administration of the study medication.
  8. Known severe to zinc preparations or any drug used in the background targeted therapy plus immunotherapy regimen.
  9. Active severe infection. Participants with positivity accompanied by elevated viral load and and/or AST above the , with evidence of active hepatic inflammation, will be excluded. Participants who are HBsAg-positive but HBV DNA-negative with normal liver biochemistry will not be excluded solely on the basis of HBV carrier status.
  10. Untreated or inadequately treated esophagogastric varices, or other portal hypertension-related lesions considered by the investigator to confer a high bleeding risk; gastrointestinal bleeding, hemoptysis, intracranial hemorrhage, or any other Grade ≥3 bleeding event within 6 months before screening.
  11. Uncontrolled hypertension, severe cardiovascular or cerebrovascular disease, recent myocardial infarction, stroke, or pulmonary embolism, severe arrhythmia, class III-IV heart failure, or any condition that, in the investigator's judgment, would preclude safe treatment with anti-VEGF therapy or a TKI.
  12. Major surgery within 28 days before screening, unhealed open wounds, active peptic ulcer disease, high risk of gastrointestinal perforation or fistula, or any condition that may adversely affect the safety of bevacizumab or other anti-VEGF therapy.
  13. Uncontrolled central nervous system metastases or , or symptomatic CNS disease.
  14. Pregnancy, breastfeeding, or a positive pregnancy test during screening.
  15. Planned use during the study of any antitumor treatment, drug, or nutritional intervention outside the protocol that could interfere with assessment of antitumor efficacy.
  16. Any other condition that, in the investigator's judgment, makes the participant unsuitable for study enrollment, including severe psychiatric illness, poor adherence, inability to complete follow-up, drug or alcohol abuse, or a clearly increased safety risk.
Terms in these criteria, in plain language(28)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

Histologically or cytologically confirmed

The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).

Your pathology report is the document that shows this.

Metastases

Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.

Life expectancy

The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.

ECOG performance status

A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.

0
Fully active, no restrictions.
1
Limited in strenuous activity, but walking and able to do light work, such as housework or office work.
2
Walking and able to look after yourself, but unable to work; up and about more than half of waking hours.
3
Able to look after yourself only in part; in bed or a chair more than half of waking hours.
4
Unable to look after yourself at all; in bed or a chair all day.

Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.

Measurable disease

The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.

The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.

RECIST

The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.

“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.

Child-Pugh class

A score of how well the liver works in people with liver disease such as cirrhosis: class A is mild, B moderate and C severe.

Clinically significant

Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.

PD-1, PD-L1 and checkpoint inhibitors

PD-1, PD-L1 and CTLA-4 are proteins that act as brakes on the immune system. Checkpoint inhibitors, such as pembrolizumab or nivolumab, block them so the immune system can attack a cancer.

PD-L1 can also be measured in a tumour sample. Some scores count stained tumour cells only (TPS); others also count certain immune cells (CPS). The study names the score and the minimum it uses.

Absolute neutrophil count (ANC)

The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.

It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.

Platelets

Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.

Hemoglobin (Hb)

The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).

ALT and AST (liver enzymes)

Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.

Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.

ULN (upper limit of normal)

The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.

“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.

Bilirubin

A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.

Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.

Creatinine clearance (CrCl)

How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.

INR, PT and aPTT (clotting tests)

Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.

Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.

Childbearing potential

Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).

Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.

Contraception

Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.

Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.

Cancer (malignancy)

Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.

Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.

Autoimmune disease

A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.

Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.

Immunosuppression

A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.

Read whether the line is about a condition or about medicines, and which medicines and doses it means.

Hypersensitivity

An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.

Hepatitis B tests

Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.

Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.

NYHA class (heart failure)

The New York Heart Association’s four classes of how much heart failure limits physical activity.

I
No limits: ordinary activity causes no undue tiredness or breathlessness.
II
Slight limits: comfortable at rest, ordinary activity causes symptoms.
III
Marked limits: comfortable at rest, less than ordinary activity causes symptoms.
IV
Symptoms even at rest; any activity makes them worse.

Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.

Leptomeningeal disease

Cancer that has spread to the leptomeninges, the thin layers covering the brain and spinal cord, and the fluid between them. It is not the same as brain metastases.

Criteria often treat it separately, and many studies leave it out even where treated brain metastases are allowed.

Investigational drug or device

A drug or device being studied in a clinical trial.

It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.

05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Single (Outcomes assessor)
Enrollment
60 participants (estimated)

Study arms

  • Active comparator
    Control Group

    Participants will receive standard-of-care targeted therapy plus immunotherapy without additional zinc supplementation.

    Drug: Standard-of-care targeted therapy plus immunotherapy

  • Experimental
    Zinc 20 mg/day Group

    Participants will receive standard-of-care targeted therapy plus immunotherapy together with oral elemental zinc supplementation at a dose of 20 mg/day.

    Drug: Oral elemental zinc supplementation, 20 mg/day · Drug: Standard-of-care targeted therapy plus immunotherapy

  • Experimental
    Zinc 30 mg/day Group

    Participants will receive standard-of-care targeted therapy plus immunotherapy together with oral elemental zinc supplementation at a dose of 30 mg/day.

    Drug: Oral elemental zinc supplementation, 30 mg/day · Drug: Standard-of-care targeted therapy plus immunotherapy

Interventions

  • DrugOral elemental zinc supplementation, 20 mg/day

    Participants 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.

  • DrugOral elemental zinc supplementation, 30 mg/day

    Participants 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.

  • DrugStandard-of-care targeted therapy plus immunotherapy

    The 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.

This study also gives Atezolizumab. No intervention listed here names it: that was found by reading the record.

06

What researchers measure

Primary outcomes

  1. 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%.

    Time frame: At Week 18 after initiation of study treatment

Secondary outcomes

  1. 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.

    Time frame: At Week 9 after initiation of study treatment.

  2. Objective Response Rate (ORR) by mRECIST

    Proportion of participants achieving complete response (CR) or partial response (PR) according to mRECIST for hepatocellular carcinoma.

    Time frame: At Weeks 9 and 18 after initiation of study treatment.

  3. 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.

    Time frame: At Weeks 9 and 18 after initiation of study treatment.

  4. 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.

    Time frame: From enrollment until disease progression or death, whichever occurs first.

  5. Overall Survival

    Time from enrollment to death from any cause. Participants who are alive will be censored at the date of last known survival.

    Time frame: From enrollment until death from any cause.

  6. Change in Serum Zinc Level

    Absolute and relative changes in serum zinc levels from baseline.

    Time frame: At Weeks 3, 6, 9,12,15 and 18 after initiation of study treatment.

  7. Incidence of Copper Deficiency

    Proportion of participants with serum copper or ceruloplasmin levels below the lower limit of normal during treatment.

    Time frame: At Weeks 3, 6, 9,12,15 and 18 after initiation of study treatment.

  8. Zinc Correction Rate

    Proportion of participants with baseline serum zinc \<80 μg/dL who achieve a serum zinc level ≥80 μg/dL at the specified visit.

    Time frame: At Weeks 3, 6, 9,12,15 and 18 after initiation of study treatment.

  9. Change in Peripheral Blood CD3+, CD4+, and CD8+ T-cell Counts

    Change from baseline in the absolute counts of peripheral blood CD3+, CD4+, and CD8+ T cells, measured by flow cytometry.

    Time frame: At Weeks 3, 6, 9,12,15 and 18 after initiation of study treatment.

  10. Change in Ki-67+ Cells Among Peripheral Blood PD-1+CD8+ T Cells

    Change from baseline in the proportion of Ki-67+ cells among peripheral blood PD-1+CD8+ T cells, measured by flow cytometry.

    Time frame: At Weeks 3, 6, 9,12,15 and 18 after initiation of study treatment.

  11. Fold Change in Ki-67+ Cells Among Peripheral Blood PD-1+CD8+ T Cells

    Fold change from baseline in the proportion of Ki-67+ cells among peripheral blood PD-1+CD8+ T cells at Week 3, measured by flow cytometry. A fold change of 2.8 or greater will be explored as an early immune response threshold.

    Time frame: At Week 3 after initiation of study treatment.

07

Study locations

1 of 1 sites recruiting
08

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

09

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reachedSimilar studies: half by the dot; the band is the middle halfHalf of similar studies reached it by the dot; the band is the middle half, from a quarter to three quarters

Start is estimated for Sep 2026; primary completion for Aug 2027, 10 months later.

Of 348 non-industry phase 2 interventional studies under Carcinoma, Hepatocellular, half reached primary completion within 47 months of starting (the median), counting those still running; a quarter within 33 and three quarters within 78. This study's planned 10 months is below that.

Counting every sponsor, half of 428 studies reached it within 43 months; a quarter within 30 and three quarters within 71.

How these figures are worked out, and which studies are left out of them.

Registered
Aug 26, 2026
First posted
Aug 28, 2026
StartEst.
Sep 16, 2026
Primary completionEst.
Aug 1, 2027
CompletionEst.
Dec 31, 2027
Last update
Sep 21, 2026
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Sep 21, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT07793695
Responsible party
Sponsor
First posted
Aug 28, 2026
Start date
Sep 16, 2026 (estimated)
Primary completion
Aug 1, 2027 (estimated)
Completion
Dec 31, 2027 (estimated)
Last update
Sep 21, 2026

Study contacts

Yao Liu, Dr
Contact
liuyao66@ustc.edu.cn
0551-62284121
Hua Lu, MD
Contact
0551-62283822
Lianxin Liu
principal investigator · The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital)

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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