Clinical Research Directory

Sintilimab Combined With Ipilimumab (N01) Plus AG as First-line Therapy for uBTC.

For unresectable and metastatic advanced biliary tract cancers (BTCs), gemcitabine plus cisplatin (GP regimen) has been established as the standard first-line treatment based on the findings of the ABC-02 trial. As the first large-sample phase III randomized clinical trial enrolling patients with locally advanced or metastatic biliary tract cancers, the ABC-02 study demonstrated that the GP regimen improved the efficacy of chemotherapy for biliary tract malignancies and confirmed the synergistic effect between gemcitabine and cisplatin. Phase III trials of immunotherapy combined with chemotherapy have also yielded encouraging outcomes in patients with advanced biliary tract cancers (BTCs). The TOPAZ-1 trial was a global, randomized, double-blind, phase III randomized controlled study evaluating durvalumab or placebo combined with gemcitabine plus cisplatin for advanced biliary tract cancer. A total of 685 patients were randomly assigned to the durvalumab plus GC group (D+GC, n=341) or the placebo plus GC group (PBO+GC, n=344). The median follow-up duration was 23.4 months (20.6-25.2) and 22.4 months (21.4-23.8) for the two groups, respectively. Median overall survival (mOS) was significantly prolonged in the D+GC group compared with the PBO+GC group (12.9 months vs 11.3 months; HR=0.76, 95% CI: 0.64-0.91). OS hazard ratios (HRs) with corresponding 95% CIs indicated consistent clinical benefits of the D+GC regimen across all pre-specified subgroups: initially unresectable disease (HR=0.79, 95% CI: 0.65-0.95), recurrent disease (HR=0.76, 95% CI: 0.49-1.20); and by primary tumor site: intrahepatic cholangiocarcinoma (HR=0.78, 95% CI: 0.62-0.99), extrahepatic cholangiocarcinoma (HR=0.61, 95% CI: 0.41-0.91), and gallbladder cancer (HR=0.90, 95% CI: 0.64-1.25). The 12-month, 18-month and 24-month OS rates were 54.3% vs 47.1%, 34.8% vs 24.1%, and 23.6% vs 11.5% (D+GC vs PBO+GC), respectively. The incidence of grade 3/4 treatment-related adverse events (TRAEs) was 60.9% in the D+GC group versus 63.5% in the PBO+GC group. The rate of treatment discontinuation due to any TRAE was 8.9% and 11.4% in the two groups respectively. KEYNOTE-966 is a randomized, double-blind, placebo-controlled phase III trial conducted across 175 medical centers worldwide. A total of 1069 patients were randomized to receive pembrolizumab plus gemcitabine and cisplatin (pembrolizumab group, n=533) or placebo plus gemcitabine and cisplatin (placebo group, n=536). At the final analysis, the median follow-up time was 25.6 months (IQR: 21.7-30.4). The median OS was 12.7 months (95% CI: 11.5-13.6) in the pembrolizumab group and 10.9 months (95% CI: 9.9-11.6) in the placebo group (HR=0.83, 95% CI: 0.72-0.95; one-sided p=0.034, with a prespecified significance threshold of p=0.0200). Among the treated population, grade 3-4 adverse events were reported in 420 of 529 patients (79%) in the pembrolizumab group and 400 of 534 patients (75%) in the placebo group. Grade 3-4 TRAEs occurred in 369 patients (70%) in the pembrolizumab group and 367 patients (69%) in the placebo group. Deaths attributable to adverse events occurred in 31 patients (6%) in the pembrolizumab group and 49 patients (9%) in the placebo group. Among these, 8 patients (2%) in the pembrolizumab group and 3 patients (1%) in the placebo group died from TRAEs. Although chemoimmunotherapy has become the standard first-line regimen for advanced biliary tract cancers (BTCs), substantial unmet medical needs remain in clinical practice. First, the survival benefit is modest. In the TOPAZ-1 and KEYNOTE-966 trials, the median overall survival (OS) was prolonged by merely 1.3 to 1.8 months with chemoimmunotherapy versus chemotherapy alone. The objective response rate (ORR) remains below 30%, and disease progression eventually occurs in most patients. Second, there is a lack of validated predictive biomarkers. To date, no reliable biomarkers are available to accurately identify patients most likely to benefit from chemoimmunotherapy. Consequently, some patients fail to achieve satisfactory clinical outcomes while suffering from unnecessary treatment-related toxicities. Third, a subset of patients show poor tolerance to current regimens. Cisplatin-induced adverse events such as nephrotoxicity and gastrointestinal reactions may compromise treatment adherence. Therefore, safer chemotherapy combinations and novel combination strategies are urgently required. These limitations indicate that current chemoimmunotherapy regimens require further optimization. Novel and more effective combination treatment strategies need to be explored to maximize clinical benefits and improve patient prognosis.

TRACE-BTC. Relation of Biomarkers and Patients Reported Quality of Life to Outcomes in Patients With Biliary Tract Cancer: a Real- World Cohort

Purpose of the Study: Bile duct cancers are rare and aggressive. About 250 new cases are diagnosed each year in Denmark. These cancers are difficult to detect early, so only about 20% of patients can have surgery when diagnosed. Even after surgery, the cancer often returns, and chemotherapy only slightly reduces the risk of relapse. For patients who cannot have surgery, treatments such as chemotherapy (sometimes combined with immunotherapy) can relieve symptoms and extend life, but their effect is limited. A small number of patients have specific genetic changes in their cancer that can be treated with targeted medicines. Currently, doctors cannot predict which patients will benefit from treatment. Standard monitoring methods like CT scans are expensive, inconvenient, and sometimes unreliable because bile ducts are hard to see clearly on scans. Blood tests that detect cancer DNA in the blood (called circulating tumor DNA or ctDNA) and other biological markers may be a better way to monitor the disease and adjust treatment. These tests could help detect cancer recurrence earlier and determine whether treatment is working. Measuring patients' quality of life and symptoms over time may also help predict treatment benefit and evaluate effectiveness. The goal of this study is to: * Investigate how biomarkers, including ctDNA, can predict disease course, detect relapse, and monitor treatment response. * Identify the best way to measure ctDNA in patients with bile duct cancer. * Examine whether patients' own reports of quality of life and symptoms can help assess treatment effect and prognosis. Study Design and Procedures: This is a prospective cohort study focusing on blood biomarkers and patient-reported symptoms and quality of life. Participants agree to provide blood samples: * Before treatment * During treatment * During follow-up Each sample involves up to 40 ml of blood, with a maximum of 20 samples per patient. The blood will be analyzed for: * ctDNA and genetic changes * Cancer-related markers * Inflammation markers * Immune system markers Tumor tissue samples will also be examined to compare blood and tissue results. Full genome or exome sequencing will not be performed. Samples will be stored in a research biobank. For patients with incurable disease, quality of life and symptom burden will be monitored repeatedly using Danish questionnaires. Participants: The study will include: * Up to 100 patients with potentially curable disease * Up to 200 patients with incurable disease To participate, patients must: * Have confirmed bile duct cancer * Be eligible for curative, additional (adjuvant), or palliative treatment * Be over 18 years old * Provide written and verbal consent Patients cannot participate if they: * Had another cancer within the past 5 years (except early skin cancer or very early cervical cancer) * Cannot safely provide blood samples * Are unable to cooperate with study procedures Risks and Inconveniences: Participants will have extra blood samples taken, usually during regular hospital visits. Possible side effects include mild soreness or small bruises at the needle site. The extra blood amount (40 ml per sample) is considered medically insignificant. Participants will also spend time filling out questionnaires. The number and frequency of questions have been kept as low as possible while still providing meaningful data. Financial Information: Extra costs for blood sampling, laboratory analysis, and data collection will be covered by external research funding managed by Aarhus University Hospital. The researchers have no financial interest in the project. Patients will not receive financial compensation for participating. Recruitment and Consent: Potential participants are identified during routine clinical care. During a planned meeting with a doctor, patients receive written and verbal information about the study, including its purpose, risks, advantages, and disadvantages. The conversation takes place in a calm and private setting. Patients may bring a support person. They have time to ask questions and at least 24 hours to consider participation. Patients can withdraw their consent at any time without affecting their treatment. Consent must be given before any study-related procedures begin. Publication of Results: The results - whether positive or negative - will be presented at national and international conferences and submitted to peer-reviewed scientific journals. Ethical Considerations: All participants receive standard medical treatment. The risks and disadvantages are limited, and participants are unlikely to benefit directly from the study. However, the research may improve how biomarkers and patient-reported outcomes are used to predict prognosis and treatment response, potentially leading to better treatment for future patients with bile duct cancer.

Cosiporfin Sodium for Injection Photodynamic Therapy

Study Design: Multicenter, open-label, Single Group Study Population: Patients with locally advanced or recurrent metastatic extrahepatic cholangiocarcinoma who are inoperable or unwilling to undergo surgery. Primary Research Objective: To preliminarily evaluate the efficacy of photodynamic therapy (PDT) with sodium protoporphyrin combined with gemcitabine and cisplatin (GC regimen) chemotherapy in patients with advanced extrahepatic cholangiocarcinoma complicated by biliary obstruction. Secondary Study Objective: To preliminarily evaluate the safety and tolerability of photodynamic therapy (PDT) with heme porphyrin sodium combined with gemcitabine and cisplatin (GC regimen) chemotherapy in patients with advanced extrahepatic cholangiocarcinoma with biliary obstruction. Primary endpoint: 6-month overall survival rate (6m-OS rate)

Adjuvant Chemotherapy Regimens in Resected Biliary Tract Cancers (TOG/GI-SAFRADJU-2501)

The goal of this observational study is to compare chemotherapy types that are given after surgery for biliary tract cancers. The main question it aims to answer is: Are any of the chemotherapy regimens more effective in preventing recurrence, providing longer survival, or having less toxicity? Nationwide multicenter retrospective data will be collected.

A Study of Tumor-Treating Fields in Combination With Durvalumab and Gemcitabine/Cisplatin in Biliary Tract Cancers

Unresectable BTC represents an area of unmet medical need due to its very aggressive nature, limited treatment options, and poor prognosis. This study is to evaluate the efficacy and safety of adding TTF to the established regimen of durvalumab plus GemCis for the treatment of patients with previously untreated, unresectable BTC.