AHCC® as Immune Modulator in Cancer Patients Treated With Immunotherapy

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

Overview

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.

Interventions

• Dietary supplement 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 Placebo
  3 grams of dextrin (placebo) taken orally once daily for 6 months or until disease progression or intolerance

Primary outcome measures

• Objective Response Rate (ORR) as assessed by RECIST v1.1 [Time frame: Every 12 weeks up to 24 months]

Secondary outcome measures (6)

• 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]

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Taiwan · 1 center

• No. 138, Shengli Rd., North Dist — Tainan

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. PMID 12076865
• Spierings 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. PMID 18202543
• Daddaoua 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. PMID 17449585
• Park 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. PMID 35514996

Identifiers

NCT: NCT07118735 · B-BR-114-016 · NationalCheng-KungU

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗