Clinical Research Directory

A Post Approval Study to Evaluate Safety and Effectiveness of Multicompartmental Dosimetry Planning.

The purpose of this study is to assess the safety and effectiveness of treating a tumor using a different planning method called MCD for the FDA-Approved device, TheraSphere. TheraSphere Microspheres are microscopic radioactive glass spheres that deliver radiation therapy in the liver tissue where they are placed. This study investigates a procedure called multicompartment dosimetry (MCD). When using a multicompartment dosimetry approach, the doctor will look at images of the liver to see where there is tumor to determine where to treat. That area will be divided into "compartments" where the dose to tumor and the healthy liver are calculated separately. The goal of MCD is to give the tumor a higher radiation dose while protecting more of the healthy part of the liver. Traditional planning for the TheraSphere Microspheres procedure uses single compartment dosimetry (SCD) which treats the tumor and the healthy liver as one area so the dose is more evenly distributed and the dose to the tumor may be lower than with the MCD approach. The single compartment approach is standard and is well established however this research study is to see if giving TheraSphere Microspheres with an MCD planning method is safe and effective by evaluating the effect of radiation on the liver as well as how the tumor responds to higher doses

HCC Risk Prediction Model Based on Multimodal Data in Chronic Hepatitis B

The investigators propose to construct and validate an early HCC risk prediction model in a multicenter retrospective cohort of hepatitis B-related fibrosis/cirrhosis patients, using multimodal data encompassing longitudinal clinical data, serum glycomics profiles, and liver biopsy histopathological images.

Liver Cancer Registry Platform

The purpose of the project is to set up a national, prospective, longitudinal, multicenter cohort study with associated satellites, a tumor registry platform, to document uniform data on characteristics, molecular diagnostics, treatment and course of disease, to collect patient-reported outcomes and to establish a decentralized biobank for patients with Hepatocellular Carcinoma (HCC) or Cholangiocarcinoma (CCC) in Germany.

Adaptive Dosing of Immune Checkpoint Inhibitors for Hepatocellular Carcinoma

The goal of this clinical trial is to learn if immunotherapy including nivolumab plus ipilimumab is effective and safe in treating hepatocellular carcinoma.

Hepatic IA Therapy in Stage B or Limited Stage C Hepatoma (HCC)

Intra-arterial (IA) therapy is generally used to treat HCC tumors that are too extensive to excise or treat with potentially curative local therapy. IA therapy takes advantage of the fact that the blood supply of HCC comes predominantly from the hepatic artery compared with the surrounding normal liver which is predominantly supplied by portal venous blood. The intent is to deprive the HCC of its blood supply, leading to the death of the tumor. Traditionally, various methods have been used to block the HCC blood supply, but improvements are needed. This study will investigate a new agent designed in the laboratory to block only tumor blood vessels, not blood vessels in the normal liver.

Building Evidence for Ablative Internal Radiation Therapy in Localized HCC Beyond the Up-To-7 Criteria

At four major centers in Korea, patients with hepatocellular carcinoma (HCC) that exceed the up-to-7 criteria yet remain locally confined will undergo ablative radioembolization using Yttrium-90 glass microspheres, guided by a standardized dosimetry method. Their treatment response, survival outcomes, and adverse events will be monitored for two years following the procedure.

A Phase 1 and 2 Study of VMD-102 in Hepatocellular Carcinoma and Other Solid Tumors

This study is to evaluate the safety and tolerability to determine (i) the recommended Phase 2 dose (RP2D) of VMD-102 (Phase 1), and (ii) preliminary anti-tumor efficacy (Phase 2), in participants with advanced HCC, metastatic uveal melanoma (MUM), renal cell carcinoma (RCC), non-small cell lung cancer (NSCLC), and colorectal cancer (CRC). The pharmacokinetics (PK), preliminary anti-tumor activity, and potential biomarkers of VMD-102 will also be assessed. VMD-102 will be the first selective PKC epsilon (PKCε or PKCe) kinase inhibitor to enter human clinical testing. Preclinical VMD-102 anti-tumor activities in mouse liver/HCC tumor models and preclinical toxicology and pharmacology studies support this study.

A Study to Evaluate the Safety and Tolerability of Pumitamig Alone or In Combination With Ipilimumab in Participants With First-Line Advanced or Unresectable Hepatocellular Carcinoma (HCC) (ROSETTA HCC-206)

The purpose of this study is to evaluate the safety and tolerability of Pumitamig alone or in combination with Ipilimumab in participants with first-line advanced or unresectable Hepatocellular Carcinoma (HCC)

Same-day Radioembolization for Large HCC

In patients who has no sign suggesting high lung shunt fraction (TIPS, hepatic vein invasion, hepatic vein enhancement on arterial phase, dysmorphic intratumoral vessel), planning angiography, MAA scan, and radioembolization are performed in a single day with SIR-Spheres. This prospective registry will prove that the selection criteria is accurate and same-day radioembolization is feasible and safe.

Long-Term Extension Study for Participants Previously Enrolled in an Exelixis-Sponsored Study

The primary objective of this long-term extension study is to allow continued access to study treatment for eligible participants who are deriving clinical benefit in an Exelixis-sponsored study who do not have access to treatment locally.

Streamlining Radioembolization for Small HCC

In patients who has no sign suggesting high lung shunt fraction (TIPS, hepatic vein invasion, hepatic vein enhancement on arterial phase, dysmorphic intratumoral vessel, tumor size \< 5cm), radioembolization is performed without MAA scan with SIR-Spheres. This prospective registry will prove that the selection criteria is accurate and streamlining radioembolization is feasible and safe.

GKL-006 Injection Plus TACE Versus TACE Alone in Patients With Unresectable Hepatocellular Carcinoma

This is a multicenter, randomized, open-label, controlled Phase 2 study in patients with unresectable hepatocellular carcinoma (uHCC). The purpose of this study is to compare the efficacy and safety of GKL-006 Injection in combination with transarterial chemoembolization (TACE) versus TACE alone.

A Study to Assess the Adverse Events and How Intravenously Infused Livmoniplimab in Combination With Budigalimab Moves Through the Bodies of Adult Chinese Participants With Locally Advanced or Metastatic Hepatocellular Carcinoma (HCC)

Hepatocellular carcinoma (HCC) is a common cancer worldwide and a leading cause of cancer-related death. The majority of participants first presenting with HCC have advanced unresectable or metastatic disease. The purpose of this study is to assess adverse events and how livmoniplimab in combination with budigalimab moves through the body in adult Chinese participants with Locally Advanced or metastatic Child-Pugh A Hepatocellular Carcinoma (HCC). Livmoniplimab is an investigational drug being developed for the treatment of HCC. There are 2 stages to this study. Stage 1 is a safety run-in. There are 2 treatment arms in stage 1 and participants will receive escalating doses of Livmoniplimab in combination with budigalimab (fixed dose). Stage 2 is dose expansion. There are 2 treatment arms in stage 2 and participants will receive Livmoniplimab in combination with budigalimab in multiple doses. Approximately 20 adult participants will be enrolled in the study across 15 sites in China. In part 1 (dose escalation), participants will be intravenously infused with escalating doses of livmoniplimab in combination with budigalimab every 3 weeks. In part 2 (dose expansion), participants will be intravenously infused with livmoniplimab in combination with budigalimab in multiple doses every 3 weeks. The estimated duration of the study is up to 2 years. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic and may require frequent medical assessments, blood tests, and scans.

Pragmatic RCT of AI-Assisted Reading for Malignant Hepatic Lesions on CE-CT

The purpose of this multicenter pragmatic randomized controlled trial is to determine whether AI-assisted interpretation of multiphasic liver contrast-enhanced computed tomography (CE-CT) is non-inferior to standard radiology reporting with respect to missed clinically significant malignant focal liver lesions, \*\*with the non-inferiority margin prespecified in the statistical analysis plan before enrollment\*\*, and whether it improves lesion detection, diagnostic characterization, downstream clinical management, and reporting efficiency. On AI-assisted center-days, AI results will be revealed only after the first-line radiologist has saved an unaided initial assessment and may be used to revise the final report. On control center-days, examinations will be interpreted using the standard radiology workflow without access to AI tools.

Streamlined Resin Y90 Radiation Segmentectomy for Small HCC

This single-arm feasibility study evaluating the safety and efficacy of streamlining Yttrium-90 (Y90) radioembolization workflow for patients with small Hepatocellular Carcinoma (\&lt;5cm) that have no aggressive features on baseline imaging. This study aims to recruit N=30 patients prospectively and consolidate the current workflow of 2 days of procedures (1st-day mapping angiography followed by nuclear medicine hepatic lung shunt fraction (LSF) calculation using Tc99-MAA planar and SPECT/CT, and 2nd-day Y90 radioembolization followed by nuclear medicine Y90 SPECT/CT) into 1-day procedure. Several studies have shown that hepatic LSF for HCC tumors smaller than 5cm in the absence of macrovascular invasion and portosystemic shunt placement is invariably \&lt;10%. Therefore, the LSF calculation can be safely omitted from the complex workflow of these patients. This study aims to illustrate that this can be done safely and efficaciously to reduce unnecessary patient travel and healthcare resource utilization. Overall, a total of 30 patients will be included in the study.

Study of Zanzalintinib in Combination With Immuno-Oncology or Other Agents in Participants With Solid Tumors

This is a multicenter Phase 1b, open label, dose-escalation and cohort-expansion study, evaluating the safety, tolerability, pharmacokinetics (PK), preliminary antitumor activity, and effect of biomarkers of zanzalintinib administered alone, and in combination with nivolumab (doublet), nivolumab + ipilimumab (triplet) and nivolumab + relatlimab (triplet) and in combination with docetaxel and prednisone in participants with advanced solid tumors. In addition, the study will evaluate the effect of multiple dose administration of zanzalintinib on the single-dose pharmacokinetics of sensitive CYP3A4, CYP2C9, CYP2C19, or CYP1A2 substrates in participants with advanced solid tumors. In the Expansion Stage, the safety and efficacy of zanzalintinib as monotherapy and in combination therapy will be further evaluated in tumor-specific Expansion Cohorts.

Comparison of the Therapeutic Efficacy of Non-touch Microwave Ablation, Tumor-puncture Microwave Ablation and Surgical Resection for Subcapsular Hepatocellular Carcinoma

Subcapsular hepatocellular carcinoma (HCC) has unique anatomical characteristics that may influence treatment selection and clinical outcomes. Surgical resection and liver transplantation are potentially curative treatments but may be limited by liver function, tumor characteristics, and perioperative risks. Microwave ablation has become an important minimally invasive treatment option for patients with HCC, particularly for lesions that are difficult to treat surgically. This prospective observational cohort study aims to compare the therapeutic efficacy, safety, and long-term outcomes of no-touch microwave ablation, tumor-puncture microwave ablation and surgical resection in patients with subcapsular HCC. Treatment outcomes, including local tumor control, treatment-related complications, recurrence, and survival outcomes, will be evaluated to provide evidence for individualized treatment strategies for patients with subcapsular HCC.

The Safety and Efficacy of Ondansetron in Reducing Immune Checkpoint Inhibitor-Related Toxicities

This study is a prospective, randomized, single-center randomized controlled clinical trial to investigate the safety and efficacy of ondansetron in reducing the toxicity associated with immune checkpoint inhibitor treatment. This study plans to enroll 134 patients with hepatocellular carcinoma who are scheduled to receive standard ICI treatment. This study will adopt the 2023 CSCO Guidelines for the Management of Immune checkpoint inhibitor-related toxicity as the main assessment criterion, and take the incidence and severity of irAEs as the main observation indicators to evaluate the effectiveness of ondansetron in reducing the toxicity related to immune checkpoint inhibitor treatment in patients with hepatocellular carcinoma.

On-treatment Surveillance of Tumor Evolution and Response to Systemic Treatment in Bile Duct and Liver Cancer

The BILLIONSTARS study is a prospective, single arm observational study inviting patients diagnosed with hepatocellular carcinoma (HCC) or cholangiocarcinoma (CCC) who are to be recommended locoregional intervention by surgery, ablation or transarterial chemoembolization and/or antitumoral medical treatment. The aim is to investigate how tumor- and individual-related factors affect response to treatment. To this end, circulating tumor DNA, immune cells and various proteins will be analyzed in repeated blood samples taken before, during and after completion of systemic treatment. When applicable, analyses will also be performed on tumor tissue from resected tumors and biopsies, and in some cases also from autopsies

A Phase 1 Study of the Safety and Tolerability of CTX-10726

This is a Phase 1, open-label, first-in-human study of CTX-10726 monotherapy in patients with metastatic or locally advanced malignancies. The study will be conducted in 2 Cohorts: Cohort 1 Dose Escalation and Cohort 2 Dose Expansion.

TITAN-HCC: Neoadjuvant and Adjuvant QL1706 With TACE in Resectable Hepatocellular Carcinoma Beyond Milan Criteria

This is a single-arm, single-center, prospective trial designed to evaluate the efficacy and safety of transarterial chemoembolization (TACE) combined with ipalimab/tuvonralimab (QL1706) in the peri-operative setting for resectable hepatocellular carcinoma exceeding the Milan criteria, and to explore biomarkers predictive of therapeutic response.

AI-Guided Surveillance and Curative Salvage of Recurrence After Hepatocellular Carcinoma Resection or Ablation

Hepatocellular carcinoma, the most common type of primary liver cancer, can recur after liver resection or thermal ablation performed with curative intent. Follow-up imaging is commonly scheduled at fixed intervals, although the risk of recurrence differs among patients and may change over time. This study will test whether a locked artificial intelligence system can use routinely collected clinical, laboratory, and imaging information to recommend when the next surveillance scan should occur. Adults with no radiological evidence of viable hepatocellular carcinoma after microscopically margin-negative liver resection or complete radiofrequency or microwave ablation will be randomly assigned in a 1:1 ratio to artificial intelligence-guided risk-adapted surveillance or fixed-interval surveillance. In the artificial intelligence-guided group, participants classified as having high, intermediate, or low current recurrence risk will generally undergo the next protocol-scheduled contrast-enhanced imaging examination after 3, 4, or 6 months, respectively. Participants in the control group will undergo protocol-scheduled imaging every 4 months. The risk thresholds are designed so that the expected total number of protocol-scheduled imaging examinations is approximately comparable between the two groups over 24 months. The artificial intelligence system provides surveillance recommendations only. It does not diagnose recurrence, determine eligibility for liver transplantation, or select anticancer treatment. Clinically indicated examinations may be performed at any time in either group. When recurrence is confirmed, participants in both groups will undergo the same protocol-defined multidisciplinary evaluation, and potentially curative-intent treatment may be considered when clinically appropriate. The primary purpose is to determine whether artificial intelligence-guided surveillance increases the probability of being alive at 24 months without having a recurrence that is no longer amenable to protocol-defined curative-intent treatment. The study evaluates the timing and allocation of surveillance rather than an adjuvant anticancer treatment and is not intended to prevent the biological occurrence of recurrence.

Peripheral Blood Biomarkers and Response to Atezolizumab Plus Bevacizumab in Hepatocellular Carcinoma

This single-center prospective observational cohort study aims to evaluate the predictive value of peripheral blood-based biomarkers for treatment response in patients with hepatocellular carcinoma (HCC) receiving first-line atezolizumab plus bevacizumab (T+A) therapy. Residual peripheral blood samples obtained during routine clinical testing will be analyzed without additional blood draws. The study hypothesizes that baseline and longitudinal peripheral blood biomarkers are associated with treatment response and can be used to identify patients more likely to benefit from T+A therapy. Treatment response will be evaluated based on the best overall response (BOR) during treatment. The primary efficacy assessment will be performed according to RECIST 1.1, while modified RECIST (mRECIST) will be used as a supportive assessment. Predictive models based on peripheral blood biomarkers will be developed using RECIST 1.1-defined treatment response as the primary analysis, with mRECIST used for supportive and sensitivity analyses.

The Efficacy and Safety of Donafenib Plus PD-1/L1 Monoclonal Antibodies Plus TACE or HAIC as First-line Treatment for Unresectable Hepatocellular Carcinoma A Multi-center, Retrospective Clinical Study

This is a multicenter, retrospective study planned to enroll patients with unresectable hepatocellular carcinoma (uHCC) who received first-line donafenib combined with an anti-PD-1/L1 monoclonal antibody and either TACE or HAIC at 8 sites between June 1, 2021 and November 30, 2024. The study consists of two cohorts: Cohort A consists of patients who received donafenib + PD-1/L1 inhibitor + TACE, and Cohort B consists of patients who received donafenib + PD-1/L1 inhibitor + HAIC, with a planned enrollment of 200 patients per cohort. Relevant data will be collected to evaluate the efficacy and safety of donafenib combined with an anti-PD-1/L1 monoclonal antibody and either TACE or HAIC in the treatment of uHCC in real-world clinical practice.