Tislelizumab Combined With Huaier Granule as First-line Treatment for Unresectable Hepatocellular Carcinoma

Official title

Tislelizumab Combined With Huaier Granule as First-line Treatment for Unresectable Hepatocellular Carcinoma: A Single-arm Prospective Clinical Trial

Overview

This study is a single-arm prospective clinical trial that enrolled 94 patients with unresectable hepatocellular carcinoma(HCC) who received first-line treatment with tislelizumab combined with Huaier granule. By comparing the objective response rate (ORR) and other data with those from the historical Rational 301 study, the study aims to explore the efficacy and safety of tislelizumab combined with Huaier granule as a first-line treatment for unresectable HCC, as well as its potential to improve patients' quality of life and alleviate HCC-related symptoms.

Interventions

• Drug Tislelizumab plus Huaier granule
  Tislelizumab Combined with Huaier Granule as First-Line Therapy for Unresectable Hepatocellular Carcinoma

Primary outcome measures

• Objective Response Rate [Time frame: through study completion, an average of 1 year]

Secondary outcome measures (5)

• Disease Control Rate [Time frame: through study completion, an average of 1 year]
• Progression-Free Survival [Time frame: From date of treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months]
• Overall Survival [Time frame: From date of treatment until the date of death from any cause, assessed up to 100 months]
• Duration of Response [Time frame: From date of documented objective tumor response until the date of the first recorded disease progression or death from any cause, whichever occurs first, assessed up to 100 months.]
• Incidence of Adverse Events [Time frame: Within 30 days following the final administration.]

Eligibility criteria

Inclusion criteria

• Male or female aged ≥18 years at the time of signing the informed consent form;
• Histologically confirmed diagnosis of HCC;
• BCLC stage C, or BCLC stage B disease that is unsuitable for locoregional therapy or has progressed after locoregional therapy, and is not eligible for curative treatment;
• No prior systemic therapy for HCC. Note: Patients who have previously received local therapy (e.g., TACE) are not excluded;
• Presence of ≥1 measurable lesion according to RECIST v1.1, provided that: the selected target lesion(s) have not been previously treated with local therapy, or the selected target lesion(s) are located within an area of prior local treatment and have subsequently been assessed as progressive disease according to RECIST v1.1;
• Child-Pugh class A liver function within 7 days prior to randomization;
• ECOG performance status ≤1.

Exclusion criteria

• Fibrolamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, or mixed hepatocellular-cholangiocarcinoma;
• Tumor thrombus involving the main portal vein or inferior vena cava;
• Prior local liver therapy (e.g., transarterial chemoembolization, transarterial embolization, hepatic arterial infusion, radiotherapy, radioembolization, or ablation) or any immunotherapy (e.g., interleukin, interferon, thymosin, etc.) within 28 days before enrollment;
• Use of traditional Chinese medicine or patent drugs for cancer control within 14 days before enrollment;
• Grade 2 or higher hepatic encephalopathy at screening or in medical history;
• Presence of pericardial effusion, uncontrolled pleural effusion, or clinically significant ascites at screening, defined as meeting either of the following criteria: (a) ascites detectable by physical examination at screening, or (b) ascites requiring paracentesis during screening;
• History of severe hypersensitivity to other monoclonal antibodies;
• Any clinical evidence of portal hypertension with bleeding esophageal or gastric varices during screening or within 6 months before randomization;
• Toxicities from prior anticancer therapy have not resolved to baseline or stabilized, except for alopecia;
• Any hemorrhagic or thrombotic disease within 6 months before screening, or any anticoagulant therapy requiring monitoring of the international normalized ratio (e.g., warfarin or similar agents);
• History of any active malignancy within 2 years before screening, except for HCC under study in this trial and locally recurrent cancers that have been curatively treated (e.g., resected basal cell or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast);
• Known central nervous system metastases and/or leptomeningeal disease at screening;
• Any active immunodeficiency or autoimmune disease at screening, and/or history of any immunodeficiency or autoimmune disease with potential for recurrence;
• Any condition requiring systemic corticosteroid therapy (at doses >10 mg/day prednisone or equivalent of similar drugs) or other immunosuppressive treatment within 14 days before screening;
• History of interstitial lung disease or non-infectious pneumonia, unless radiation-induced;
• Any severe chronic or active infection requiring systemic antibacterial, antifungal, or antiviral therapy at screening (e.g., tuberculosis), excluding viral hepatitis; known history of human immunodeficiency virus infection;
• Presence of underlying medical conditions that, in the investigator's judgment, may pose risks for receiving the study treatment or complicate the interpretation of adverse events/toxicity;
• History of allogeneic stem cell transplantation or organ transplantation; receipt of any live vaccine within 4 weeks before randomization (Note: seasonal influenza vaccines are generally inactivated and allowed; intranasal vaccines are live and not allowed);
• Any major surgery within 28 days before randomization;
• Female patients who are lactating.

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

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, — Wuhan

Publications

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• Long H, Wu Z. Immunoregulatory effects of Huaier (Trametes robiniophila Murr) and relevant clinical applications. Front Immunol. 2023 Jun 28;14:1147098. doi: 10.3389/fimmu.2023.1147098. eCollection 2023. PMID 37449208
• Chen Q, Shu C, Laurence AD, Chen Y, Peng BG, Zhen ZJ, Cai JQ, Ding YT, Li LQ, Zhang YB, Zheng QC, Xu GL, Li B, Zhou WP, Cai SW, Wang XY, Wen H, Peng XY, Zhang XW, Dai CL, Bie P, Xing BC, Fu ZR, Liu LX, Mu Y, Zhang L, Zhang QS, Jiang B, Qian HX, Wang YJ, Liu JF, Qin XH, Li Q, Yin P, Zhang ZW, Chen XP. Effect of Huaier granule on recurrence after curative resection of HCC: a multicentre, randomised PMID 29802174
• Ren Z, Xu J, Bai Y, Xu A, Cang S, Du C, Li Q, Lu Y, Chen Y, Guo Y, Chen Z, Liu B, Jia W, Wu J, Wang J, Shao G, Zhang B, Shan Y, Meng Z, Wu J, Gu S, Yang W, Liu C, Shi X, Gao Z, Yin T, Cui J, Huang M, Xing B, Mao Y, Teng G, Qin Y, Wang J, Xia F, Yin G, Yang Y, Chen M, Wang Y, Zhou H, Fan J; ORIENT-32 study group. Sintilimab plus a bevacizumab biosimilar (IBI305) versus sorafenib in unresectable hep PMID 34143971
• Hashimoto K, Kawaoka T, Emori T, Tanaka A, Shirane Y, Miura R, Fujii Y, Nakahara H, Yamaoka K, Uchikawa S, Fujino H, Ono A, Murakami E, Miki D, Hayes CN, Hiramatsu A, Amioka K, Nonaka M, Aisaka Y, Morio K, Moriya T, Teraoka Y, Kono H, Suehiro Y, Masaki K, Ohya K, Takaki S, Mori N, Tsuji K, Kosaka Y, Nakahara T, Aikata H, Tsuge M, Oka S. Atezolizumab plus Bevacizumab with Transcatheter Arterial Che PMID 41607859
• Qin S, Kudo M, Meyer T, Bai Y, Guo Y, Meng Z, Satoh T, Marino D, Assenat E, Li S, Chen Y, Boisserie F, Abdrashitov R, Finn RS, Vogel A, Zhu AX. Tislelizumab vs Sorafenib as First-Line Treatment for Unresectable Hepatocellular Carcinoma: A Phase 3 Randomized Clinical Trial. JAMA Oncol. 2023 Dec 1;9(12):1651-1659. doi: 10.1001/jamaoncol.2023.4003. PMID 37796513
• Xia C, Dong X, Li H, Cao M, Sun D, He S, Yang F, Yan X, Zhang S, Li N, Chen W. Cancer statistics in China and United States, 2022: profiles, trends, and determinants. Chin Med J (Engl). 2022 Feb 9;135(5):584-590. doi: 10.1097/CM9.0000000000002108. PMID 35143424
• Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4. PMID 33538338

Identifiers

NCT: NCT07413354 · TCH-HCC

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗