Clinical Research Directory

Utilize Imaging to Assess Changes in Hepatocellular Carcinoma Perfusion as Potentiated by Intra-Arterial Nitroglycerin

This is a single-arm, open-label, single-center, first-in-human feasibility study evaluating parenchymal blood volume (PBV) imaging as a tool to dynamically assess perfusional changes in hepatocellular carcinoma (HCC) potentiated by intra-arterial administration of nitroglycerin.

Continuation of First-line Therapy With Radiotherapy Versus Early Switch to Second-line Therapy in Oligoprogressive HCC

This multicenter, prospective, randomized, controlled, open-label, two-arm Phase III clinical trial is designed to evaluate whether adding radiotherapy to oligoprogressive lesions while continuing first-line systemic therapy at the time of oligoprogression can effectively prolong progression-free survival compared to early switching to second-line systemic therapy in oligoprogressive hepatocellular carcinoma.

STRATHEP: AI-Driven Treatment Stratification for Advanced Hepatocellular Carcinoma

STRATHEP develops and validates a multimodal AI model to predict treatment response in advanced hepatocellular carcinoma. By integrating digital pathology and MRI radiomics, the project identifies patients likely to benefit from modern systemic therapies, using the RECIST 1.1 framework as the primary benchmark.

Phase 1 Trial of ACE723, A Dual-Payload Antibody Drug Conjugate, in Patients With Advanced HCC Who Have Failed or Progressed on Standard Systemic Therapy Containing ICIs

ACE723 is a dual-payload antibody drug conjugate targeting glypican-3 (GPC-3) that is under investigation for the treatment of unresectable or metastatic hepatocellular carcinoma (HCC).

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.

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.

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

NK521 in the Treatment of Advanced Solid Tumors

Eligible subjects with advanced hepatocellular carcinoma and ovarian cancer will be divided into two treatment groups based on the volume of ascites. Group A consists of patients with mild ascites, who will receive NK521 via intravenous infusion. Group B includes patients with moderate to severe ascites, who will be treated with investigator-selected systemic regimens combined with intraperitoneal perfusion of NK521. Systemic and local medications will be administered in accordance with the treatment regimens of respective groups, and the safety of the study drug will be monitored. Preliminary anti-tumor efficacy will be assessed using the RECIST 1.1 criteria at Week 6 after the first infusion of NK521. Catheter placement and ascites drainage will be performed 3 days prior to the first intraperitoneal perfusion of NK521. After the initial intraperitoneal perfusion treatment, the therapeutic effect on ascites will be evaluated per the WHO criteria for ascites assessment.

Hyperpolarized 13C-MRI in Patients With Hepatocellular Carcinoma Undergoing Radiotherapy, Atezolizumab, and Bevacizumab

Increased pyruvate-to-lactate conversion is a hallmark of HCC metabolism. In parallel, activation of pro-inflammatory immune cells triggers a metabolic switch towards anaerobic glycolysis. Hyperpolarized carbon-13 (13C) pyruvate MRI is a state-of-the-art non-invasive imaging method that offers real-time insights into tissue metabolism. Recent studies have demonstrated its promising potential in predicting responses to radiotherapy and immunotherapy in solid tumors, given the significance of pyruvate as a downstream metabolite in glycolysis. However, its application in assessing treatment response in hepatocellular carcinoma (HCC) patients remains unclear. The establishment of quantitative imaging biomarkers for predicting responses to radio-immunotherapy is an unmet need in the management of HCC patients. While radiotherapy (RT) effectively controls localized tumors through the induction of unrepairable DNA double-stranded breaks (DSBs) and cell death, its therapeutic efficacy on distal, non-irradiated tumor cells is limited, with out-of-field recurrence being a common pattern of failure in HCC patients treated with high-dose irradiation. Atezolizumab (anti-programmed death-ligand 1; anti-PD-L1) in conjunction with bevacizumab (anti-vascular endothelial growth factor; anti-VEGF) has recently emerged as the standard first-line systemic treatment for unresectable hepatocellular carcinoma (HCC). Despite an objective response rate (ORR) of only 27%, the majority of patients succumb to HCC progression and liver failure. Our preclinical study (Hsieh et al., Science Immunology 2022) uncovered that RT, when combined with PD-L1/PD-1 blockade, induces immunogenic cell death and tumor antigen cross-presentation in antigen-presenting cells, enhancing systemic antitumor T cell responses in murine tumor models. Recent retrospective cohorts suggest that RT targeting all hepatic tumors combined with PD-L1/programmed death-1 (PD-1) blockade is associated with an improved ORR and median progression-free survival (PFS) in patients with unresectable HCC, demonstrating a favorable safety profile. The synergistic antitumor effects of this combination therapy with RT, atezolizumab, and bevacizumab have led to its increasing adoption in routine clinical practice. This phase II non-randomized trial aims to prospectively investigate the predictive value of hyperpolarized 13C-MRI, along with comprehensive metabolomics and radiomics analyses, for immune response assessment including tumor control outcomes and toxicity in patients with HCC undergoing radiotherapy, atezolizumab, and bevacizumab.

Study of the Theranostic Pair RYZ811 (Diagnostic) and RYZ801 (Therapeutic) to Identify and Treat Subjects With GPC3+ (Glypican-3) Unresectable HCC

Phase 1/2 randomized, controlled, open-label trial of theranostic pair RYZ811 (diagnostic) and RYZ801 (therapeutic) to identify and treat subjects with GPC3+ unresectable hepatocellular carcinoma (HCC)

Assessment of Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of GKL-006 Injection in Combination With TACE in Unresectable Hepatocellular Carcinoma

This Phase Ia study evaluated the safety and tolerability of a single escalating dose via intravenous infusion of the autologous invariant natural killer T cells (iNKT-cell) product GKL-006 in combination with transarterial chemoembolisation (TACE) in participants with unresectable hepatocellular carcinoma (uHCC). The study aimed to characterise dose-limiting toxicities (DLT), determine the maximum tolerated dose (MTD), and assess pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antitumour activity.

Multimodalomics-based Construction of Spatiotemporal Characteristics of Dynamic Liver Cancer Microenvironment to Characterize the Clinical Application of Immune Mechanisms in Liver Cancer

This study aims to explore whether adding an additional MRI sequence to routine liver scans can better characterize the immune microenvironment of liver cancer. We plan to prospectively enroll patients diagnosed with or suspected of having liver cancer who undergo routine MRI examinations. In addition to the standard MRI protocol, participants will receive one extra MRI sequence. We will analyze the imaging features from this additional sequence and combine them with clinical data to construct a multi-omics model. The goal is to identify imaging biomarkers that can reflect the dynamic changes of the tumor microenvironment, which may help improve the diagnosis and clinical management of liver cancer.

TACE in Combination With Tislelizumab and Lenvatinib for Advanced HCC (CHANCE2602)

The purpose of this study is to evaluate the safety and efficacy of transarterial chemoembolization (TACE) in combination with Tislelizumab and Lenvatinib in patients with advanced-stage hepatocellular carcinoma (HCC).

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)

A US Study to Evaluate Transarterial Radioembolization (TARE) in Combination With Durvalumab and Bevacizumab Therapy in People With Unresectable Hepatocellular Carcinoma Amenable to TARE

The purpose of this study is to measure the efficacy and safety of durvalumab intravenous (IV) solution plus bevacizumab IV solution after transarterial radioembolization (Yttrium 90 glass microspheres TARE) in participants with unresectable hepatocellular carcinoma (HCC) amenable to embolization.

Radiation Therapy Followed by Durvalumab (MEDI4736) and Tremelimumab And Surgery Versus Radiation Therapy Followed by Surgery for Resectable Hepatocellular Carcinoma.

The objectives of this study is to estimate the biological activity of combination chemotherapy and radiation versus radiation alone in patients with Hepato Cellular Carcinoma (HCC). The study hypothesizes is that combination chemotherapy and radiation is superior to radiation alone in inducing a biological response. The study hypothesizes that combination chemotherapy and radiation is superior to radiation alone in inducing a biological response. A biological response, or change in the tumor microenvironment (TME), is defined by reduced infiltration of intra-tumoral regulatory T cells (Tregs), a decrease in tumour-associated macrophages (TAMs) of the M2 phenotype, and an increase in immune cells such as effector CD8+ T-cells. An increased rate of biological response is therefore expected in participants receiving the combination of Durvalumab, Tremelimumab, and stereotactic body radiation therapy (SBRT), compared to those receiving SBRT alone. Additionally, biological response is hypothesized to correlate with pathological response. The study has been conducted within a WOO window of opportunity randomized clinical trial in order to obtain data in the quickest and safest manner. Patients undergoing surgery are very healthy by definition and will be able to tolerate treatment without any major complications, leading to adequate tissue samples before and after treatment.

Breath Research Narrow Validation for Gastrointestinal Cancer Detection

The investigators of this study are developing a simple breath test to help detect gastrointestinal (gut) cancers earlier, including cancers of the oesophagus (food pipe), stomach, pancreas, liver and bowel. These cancers often cause non-specific symptoms that are similar to benign conditions, making early diagnosis difficult. Delays between the onset of symptoms and referral for a diagnostic test such as an endoscopy or a scan, can allow the cancer to progress. The breath test detects small molecules called volatile organic compounds (VOCs) that are released in exhaled breath. Some of these VOCs are strongly associated with these cancers and may help identify high-risk patients who require urgent investigation. In practice, patients who come to their GP with concerning symptoms will be offered the breath test. If the test is positive, patients can be referred promptly for a diagnostic test, while those with a negative result can be reassured and offered re-testing if symptoms persist. Earlier diagnosis could improve access to curative treatment while reducing unnecessary invasive investigations. Previous studies have identified a panel of VOCs that appear to distinguish patients with gastrointestinal cancers from those without cancer. This study aims to confirm these findings in a new group of participants to determine whether the same biomarkers can be reliably identified. Participants will provide a breath sample, usually before a hospital procedure they are already scheduled to undergo, and complete a short questionnaire about their medical history and medications. Some participants will also be asked to drink a nutritional supplement before providing a second breath sample. The results will help determine whether the breath test is reliable enough for further clinical evaluation

GPC3-Targeted PET/CT in Hepatocellular Carcinoma

The objective of the study is to evaluate the diagnostic value of GPC3-targeted PET/CT in patients with suspected or histologically/clinically confirmed hepatocellular carcinoma, and to compare with contrast-enhanced MRI.

GPC3-Targeted PET Imaging of 18F-X12 in Hepatocellular Carcinoma

This is a diagnostic study. This clinical trial aims to evaluate the diagnostic performance and safety of the novel radiotracer 18F-X12 in patients with hepatocellular carcinoma (HCC), and to provide evidence supporting a new approach for its early diagnosis, accurate staging and recurrence assessment.

PULSAR Combined With Fecal Microbiota Transplantation for Advanced Hepatocellular Carcinoma Progressing After First-Line Targeted-Immunotherapy

This is an open-label, multicenter, randomized controlled Phase II trial. Patients with advanced hepatocellular carcinoma (HCC) who developed secondary resistance to first-line targeted-immunotherapy were randomly assigned to receive either the original first-line targeted-immunotherapy combined with FMT and PULSAR (experimental group), or second-line targeted-immunotherapy (control group). The first-line targeted-immunotherapy regimens consisted of tislelizumab combined with one of the first-line evidence-based tyrosine kinase inhibitors (TKIs), including lenvatinib, donafenib, apatinib, and sorafenib. Given that this study enrolled patients who progressed after an initial response to first-line targeted-immunotherapy, the second-line regimen in the control group continued tislelizumab immunotherapy while switching the TKI to regorafenib, an agent with second-line evidence.

Registry of Minimally Invasive Cancer Treatment Using Spectral Angio-CT Image Guidance

This study collects data from patients undergoing minimally invasive, image-guided cancer treatments at participating hospitals in the Netherlands and France. All treatments are performed as standard clinical care and include procedures such as tumor ablation and catheter-based treatments of cancer in the liver, kidney, lung, and bone. During these procedures, a spectral angio-CT system is used for image guidance. This advanced CT scanner automatically captures additional imaging information beyond what is used in routine clinical decision-making. The goal of this study is to investigate how this additional imaging information is associated with treatment outcomes, and how it can be used in the future to improve treatment planning, procedural guidance, and prediction of treatment results. No experimental interventions are performed. Participation does not alter the treatment or follow-up patients receive. Data are collected from medical records and imaging systems and stored securely for analysis.

SBRT Versus Surgical Resection for Small HCC

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related incidence and mortality in China and represents a major public health challenge. Surgical resection is the most commonly used curative treatment for HCC and can provide favorable long-term outcomes. However, resection is associated with substantial perioperative morbidity, and its applicability is limited in certain patient populations, including those with recurrent disease, those who have undergone conversion therapy, and those with significant coexisting medical conditions. Advances in radiotherapy technology and the development of highly precise delivery techniques have led to the increasing use of stereotactic body radiotherapy (SBRT) in the management of HCC, particularly in patients with small tumors. Randomized controlled trials conducted by our group have shown that, in patients with recurrent small HCC, SBRT provides superior local tumor control compared with radiofrequency ablation. These findings suggest that SBRT may represent a potentially curative treatment option for selected patients with small HCC. On the basis of this evidence, the present study is designed to compare the efficacy and safety of surgical resection and SBRT in patients with small HCC. Patients with a solitary tumor measuring 5 cm or less in maximum diameter will be randomly assigned to undergo either surgical resection or SBRT. The primary end point of the study is overall survival. This trial aims to define the relative benefits and risks of these two treatment strategies and to provide high-quality evidence to inform clinical decision making and future guideline recommendations.

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.

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.