Gall Bladder Cancer

Checkpoint inhibitor therapy represents a significant advance in cancer care. The interaction between PD-1 and PD-L1 induces immune tolerance, and the inhibition of this interaction is an effective treatment strategy for numerous malignancies. Despite its demonstrated potential, immunotherapy is not currently thought to be an effective intervention in the treatment of several immunologically "cold" tumors such as prostate cancer, biliary tract cancers, soft tissue sarcomas, well-differentiated neuroendocrine tumors, microsatellite stable colorectal cancer, pancreatic cancer, and non-triple negative breast cancer. Vascular endothelial growth factor (VEGF) is thought to play a key role in modulating the anti-tumor immune response. Vascular endothelial growth factor (VEGF) is secreted by tumors and leads to endothelial cell proliferation, vascular permeability, and vasodilation. This in turn leads to the development of an abnormal vasculature with excessive permeability and poor blood flow, limiting immune surveillance. In addition, VEGF inhibits dendritic cell differentiation, limiting the presentation of tumor antigens to CD4 and CD8 T cells. Vascular endothelial growth factor (VEGF). VEGF tyrosine kinase inhibitors (TKIs) VEGF-TKIs are currently utilized in the treatment of a variety of malignancies and are widely utilized in combination with checkpoint blockade in the treatment of clear cell kidney cancer. Through the inhibition of VEGF, it may be possible to potentiate the effect of immune checkpoint blockade even in tumors which have traditionally been thought to be unresponsive to immunotherapy. This study aims to evaluate the combination of the immune checkpoint inhibitor atezolizumab and the VEGF-TKI tivozanib in a variety of tumors which have a low response rate to checkpoint inhibitor therapy alone.

This clinical trial studies whether an exercise program can be successfully delivered to patients receiving treatment for cancer through virtual sessions and allow patients to exercise in their own home. Treatments for cancer can cause side effects such as fatigue and loss of strength. These side effects can make it difficult to work, take care of family, and do other things the patient wants to do. Preliminary research shows that exercise can help prevent some of these side effects, but it can be more difficult to start an exercise program when a patient is receiving cancer treatment. The exercise program in this study is delivered through telehealth (TH) video calls. The TH sessions are delivered by trained staff that supervise resistance exercises. The trained staff also provide guidance to the patient on completing unsupervised aerobic sessions on their own. This may be a successful way to deliver an exercise program and make it easier for cancer patients to exercise in their own home during treatment.

This is a phase 2 pragmatic study that evaluates the clinical benefit of continuing systemic therapy with the addition of locally ablative therapies for oligo-progressive solid tumors as the primary objective. The primary outcome measure is the time to treatment failure (defined as time to change in systemic failure or permanent discontinuation of therapy) following locally ablative therapy.

This study will evaluate the effectiveness of T-DXd in patients with HER2-positive (IHC 3+) locally advanced, unresectable, or metastatic solid tumors who have received prior systemic treatment for metastatic or advanced disease and have no satisfactory alternative treatment options in a real-world setting in the US

The Phase 2 monotherapy portion of this study is currently enrolling and will evaluate the efficacy and safety of PC14586 (INN rezatapopt) in participants with locally advanced or metastatic solid tumors harboring a TP53 Y220C mutation. The Phase 1 portion of the study will assess the safety, tolerability and preliminary efficacy of multiple dose levels of rezatapopt as monotherapy and in Phase 1b in combination with pembrolizumab.

Checkpoint inhibitor therapy represents a significant advance in cancer care. The interaction between PD-1 and PD-L1 induces immune tolerance, and the inhibition of this interaction is an effective treatment strategy for numerous malignancies. Despite its demonstrated potential, immunotherapy is not currently thought to be an effective intervention in the treatment of several immunologically "cold" tumors such as prostate cancer, biliary tract cancers, soft tissue sarcomas, well-differentiated neuroendocrine tumors, microsatellite stable colorectal cancer, pancreatic cancer, and non-triple negative breast cancer. Vascular endothelial growth factor (VEGF) is thought to play a key role in modulating the anti-tumor immune response. Vascular endothelial growth factor (VEGF) is secreted by tumors and leads to endothelial cell proliferation, vascular permeability, and vasodilation. This in turn leads to the development of an abnormal vasculature with excessive permeability and poor blood flow, limiting immune surveillance. In addition, VEGF inhibits dendritic cell differentiation, limiting the presentation of tumor antigens to CD4 and CD8 T cells. Vascular endothelial growth factor (VEGF). VEGF tyrosine kinase inhibitors (TKIs) VEGF-TKIs are currently utilized in the treatment of a variety of malignancies and are widely utilized in combination with checkpoint blockade in the treatment of clear cell kidney cancer. Through the inhibition of VEGF, it may be possible to potentiate the effect of immune checkpoint blockade even in tumors which have traditionally been thought to be unresponsive to immunotherapy. This study aims to evaluate the combination of the immune checkpoint inhibitor atezolizumab and the VEGF-TKI tivozanib in a variety of tumors which have a low response rate to checkpoint inhibitor therapy alone.

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.

The goal of this prospective observational study is to evaluate whether Gallium-68 Fibroblast Activation Protein Inhibitor (FAPI) PET/CT can improve detection, staging, and recurrence assessment in adult patients (≥18 years) with suspected or confirmed biliary tract cancers, including gallbladder cancer, cholangiocarcinoma, and post-treatment suspected recurrence. The main question(s) this study aims to answer are: Can FAPI PET/CT provide greater sensitivity, specificity and diagnostic accuracy for primary tumors, nodal disease, and metastatic lesions compared to standard FDG PET/CT? Does FAPI PET/CT offer additional diagnostic yield that may affect clinical decision-making and staging, potentially reducing need for invasive staging procedures? Researchers will compare FAPI PET/CT with FDG PET/CT to see if FAPI improves detection of metastatic or recurrent disease, especially peritoneal or liver metastasis and lymph node involvement. Participants will: Provide written informed consent. Undergo FAPI PET/CT imaging (baseline and/or at suspected biochemical or radiologic recurrence). Have quantitative imaging parameters evaluated (SUVmax, tumor-to-liver ratios, metabolic volume). May undergo comparison with FDG PET/CT and/or follow-up imaging or histopathology as gold standard.

This is a research study of an experimental drug called ACC-1898. ACC-1898 is an oral tyrosine kinase inhibitor (TKI) that blocks several proteins kinases which may help cancer cells grow and spread. The purpose of this Phase 1 clinical trial is to find a safe dose of ACC-1898 and to understand how the body absorbs, distributes, and eliminates the drug (pharmacokinetics / PK). The study will also look for early signs that ACC-1898 may slow or shrink tumors and explore possible biological markers related to drug activity. Adults with advanced or metastatic solid tumors who have no remaining standard treatment options may take part. All participants will receive ACC-1898 tablets by mouth once daily in repeating 21-day cycles. Treatment may continue for up to two years if the cancer does not worsen and side effects are manageable. Safety information, laboratory results and imaging scans (CT or MRI) will be collected regularly. The study will first test different dose levels (dose-escalation phase) and may later expand enrollment in selected tumor types once a recommended dose is found.

Biliary tract carcinoma (BTC), including gallbladder cancer, intrahepatic cholangiocarcinoma, and extrahepatic cholangiocarcinoma, ranks sixth in incidence among gastrointestinal malignancies and tenth in cancer-related mortality worldwide. Due to the lack of specific early symptoms, high malignancy, and frequent recurrence and metastasis, the rate of curative resection is only about 16.5%, and the overall 5-year survival rate is less than 5%. Early and accurate detection is therefore critical for improving patient outcomes. Circulating tumor DNA (ctDNA), a fraction of circulating free DNA (cfDNA), carries genetic and epigenetic information from tumor cells and can be detected even at the early stages of cancer development. Among various liquid biopsy biomarkers, ctDNA methylation shows particular advantages in sensitivity and specificity for early cancer detection and monitoring. This study aims to evaluate the application of cfDNA methylation liquid biopsy in the diagnosis and management of BTC.

The Robocop trial is an international multi-centre, single blinded, randomized controlled superiority trial conducted in centres experienced in robotic-assisted liver surgery. Eligible patients for radical cholecystectomy will be randomized in a 1:1 ratio to undergo robotic-assisted or open resection within an enhanced recovery setting. The primary endpoint is time to functional recovery. Secondary endpoints include length of hospital stay, resection margin, number of retrieved lymph nodes, postoperative complications, quality of life, abdominal wall complaints and direct and indirect costs.

Brief Summary: This study is for patients with advanced biliary tract cancer (cancer of the bile ducts or gallbladder). The purpose is to find out if using anti-blood vessel formation drugs after immunotherapy treatment can help patients live longer without their cancer getting worse. What the study compares: Control group: Patients receive standard chemotherapy as first-line treatment, then chemotherapy plus anlotinib (an anti-blood vessel drug) if their cancer progresses Treatment group: Patients receive chemotherapy plus immunotherapy as first-line treatment, then the same second-line treatment as the control group if their cancer progresses Who can join: Patients aged 18-75 with advanced biliary tract cancer that has been confirmed by tissue testing, who have not received immunotherapy or anti-blood vessel drugs before, and who are in good enough health for treatment. What we want to learn: The main goal is to see if patients who received immunotherapy first have better outcomes when they later receive anti-blood vessel treatment. We will measure how long patients live without their cancer getting worse during second-line treatment. Study design: This is a randomized study, meaning patients are assigned by chance to one of the two treatment groups. About 60 patients will participate across multiple hospitals in China. We will also collect blood and tissue samples to better understand how these treatments work. The study will help doctors determine if this treatment sequence could become a new standard approach for patients with advanced biliary tract cancer.

The goal of this clinical trial is to compare two treatment regimes, namely, systemic therapy (chemotherapy and/or immunotherapy) alone vs. systemic therapy and radiation therapy in patients with inoperable but localized gallbladder cancer. The main questions it aims to answer are: * Whether adding radiation therapy to systemic therapy improves overall survival? * What are the effects on other endpoints like cancer-free intervals, side effects, and quality of life? Participants will be randomly assigned to one of the two treatment regimes mentioned earlier by a computer-based program. Researchers will compare survival and quality of life outcomes between the two groups.

For advanced unresectable intrahepatic cholangiocarcinoma and gallbladder cancer, the current standard first-line treatment is a combination of chemotherapy and immunotherapy. However, the efficacy rates remain low. Hepatic artery infusion chemotherapy can reduce systemic drug dosages while increasing local drug concentrations, which is expected to enhance overall efficacy and minimize drug toxicity and side effects. This study utilized a hepatic artery infusion chemotherapy regimen that combines gemcitabine with oxaliplatin, along with the small molecule tyrosine kinase inhibitor lenvatinib and the immune checkpoint inhibitor toripalimab. The aim was to improve treatment efficacy and create opportunities for conversion surgery. The primary endpoint was the objective response rate, while the secondary endpoints included the surgical resection rate, complete pathological response rate (pCR), overall survival (OS), and the incidence of adverse reactions.