Intrahepatic Cholangiocarcinoma

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetic, pharmacodynamic, preliminary anti-tumor activity, and to determine the recommended Phase II dose (RP2D) of the ALE.P03 monotherapy in adult patients with selected squamous solid tumors.

Randomized multicentre trial comparing two care organisations (ambulatory vs conventional inpatient) for patients undergoing transarterial chemoembolization (TACE) or radioembolization (TARE) for primary liver cancer (Hepato Cellular Carcinoma (HCC) or intrahepatic cholangiocarcinoma (iCCA)). Patients are followed for 7 months to assess patient satisfaction, safety and clinical outcomes. A qualitative implementation study and a medico-economic evaluation (cost analysis and 5-years budget impact analysis) are embedded to assess acceptability, adoption, feasability, and sustainability and to inform scaling.

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 example phase 1/2, open-label, biomarker-selected study evaluates EB-HC01, an allogeneic dual-target CARNK product composed of a 1:1 mixture of HER2-CAR-NK and CEACAM5-CAR-NK cells, in adults with unresectable or metastatic cholangiocarcinoma or other biliary tract cancers after standard therapy. Part A determines safety, dose-limiting toxicities (DLTs), and the recommended phase 2 dose (RP2D) after reduced-intensity lymphodepletion. Part B evaluates preliminary anti-tumor activity, CAR-NK persistence, and biomarker-response associations.

This is a single arm phase II study of pemigatinib and durvalumab combination in patients with FGFR-2 fusion or rearrangement positive intrahepatic cholangiocarcinoma. Each cycle will be 3 weeks. Pemigatinib is administered at 13.5 mg orally daily 2 weeks on and 1 week off. Durvalumab is administered at 1500 mg intravenously once every 3 weeks. Subjects will require a visit with appropriate laboratory work prior to the start of each cycle. Disease assessment will occur every 9 weeks. Subjects will continue treatment until progression per RECIST 1.1, toxicity or subject/physician decision. A maximum of 24 months (about 35 cycles) of pemigatinib and durvalumab treatment from Cycle 1 Day 1 is allowed.

This is a single-center, open-label, phase II clinical trial designed to evaluate the efficacy and safety of chidamide in combination with chemotherapy and immunotherapy as a first-line treatment for patients with advanced intrahepatic cholangiocarcinoma (ICC), a type of liver cancer. The study will enroll approximately 35 patients with histologically or pathologically confirmed unresectable or metastatic ICC who have not received prior systemic therapy. All participants will receive chidamide, an oral HDAC inhibitor, in combination with gemcitabine, cisplatin, and an immune checkpoint inhibitor. Treatment will be administered in 21-day cycles until disease progression, unacceptable toxicity, or other withdrawal criteria are met. The primary study endpoints are objective response rate (ORR), and safety, evaluated by the frequency and severity of adverse events. Secondary endpoints include progression-free survival (PFS), duration of response (DOR), overall survival (OS), and exploratory biomarker analyses. The study aims to assess whether the addition of chidamide to standard chemotherapy and immunotherapy can improve treatment outcomes in this patient population.

This study will compare the safety and effects of HAI floxuridine and dexamethasone combined with the standard chemotherapy drugs gemcitabine and oxaliplatin (GemOx) with those of GemOx alone in people with untreated cholangiocarcinoma that cannot be removed with surgery. The researchers want to find out whether the study treatment works better than the standard chemotherapy to delay progression of disease. For the study treatment to be considered better than the standard treatment, the study treatment should increase the time until progression of disease by an average of 3 months, compared with the usual approach.

VG2025 is a Recombinant Human IL12/15 Dual-Regulated Oncolytic HSV-1 Injection. Currently, one phase I dose escalation safety study has been completed in China and the United States respectively, both demonstrating excellent safety profiles with no dose-limiting toxicities (DLTs) observed and no maximum tolerated dose (MTD) identified. Moreover, it has shown preliminary efficacy in treating advanced tumors. Considering the actual clinical needs and the volume of intratumoral administration, a more appropriate recommended phase 2 dose (RP2D) level has been selected for the phase II clinical trial.

The study hypothesis is that liver transplantation after selective internal radiation therapy (SIRT) and chemotherapy would improve 3-year overall survival in patients with locally advanced (unresectable but non-metastatic) intrahepatic cholangiocarcinoma. It is planned to include 36 patients with locally advanced intrahepatic cholangiocarcinoma, not eligible for initial surgery and without metastases. Participants will be recruited from care facilities in France.

It is sometimes difficult to precisely understand whether a primary liver cancer is a hepatocellular carcinoma or a cholangiocarcinoma. The researchers will develop and validate a liquid biopsy, based on exosomal content analysis and powered by machine learning, to help clinicians differentiate these two cancers before surgery.

The aim of the current study is to determine the potential efficacy of liver transplantation in the form of patients' overall survival (OS) after neoadjuvant systemic therapy in patients with biologically responsive locally advanced non-metastatic intrahepatic cholangiocarcinoma (iCCA) in comparison to patients historically treated with chemotherapy alone.

This is a prospective, single-center, single-arm clinical study. It aims to evaluate the efficacy and safety of a new combination therapy as a first-line treatment for patients with advanced intrahepatic cholangiocarcinoma (ICC) who cannot be treated with surgery. The combined therapy includes hepatic arterial infusion chemotherapy (HAIC) with Liposomal Irinotecan, 5-Fluorouracil, and Leucovorin, along with the oral targeted drug Lenvatinib and an intravenous PD-1 inhibitor (an immunotherapy). A total of 30 participants will be enrolled. The main goal of the study is to measure the Objective Response Rate (ORR), which is the percentage of patients whose cancer shrinks or disappears after treatment.

Single arm unblinded study of simulation-free MRI-guided SABR with adaptive replanning in one session for treatment of patients with liver cancers

The goal of this clinical trial is to help learn about the safety and feasibility of hepatic artery infusion chemotherapy for those who have colorectal liver metastases, both resectable and unresectable, or unresectable intrahepatic cholangiocarcinoma. The main questions it aims to answer are: * safety and feasibility of installing a pump that deliveries chemotherapy to the hepatic artery (the blood vessel that supplies blood to the liver) * help learn more about the safety of patients having pump refills at home or a local clinic versus having it routinely done at the hospital Participants will have surgery to install a pump which is a standard surgical procedure. After surgery, participants will select to either receive treatment at the hospital facility or with a community oncologist that will provide cancer care to participants close to home, rather than in a large hospital or academic medical center. The main treatment on study will last about 3-4 months.

Patients with intrahepatic cholangiocarcinoma (IHC) have relatively aggressive tumors, and the prognosis for most of these patients is dismal. Surgery is the only option that can offer potential cure, but only an estimated 20-25 % are amenable to resection. Down-staging conventional chemotherapy has a relatively low response rate (\< 50 %). Patients will be included into the respective treatment arms based on their tumour characteristics and disease stage, but also based on their ability/preferences, as HAI-FUDR/DEX requires going to Oslo every fortnight for the duration of the treatment and SIRT has some limitations regarding tumour distribution. Data from the MSKCC has suggested a clinically relevant benefit from adding intrahepatic chemotherapy to systemic therapy. HAI-FUDR/DEX is not approved in Norway and can only be evaluated in a protocolized trial. Given the risk of distant disease progression with IHC, the addition of conventional systemic chemotherapy makes good clinical sense, and data from MSKCC supports this approach. SIRT is another modality also applied trans-arterially and directly into the tumour. This treatment is approved in Norway and available in Bergen and in Oslo. It is far less cumbersome to deliver and maintain than HAI-FUDR/DEX. The efficacy and safety of the two treatment groups, HAI-FUDR/DEX and SIRT, will be compared in a parallel cohort (non-randomized) design

The purpose of this research is to see if combining gemcitabine, cisplatin and Durvalumab chemotherapy treatments with a direct tumor therapy called Yittrium-90, will work better together to shrink the tumor and control cancer.

This is a prospective, single-arm, multicenter, phase II trial to evaluate the efficacy and safety of D-TACE-HAIC (GEMOX protocol) in combination with Envafolimab and Lenvatinib for unresectable intrahepatic cholangiocarcinoma.

This study is a single-arm, open-label, exploratory clinical trial, with the primary objective to evaluate the efficacy and safety of the Neoantigen Vaccine plus capecitabine for the treatment of high-intermediate risk recurrent intrahepatic cholangiocarcinoma

The goal of this investigator-initiated, a single-arm, open-label, pilot study is to investigate the safety, tolerability, and efficacy of intravenous HNF4α srRNA treatment in subjects with advanced Intrahepatic Cholangiocarcinoma (ICC). Condition of disease: advanced intrahepatic cholangiocarcinoma Intervention： HNF4α srRNA will be administered intravenously for the treatment of ICC. The dosing regimen is planned for a second dose 14 ± 3 days post-initial treatment, followed by subsequent treatments every 28 ± 7 days, with adjustments made based on patient tolerance and therapeutic response. This is a dose escalation assay employing a i3+3 design to assess escalating HNF4α srRNA dosages: 25 μg, 50 μg, and 100 μg. Post-initial dose, a 14-day dose-limiting toxicities (DLT) observation will evaluate tolerability and safety, guiding dose adjustments or selection of the Recommended Dose (RD) for the expansion phase. Cohorts may include up to 9 participants, adjusted for safety. Drug: HNF4α srRNA, a drug specifically designed to target liver cancer cells and facilitate the expression of HNF4α. According to Amendment 1, patients who have received at least 4 cycles of HNF4α srRNA therapy and have a tumor assessment of SD (stable disease) or PD (progressive disease) per RECIST v1.1 criteria may, after a comprehensive evaluation by the investigator considering the patient's treatment history and the current safety and efficacy data of HNF4α srRNA, continue HNF4α srRNA at the same dose, or have their dose adjusted, in combination with immunotherapy, targeted therapy, or chemotherapy.

This is a Phase III, prospective, randomized, three-arm, double-blind, placebo-controlled, international multicenter study to evaluate the efficacy and safety of toripalimab in combination with lenvatinib and gemcitabine-based chemotherapy compared with gemcitabine-based chemotherapy as first-line treatment for unresectable advanced ICC. This study will enroll approximately 480 patients with unresectable advanced ICC who have received no prior systemic therapy. Patients who meet the requirements will be randomly assigned to Treatment Arm A: Toripalimab, lenvatinib, and gemcitabine-based chemotherapy or Treatment Arm B: Toripalimab, oral placebo, and gemcitabine-based chemotherapy or Treatment Arm C: Intravenous placebo, oral placebo, and gemcitabine-based chemotherapy. All patients will receive standard chemotherapy (GEMOX or GC per Investigator decision) for a maximum of 8 cycles. After the completion of standard chemotherapy, all patients continue to receive maintenance therapy with toripalimab injection or its placebo in combination with lenvatinib mesylate capsule or its placebo until unacceptable toxicity, confirmed disease progression and loss of clinical benefit as determined by the investigators, start of new anti-cancer therapy, death, other conditions requiring termination of study treatment, or the patient meets the criteria for study withdrawal, whichever occurs first. In the absence of unacceptable toxicity, patients who meet criteria for unconfirmed disease progression per RECIST v1.1 while receiving toripalimab, lenvatinib, or their placebos will be permitted to continue treatment if their clinical status or symptoms are stable or improved (as determined by the investigators) or until loss of clinical benefit. Patients with confirmed disease progression should discontinue toripalimab, lenvatinib, or their placebos. Tumor assessments will be performed at screening and during the study treatment per protocol. In the absence of progression, tumor assessments will continue as scheduled, regardless of whether study treatment ends, until confirmed disease progression or other criteria for study withdrawal are met, whichever occurs first. Patients who meet RECIST v1.1 criteria for progression should undergo tumor assessments as scheduled if clinical benefits of continuing study treatment are determined by investigators until progression is confirmed per iRECIST (iCPD), or the criteria for study withdrawal are met, whichever occurs first. Computerized tomography (CT)/magnetic resonance imaging (MRI) scans for efficacy evaluation will be performed at baseline, every 6 weeks (Q6W) in the first year (52 weeks), and every 9 weeks (Q9W) in the second year (after week 52). All AEs and concomitant medications during the study will be recorded. An end-of-treatment (EOT) visit will be performed within 30 days after the last dose of study treatment or termination of study treatment is confirmed by the investigator. After the EOT visit, follow-up for survival (telephone visit is allowed) will be conducted and AEs and subsequent anti-cancer therapy will be collected.

The goal of this clinical trial is to learn if additional chemotherapy by means of a chemo pump can prevent return of disease in adult patients with bile duct cancer in the liver that can be treated with surgery. The main questions it aims to answer are: * Does addition of chemotherapy by means of a chemo pump lead to less return of disease within the liver two years after surgery? * Does addition of chemotherapy by means of a chemo pump lead to longer survival of patients? * Does addition of chemotherapy by means of a chemo pump lead to an increase in quality of life? Participants will receive an implanted chemo pump, through which additional chemotherapy will be given to the liver in addition to surgery.

Clinical Study on the efficacy and safety of HAIC（GEMOX）and Lenvatinib combined with Adebrelimab neoadjuvant therapy for resectable Intrahepatic Cholangiocarcinoma with high-risk recurrence factors.

The objective of this study is to evaluate the efficacy and safety of Lenvatinib plus Sintilimab in patients with advanced liver cancer progressed after treatment with immune checkpoint inhibitors.

The objective of this study is to evaluate the efficacy and safety of TACE combined with Tislelizumab in patients with advanced intrahepatic cholangiocarcinoma after progression on first-line systemic therapy.

The objective of this study is to evaluate the efficacy and safety of cryoablation combined with anti-pd-1 antibody in patients with advanced hepatocellular carcinoma after progression on first line systemic therapy.