Clinical trials

According to current clinical guidelines, first-line treatment for advanced biliary tract cancer (BTC) is the gemcitabine plus cisplatin (GC) regimen combined with immunotherapy, which has been shown to improve patient outcomes. Additionally, the combination of radiotherapy and immunotherapy may synergistically enhance antitumor efficacy. Therefore, this study aims to assess the efficacy and safety of first-line treatment with radiotherapy in combination with sintilimab and gemcitabine/cisplatin versus sintilimab in combination with gemcitabine/cisplatin in patients with previously untreated, unresectable locally advanced or metastatic BTC.

This clinical trial aims to learn whether daidzein can improve liver tissue changes in adults with metabolic dysfunction-associated steatotic liver disease, also called MASLD. MASLD is a liver condition linked to extra fat in the liver and metabolic problems such as obesity, diabetes, abnormal blood lipids, or high blood pressure. Daidzein is a natural compound found in soy. Earlier laboratory studies suggest that daidzein may help protect the liver. This study will test whether taking daidzein for a short time before surgery can improve liver tissue findings in people with MASLD. The main questions this study aims to answer are: Does short-term daidzein treatment improve liver tissue injury in people with MASLD? Is daidzein safe and well tolerated before surgery? Are changes in blood or urine equol levels related to the effects of daidzein? Equol is a substance made by gut bacteria after some people take daidzein. Researchers will compare people who take daidzein before surgery with people who receive standard care without daidzein. Participants will: Be adults with MASLD who are scheduled for elective gallbladder surgery or another benign biliary surgery. Be randomly assigned to take daidzein or to receive standard care without daidzein. Take daidzein by mouth for 28 days before surgery if assigned to the daidzein group. Avoid soy foods during the study period. Provide blood and urine samples. Have a small liver tissue sample collected during surgery. Be followed for safety and recovery after surgery. The liver tissue sample will be used to check liver fat, inflammation, and liver cell injury. Researchers will also study markers related to liver injury, immune activity, and how the body responds to daidzein.

This is a single-center, prospective, non-randomized, open-label, phase II clinical trial aiming to evaluate the efficacy and feasibility of using patient-derived tumor organoid drug sensitivity testing (ODST) to guide personalized adjuvant therapy in patients with primary liver cancer (HCC) following curative liver resection. A total of 56 eligible patients will be enrolled. Tumor tissues obtained during surgery will be used to establish organoid cultures. Drug sensitivity testing will be performed on a panel of approved targeted and immunotherapeutic agents (including Apatinib, Atezolizumab + Bevacizumab, Donafenib + Toripalimab, Sintilimab, and FOLFOX) to identify the most effective treatment for each patient. Patients for whom organoid testing fails or results are unavailable within the specified timeframe will receive standard Lenvatinib treatment. The primary endpoint is Recurrence-Free Survival (RFS). Secondary endpoints include Overall Survival (OS) and safety profiles. The study seeks to provide a novel strategy for personalized adjuvant therapy in HCC to improve patient outcomes.

Intrahepatic cholangiocarcinoma (ICC) has a poor prognosis. The aim of this study is to investigate the efficacy and safety of GP-HAIC combined with immunosuppressants in the treatment of initially unresectable ICC patients, as well as its role in conversion therapy. A prospective study was conducted on the data of locally advanced unresectable ICC patients receiving GC-HAIC combined with immunosuppressive therapy, evaluating the treatment efficacy and safety.

This is a prospective, non-randomized, open-label, single-center phase II clinical trial. It aims to evaluate the efficacy and feasibility of using patient-derived tumor organoid drug sensitivity testing (DST) to guide personalized systemic therapy for patients with unresectable hepatocellular carcinoma (HCC). A total of 94 eligible patients will be enrolled and grouped based on patient preference into either the Organoid-Directed Therapy group or the Control group (standard therapy). Tumor tissues obtained via biopsy will be used to establish organoid cultures. Drug sensitivity testing will be performed on a pre-defined panel of approved regimens (including Atezolizumab + Bevacizumab, Sintilimab + Bevacizumab biosimilar, Apatinib + Camrelizumab, Donafenib, Lenvatinib, Tislelizumab, Sorafenib, and FOLFOX4) to identify the most effective treatment. Patients for whom organoid construction fails or valid DST results are unavailable within one month will cross over to the control group to receive standard therapy. The co-primary endpoints are Objective Response Rate (ORR) and Progression-Free Survival (PFS), both assessed according to RECIST 1.1. Secondary endpoints include Overall Survival (OS) and safety profiles. The study seeks to provide a novel, personalized treatment strategy to improve outcomes for patients with advanced, unresectable HCC.

This is a prospective, non-randomized, open-label, single-center phase II clinical trial. It aims to evaluate the efficacy and feasibility of using patient-derived tumor organoid drug sensitivity testing (ODST) to guide personalized systemic therapy for patients with unresectable biliary tract cancers (BTC). A total of 88 eligible patients will be enrolled and grouped based on patient preference into either the ODST-guided group or the control group (standard therapy). Tumor tissues obtained via biopsy will be used to establish organoid cultures. Drug sensitivity testing will be performed on a panel of approved regimens (including GC, GEMOX, Durvalumab+GC, Pembrolizumab+GC, and Toripalimab+Lenvatinib+GEMOX) to identify the most effective treatment. Patients for whom organoid testing fails or results are unavailable within one month will receive standard therapy. The primary endpoints are Objective Response Rate (ORR) and Progression-Free Survival (PFS). Secondary endpoints include Overall Survival (OS) and safety profiles. The study seeks to provide a novel, personalized treatment strategy to improve outcomes for patients with advanced BTC.

Research purpose 1. To evaluate the impact of complex behavioral intervention on the one-year overall survival rate of patients with unresectable liver cancer after comprehensive treatment, a comparative study was conducted between the complex behavioral intervention group and the standard medical care control group, and the dose-response relationship between the intervention intensity and clinical outcomes was explored. 2. Analyze the impact mechanisms of complex behavioral interventions on patients' quality of life, adverse treatment reactions, and key biological indicators, including evaluating clinical outcomes such as 2-year overall survival rate, progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR), as well as the association between changes in related biomarkers and behavioral compliance. 3. Evaluate the implementation effect and sustainability of the "in-hospital face-to-face + wechat platform" hybrid intervention model, including intervention acceptance, long-term behavior maintenance, health economic benefits, and perioperative recovery of patients undergoing down-conversion surgery.

This research plan involves a treatment approach for advanced hepatocellular carcinoma (HCC) in the context of metabolic-associated steatotic liver disease (MASLD). The study aims to compare the efficacy differences between sequential therapy and concurrent therapy using bevacizumab and atezolizumab for advanced HCC in MASLD. The research will focus on evaluating objective response rates, progression-free survival, disease control rates, and overall survival, while utilizing biomarker analysis to elucidate treatment mechanisms. Additionally, the study will examine treatment safety, including the incidence and severity of adverse events.

This study is a prospective, single-arm, open, single-center clinical trial initiated by the investigator. The principal investigators are professors Shen Feng and Zhang Xiaofeng from The Third Affiliated Hospital of Navy Military Medical University (Shanghai Eastern Hepatobiliary Surgery Hospital). Primary Objectives: 1. To evaluate the safety and tolerability of super Hi-TCR-T cells targeting Nectin4/NKG2DL/TROP2/B7H3/GPC3/FAP in the treatment of refractory/recurrent advanced hepatocellular carcinoma (HCC) and other solid tumors. 2. To assess the efficacy of super Hi-TCR-T cells targeting Nectin4/NKG2DL/TROP2/B7H3/GPC3/FAP in the treatment of refractory/recurrent advanced HCC and other solid tumors, focusing on progression-free survival (PFS). Secondary Objectives: 1. To evaluate the efficacy of super Hi-TCR-T cells targeting Nectin4/NKG2DL/TROP2/B7H3/GPC3/FAP in the treatment of refractory/recurrent advanced HCC and other solid tumors at 1, 3, 6, and 12 months, assessing disease control rate (DCR: CR+PR+SD), time to progression (TTP), and overall survival (OS). 2. To observe and assess the quality of life (QOL score) of patients receiving super Hi-TCR-T cell therapy targeting Nectin4/NKG2DL/TROP2/B7H3/GPC3/FAP for refractory/recurrent advanced HCC and other solid tumors. Exploratory Objectives: 1. To evaluate the relationship between the in vivo expansion and persistence of super Hi-TCR-T cells targeting Nectin4/NKG2DL/TROP2/B7H3/GPC3/FAP and disease progression. 2. To explore potential predictive biomarkers. Thirty patients are planned to be recruited for this study. The subjects were advanced HCC patients who had failed second-line therapy or could not tolerate therapy. The expression levels of Nectin4, NKG2DL, TROP2, B7H3, GPC3 and FAP were detected by immunohistochemistry in the pathologic tissues of the primary and metastatic sites. Meanwhile, 20ml peripheral blood was extracted to evaluate the quality of T cells (in vitro proliferation activity and lentiviral transduction efficiency). Patients with positive expression rates of at least 2 targets (excluding FAP) \>10% and qualified T cell quality could be considered for inclusion. Peripheral blood lymphocytes were collected and Hi-TCR-T cells targeting three targets (including FAP) were prepared. After pretreatment with fludarabine + cyclophosphamide chemotherapy (FC regimen), the prepared Hi-TCR-T cells were transfused back, in which the dose of Hi-TCR-T cells at each target was 3.0x106 cells/kg body weight (the dose was the extended therapeutic dose obtained in the previous clinical trial), and the drug was administered by peripheral intravenous infusion. To improve efficacy, Hi-TCR-T cell retransfusion can be prepared by increasing the cell dose of the target or changing the combination of the target as the disease progresses and evaluated by a multidisciplinary team (MDT). Safety and efficacy evaluation and exploratory studies were conducted after reinfusion of Hi-TCR-T cells from screening multiple targets: 1. Safety assessment: at baseline, 4, 7, 10, 2, 3, 4, 8, 12, 16, 20, 6, 9 and 12 months after cell therapy; 2. Effectiveness evaluation: at baseline, 4, 12, 6, 9, 12, 24, and 36 months after cell therapy. Safety assessment: At baseline, 4, 7, 10, 2, 3, 4, 8, 12, 16, 20, 6, 9, and 12 months after cell therapy; 3. Exploratory study: 20ml peripheral blood was collected from patients at baseline, 7 days, 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks, 6 months, 9 months, 12 months after cell therapy, to explore the relationship between the proliferation and survival time of Hi-TCR-T cells in vivo and the changes of disease and peripheral blood cytokines. The start time of the study was defined as the date the first patient was enrolled; The end time of the study was defined as 12 months after the end of medication for the final patient, or all patients died, or all patients had lost follow-up or withdrawn consent (whichever occurred first). The planned recruitment period is 12-18 months.

QL1706 Combined with Lenvatinib and GEMOX as First - Line Treatment for Unresectable Biliary Tract Tumors：A Single - Arm, Open - Label, Multi - Center, Prospective Phase II Clinical Trial (Spring Study)

To evaluate the efficacy and safety of inetetamab in combination with chemotherapy ± immunotherapy as a first-line treatment for HER2-positive advanced biliary tract cancer, providing theoretical evidence and practical guidance for further optimizing treatment regimens and improving therapeutic outcomes.

This study is a single-arm, multicenter Phase II clinical trial designed to preliminarily assess the safety and efficacy of the combination therapy of pemigatinib and durvalumab in the second-line treatment of patients with advanced malignant biliary tract cancer. The study anticipates enrolling 38 participants characterized by the following criteria: 1) A confirmed diagnosis of advanced, metastatic, or unresectable biliary tract cancer by histopathological examination; 2) Presence of FGFR2 fusion or rearrangement confirmed by testing; 3) Prior receipt of first-line treatment for biliary tract cancer. The primary questions the study aims to address are: 1. Can the combination of pemigatinib and durvalumab improve the prognosis of participants with previously treated biliary tract cancer (BTC)? 2. What is the safety profile of the treatment with pemigatinib and durvalumab? Participants will receive: 1. Oral administration of 13.5 mg pemigatinib once daily, in combination with durvalumab 1500 mg via intravenous infusion. 2. Follow-up visits will be scheduled every 6 weeks. Investigators will observe and document the objective tumor response rate of the participants, as well as progression-free survival (PFS), disease control rate (DCR), overall survival (OS), and adverse events.