Liver CancerNCKUHNCT07118735
AHCC® as Immune Modulator in Cancer Patients Treated With Immunotherapy
A study testing A standardized extract of cultured Lentinula edodes mycelia (AHCC®) in people with Liver Cancer and Hepatocellular Carcinoma, run by National Cheng-Kung University Hospital at 1 site in Taiwan.
Trial summary
This is a prospective, double-blind, randomized, placebo-controlled trial to evaluate whether AHCC® (Active Hexose Correlated Compound) can enhance the effect of immunotherapy in liver cancer patients. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Liver Cancer, Hepatocellular Carcinoma
- What is being tested?
- A standardized extract of cultured Lentinula edodes mycelia (AHCC®)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 94 participants
- Where
- 1 siteTaiwan
- Study dates
- 20 Aug 2025to 31 Dec 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1.Liver cancer patient who will receive immunotherapy
- 2.At least one measurable tumor, according to RECIST version 1.1, that has not been treated with any local procedure.
- 3.Age >=20 years old.
- 4.ECOG performance status 0 or 1.
- 5.White blood count >=2,000/microliter ; platelet count >=60,000/microliter.
- 6.Liver transaminases (ALT and AST) <=5 times upper limit of normal values (ULN); total bilirubin <= 2 times ULN; creatinine clearance or eGFR > 50 mL/min (either Cockcroft-Gault or MDRD is acceptable, whichever is higher).
- 7.Subjects with chronic hepatitis B virus infection (HBV surface antigen (HBsAg) positive) must start antiviral therapy with nucleoside analogs (e.g., entecavir or tenofovir, according to current practice guidelines) before start of study drug treatment.
Who cannot join
- 1.Major systemic diseases that the investigator considers inappropriate for participation.
- 2.Any active autoimmune disease or history of known autoimmune disease except for vitiligo, resolved childhood asthma/atopy, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
- 3.Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of this protocol.
- 4.Prior therapy with an anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibody (or any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways).
- 5.Requirement of systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
- 6.Prior organ allograft or allogeneic bone marrow transplantation.
- 7.Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation and in the judgment of the investigator would make the patient inappropriate for entry into this study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
Official title: A Standardized Extract of Cultured Lentinula Edodes Mycelia (AHCC®) as Immune Modulator in Cancer Patients Treated With Immunotherapy: a Phase 2 Double-blind, Randomized, Placebo-controlled Trial
This is a prospective, double-blind, randomized, placebo-controlled trial to evaluate whether AHCC® (Active Hexose Correlated Compound) can enhance the effect of immunotherapy in liver cancer patients.
Read the detailed description
Objectives:
Assess the potential of AHCC® to improve immunotherapy outcomes Evaluate progression-free survival (PFS) Evaluate overall survival (OS) Assess safety and tolerability
Method:
Participants will take 3 grams of AHCC® or placebo orally each day Treatment will continue until disease progression, treatment intolerance or other treatment options become available.
Note:
AHCC® is a novel functional food with immune-modulating potential.
- Conditions
- Liver Cancer, Hepatocellular Carcinoma
- Being tested
- A standardized extract of cultured Lentinula edodes mycelia (AHCC®), Placebo
- Keywords
- AHCC® (Active Hexose Correlated Compound), immunotherapy, liver cancer, functional food
- Medical subject headings
- Liver Neoplasms, Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
A standardized extract of cultured Lentinula edodes mycelia (AHCC®)Dietary supplement
3 grams of AHCC® taken orally once daily for 6 months or until disease progression or intolerance
PlaceboDietary supplement
Also called dextrin
3 grams of dextrin (placebo) taken orally once daily for 6 months or until disease progression or intolerance
| Study group | Role | What they receive |
|---|---|---|
| participants receive oral administration of 3g AHCC® daily | Experimental | 3 grams of AHCC taken orally once daily until disease progression or intolerance Receives: Dietary Supplement: A standardized extract of cultured Lentinula edodes mycelia (AHCC®) |
| Placebo | Placebo comparator | 3 grams of dextrin (placebo) taken orally once daily until disease progression or intolerance Receives: Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR) as assessed by RECIST v1.1
Tumor response will be assessed by imaging (CT scan preferred) every 12 weeks using RECIST version 1.1 criteria. Objective Response Rate (ORR) is defined as the proportion of participants achieving a Complete Response (CR) or Partial Response (PR).
Measured: Every 12 weeks up to 24 months
Secondary outcomes (6)
Progression-Free Survival (PFS) as assessed by RECIST v1.1
PFS is defined as the time from the start of treatment to the first documentation of disease progression or death from any cause, whichever occurs first. Tumor response will be assessed using RECIST version 1.1.
Measured: Up to 24 months
Overall Survival (OS)
OS is defined as the time from initiation of study treatment to death from any cause.
Measured: Up to 36 months
Number of participants experiencing any grade adverse events (AEs) as assessed by CTCAE v4.0
Adverse events will be collected and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Events of any grade will be recorded throughout the study.
Measured: Every 3 weeks during treatment, up to 24 months
Number of participants experiencing serious adverse events (SAEs) as defined by regulatory criteria
SAEs will be recorded and reported according to ICH and local regulatory definitions, including events such as death, life-threatening conditions, hospitalization, disability, or other medically significant events.
Measured: Throughout study participation, up to 24 months
Change in quality of life measured by EORTC QLQ-C30
Quality of life will be assessed using the EORTC QLQ-C30, which evaluates global health status, five functional scales (physical, role, emotional, cognitive, and social), and multiple cancer-related symptoms (e.g., fatigue, pain, nausea).
Scores range from 0 to 100. Higher scores on global health and functional scales indicate better functioning; higher scores on symptom scales indicate worse symptoms.
Measured: Baseline and every 12 weeks, up to 24 months
Change in hepatocellular carcinoma-specific quality of life measured by EORTC QLQ-HCC18
The EORTC QLQ-HCC18 will be used to assess liver cancer-specific symptoms and concerns, including fatigue, body image, nutrition, pain, jaundice, abdominal swelling, and fever.
Each scale/item is scored from 0 to 100. Higher scores indicate worse symptoms or problems.
Measured: Baseline and every 12 weeks, up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Aug 2025
- Study start20 Aug 2025 (estimated)
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Liver CancerStudies of the same condition, open and under way.
- More trials run by National Cheng-Kung University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is a prospective double-blind, randomized, placebo-controlled trial aims to investigate whether add-on of a standardized extract of cultured Lentinula edodes mycelia (AHCC®) can enhance the effect of immunotherapy in cancer patients.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 94 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cheng-Kung University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Yih-Jyh Lin, Principal investigator, National Cheng Kung University Hospital (NCKUH)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07118735
- Sponsor's protocol ID
- B-BR-114-016
- Other IDs
- NationalCheng-KungU
- Acronym
- NCKUH
- Status last verified
- Jul 2025
- First submitted
- 11 Jul 2025
- Last updated
- 12 Aug 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Matsui Y, Uhara J, Satoi S, Kaibori M, Yamada H, Kitade H, Imamura A, Takai S, Kawaguchi Y, Kwon AH, Kamiyama Y. Improved prognosis of postoperative hepatocellular carcinoma patients when treated with functional foods: a prospective cohort study. J Hepatol. 2002 Jul;37(1):78-86. doi: 10.1016/s0168-8278(02)00091-0.
PubMed 12076865Spierings EL, Fujii H, Sun B, Walshe T. A Phase I study of the safety of the nutritional supplement, active hexose correlated compound, AHCC, in healthy volunteers. J Nutr Sci Vitaminol (Tokyo). 2007 Dec;53(6):536-9. doi: 10.3177/jnsv.53.536.
PubMed 18202543Daddaoua A, Martinez-Plata E, Lopez-Posadas R, Vieites JM, Gonzalez M, Requena P, Zarzuelo A, Suarez MD, de Medina FS, Martinez-Augustin O. Active hexose correlated compound acts as a prebiotic and is antiinflammatory in rats with hapten-induced colitis. J Nutr. 2007 May;137(5):1222-8. doi: 10.1093/jn/137.5.1222.
PubMed 17449585Park HJ, Boo S, Park I, Shin MS, Takahashi T, Takanari J, Homma K, Kang I. AHCC(R), a Standardized Extract of Cultured Lentinula Edodes Mycelia, Promotes the Anti-Tumor Effect of Dual Immune Checkpoint Blockade Effect in Murine Colon Cancer. Front Immunol. 2022 Apr 20;13:875872. doi: 10.3389/fimmu.2022.875872. eCollection 2022.
PubMed 35514996
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Standardized Extract of Cultured Lentinula Edodes Mycelia (AHCC®) as Immune Modulator in Cancer Patients Treated With Immunotherapy: a Phase 2 Double-blind, Randomized, Placebo-controlled Trial
- ClinicalTrials.gov ID
- NCT07118735
- Acronym / sponsor ID
- NCKUH / B-BR-114-016
- Conditions
- Liver Cancer, Hepatocellular Carcinoma
- Keywords
- AHCC® (Active Hexose Correlated Compound), immunotherapy, liver cancer, functional food
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 94 participants (estimated)
- Lead sponsor
- National Cheng-Kung University HospitalUniversity, hospital or other
- Study start
- 20 Aug 2025 (estimated)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 31 Dec 2028 (estimated)
- First posted
- 12 Aug 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a prospective, double-blind, randomized, placebo-controlled trial to evaluate whether AHCC® (Active Hexose Correlated Compound) can enhance the effect of immunotherapy in liver cancer patients.
Detailed description
Objectives:
Assess the potential of AHCC® to improve immunotherapy outcomes Evaluate progression-free survival (PFS) Evaluate overall survival (OS) Assess safety and tolerability
Method:
Participants will take 3 grams of AHCC® or placebo orally each day Treatment will continue until disease progression, treatment intolerance or other treatment options become available.
Note:
AHCC® is a novel functional food with immune-modulating potential.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- This is a prospective double-blind, randomized, placebo-controlled trial aims to investigate whether add-on of a standardized extract of cultured Lentinula edodes mycelia (AHCC®) can enhance the effect of immunotherapy in cancer patients.
| Arm | Type | Receives |
|---|---|---|
| participants receive oral administration of 3g AHCC® daily | Experimental | Dietary Supplement: A standardized extract of cultured Lentinula edodes mycelia (AHCC®)3 grams of AHCC taken orally once daily until disease progression or intolerance |
| Placebo | Placebo comparator | Dietary Supplement: Placebo3 grams of dextrin (placebo) taken orally once daily until disease progression or intolerance |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 1.Liver cancer patient who will receive immunotherapy
- 2.At least one measurable tumor, according to RECIST version 1.1, that has not been treated with any local procedure.
- 3.Age >=20 years old.
- 4.ECOG performance status 0 or 1.
- 5.White blood count >=2,000/microliter ; platelet count >=60,000/microliter.
Key exclusion criteria (7 listed)
- 1.Major systemic diseases that the investigator considers inappropriate for participation.
- 2.Any active autoimmune disease or history of known autoimmune disease except for vitiligo, resolved childhood asthma/atopy, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
- 3.Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of this protocol.
- 4.Prior therapy with an anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibody (or any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways).
- 5.Requirement of systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| A standardized extract of cultured Lentinula edodes mycelia (AHCC®)3 grams of AHCC® taken orally once daily for 6 months or until disease progression or intolerance | Dietary supplement | participants receive oral administration of 3g AHCC® daily |
| PlaceboAlso: dextrin3 grams of dextrin (placebo) taken orally once daily for 6 months or until disease progression or intolerance | Dietary supplement | Placebo |
Primary outcome
Objective Response Rate (ORR) as assessed by RECIST v1.1
Time frame: Every 12 weeks up to 24 months
Tumor response will be assessed by imaging (CT scan preferred) every 12 weeks using RECIST version 1.1 criteria. Objective Response Rate (ORR) is defined as the proportion of participants achieving a Complete Response (CR) or Partial Response (PR).
6 secondary outcomes
Progression-Free Survival (PFS) as assessed by RECIST v1.1
Time frame: Up to 24 months
Overall Survival (OS)
Time frame: Up to 36 months
Number of participants experiencing any grade adverse events (AEs) as assessed by CTCAE v4.0
Time frame: Every 3 weeks during treatment, up to 24 months
Number of participants experiencing serious adverse events (SAEs) as defined by regulatory criteria
Time frame: Throughout study participation, up to 24 months
Change in quality of life measured by EORTC QLQ-C30
Time frame: Baseline and every 12 weeks, up to 24 months
Change in hepatocellular carcinoma-specific quality of life measured by EORTC QLQ-HCC18
Time frame: Baseline and every 12 weeks, up to 24 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2025.
- Results publication: PubMed 12076865Matsui Y, Uhara J, Satoi S, Kaibori M, Yamada H, Kitade H, Imamura A, Takai S, Kawaguchi Y, Kwon AH, Kamiyama Y. Improved prognosis of postoperative hepatocellular carcinoma patients when treated with functional foods: a prospective cohort study. J Hepatol. 2002 Jul;37(1):78-86. doi: 10.1016/s0168-8278(02)00091-0.
- Results publication: PubMed 18202543Spierings EL, Fujii H, Sun B, Walshe T. A Phase I study of the safety of the nutritional supplement, active hexose correlated compound, AHCC, in healthy volunteers. J Nutr Sci Vitaminol (Tokyo). 2007 Dec;53(6):536-9. doi: 10.3177/jnsv.53.536.
- Results publication: PubMed 17449585Daddaoua A, Martinez-Plata E, Lopez-Posadas R, Vieites JM, Gonzalez M, Requena P, Zarzuelo A, Suarez MD, de Medina FS, Martinez-Augustin O. Active hexose correlated compound acts as a prebiotic and is antiinflammatory in rats with hapten-induced colitis. J Nutr. 2007 May;137(5):1222-8. doi: 10.1093/jn/137.5.1222.
- Results publication: PubMed 35514996Park HJ, Boo S, Park I, Shin MS, Takahashi T, Takanari J, Homma K, Kang I. AHCC(R), a Standardized Extract of Cultured Lentinula Edodes Mycelia, Promotes the Anti-Tumor Effect of Dual Immune Checkpoint Blockade Effect in Murine Colon Cancer. Front Immunol. 2022 Apr 20;13:875872. doi: 10.3389/fimmu.2022.875872. eCollection 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Yih-Jyh Lin principal investigator
National Cheng Kung University Hospital (NCKUH)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing A standardized extract of cultured Lentinula edodes mycelia (AHCC®) in people with Liver Cancer and Hepatocellular Carcinoma, run by National Cheng-Kung University Hospital at 1 site in Taiwan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 12 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Yung-Yeh Su (+886 67000123 ext. 65181, yysu@nhri.edu.tw), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) as assessed by RECIST v1.1 (time frame: Every 12 weeks up to 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07118735, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Aug 2025.