Liver Cancer

This study will collect blood from patients with cancer to study the level of cells which decrease the immune response (suppressor cells) before and after chemotherapy. Patients 18 years of age and older with cancer may participate. This study does not involve treatment. Participants will have about 50 ml (3 tablespoonfuls) of blood drawn. Depending on their condition, patients may be invited to enroll in a clinical research study involving chemotherapy, radiotherapy, or surgery. Additional 40-ml blood samples may be drawn during the course of treatment.

This study aims to determine the safety and maximum tolerated dose (MTD) of YMN-136 vaccine through a dose escalation trial, and to investigate whether YMN-136 vaccine can assist in the treatment of patients with advanced hepatobiliary and pancreatic malignancies.

Evaluating the Safety and Efficacy of PD-1 mRNA LNP Vaccine Therapy in Patients with Primary Hepatocellular Carcinoma Who Have Failed Advanced Standard Therapy

The National Liver Cancer Screening Trial is an adaptive randomized phase IV Trial comparing ultrasound-based versus biomarker-based screening in 5500 patients with cirrhosis from any etiology or patients with chronic hepatitis B infection. Eligible patients will be randomized in a 1:1 fashion to Arm A using semi-annual ultrasound and AFP-based screening or Arm B using semi-annual screening using GALAD alone. Randomization will be stratified by sex, enrolling site, Child Pugh class (A vs. B), and HCC etiology (viral vs. non-viral). Patients will be recruited from 15 sites (mix of tertiary care and large community health systems) over a 3-year period, and the primary endpoint of the phase IV trial, reduction in late-stage HCC, will be assessed after 5.5 years.

This is a pilot and feasibility study assessing the role of quantitative multiparametric MRI and blood-based biomarkers for the measurement of liver function in patients receiving radiation therapy for liver cancer, including hepatocellular carcinoma (HCC), cholangiocarcinoma, or liver metastases regardless of primary histology, that are undergoing photon radiation either in the de-novo or re-irradiation setting. The goal of this study is to prospectively evaluate the feasibility of using quantitative multiparametric MRI to monitor liver function at baseline and following liver radiation therapy.

To develop and test liver cancer prevention educational material.

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.

Patients may be considered if the cancer has come back, has not gone away after standard treatment or the patient cannot receive standard treatment. This research study uses special immune system cells called CARE T cells, a new experimental treatment. The body has different ways of fighting infection and disease. No single way seems perfect for fighting cancers. This research study combines two different ways of fighting cancer: antibodies and T cells. Antibodies are types of proteins that protect the body from infectious diseases and possibly cancer. T cells, also called T lymphocytes, are special infection-fighting blood cells that can kill other cells, including cells infected with viruses and tumor cells. Both antibodies and T cells have been used to treat patients with cancers. They have shown promise, but have not been strong enough to cure most patients. Investigators have found from previous research that they can put a new gene (a tiny part of what makes-up DNA and carries a person's traits) into T cells that will make them recognize cancer cells and kill them. In the lab, investigators made several genes called a chimeric antigen receptor (CAR), from an antibody called GPC3. The antibody GPC3 recognizes a protein found solid tumors including pediatric liver cancers. This CAR is called GPC3-CAR. To make this CAR more effective, investigators also added two genes that includes IL15 and IL21, which are protein that helps CAR T cells grow better and stay in the blood longer so that they may kill tumors better. The mixture of GPC3-CAR and IL15 plus IL21 killed tumor cells better in the laboratory when compared with CAR T cells that did not have IL15 plus IL21 .This study will test T cells that investigators made (called genetic engineering) with GPC3-CAR and the IL15 plus IL21 (CARE T cells) in patients with GPC3-positive solid tumors. T cells made to carry a gene called iCasp9 can be killed when they encounter a specific drug called AP1903. The investigators will insert the iCasp9 and IL15 plus IL21 together into the T cells using a virus that has been made for this study. The drug (AP1903) is an experimental drug that has been tested in humans with no bad side-effects. The investigators will use this drug to kill the T cells if necessary due to side effects. This study will test T cells genetically engineered with a GPC3-CAR and IL15 plus IL21 (CARE T cells) in patients with GPC3-positive solid tumors. The CARE T cells are an investigational product not approved by the Food and Drug Administration. The purpose of this study is to find the biggest dose of CARE T cells that is safe, to see how long they last in the body, to learn what the side effects are and to see if the CARE T cells will help people with GPC3-positive solid tumors.

Participants may take part in this study if they are scheduled to undergo a surgery that meets the following: (1) traditional open surgery via laparotomy, (2) length of surgery \>3 hours, and (3) curative-intent surgical resection of a cancer in the stomach, pancreas, bile ducts, liver, or peritoneal surfaces. The purpose of this study is (1) to evaluate the feasibility of collecting blood samples prior to surgery, post-surgery and pre- music-assisted relaxation and imagery (MARI) intervention, and immediately post-MARI intervention and (2) to identify gene expression changes associated with MARI and explore their relationship with immediate changes in pain intensity. Participants will be in this study for the duration of their hospital admission for surgery.

Immune checkpoint inhibitors combined with anti-angiogenic targeted agents have become the first-line standard therapeutic regimen for advanced hepatocellular carcinoma (HCC). Nevertheless, the high incidence rate of therapy-related diarrhea severely impairs patients' quality of life and treatment adherence, and may even result in treatment discontinuation. Current studies mostly focus on symptomatic intervention after diarrhea onset, while few tools are available for upfront risk screening prior to treatment initiation. According to the theory of traditional Chinese medicine (TCM) constitutional types, individuals with different constitutions exhibit discrepant disease susceptibility and drug responses. Based on a prospective cohort design, this study aims to explore the correlation between TCM constitutional types and immune-targeted therapy-related diarrhea in HCC patients, and further construct a risk prediction model integrated with both western medical and TCM indicators. This study is designed as a multicenter prospective observational cohort study. A total of 350 primary HCC patients receiving combined immunotherapy and targeted therapy at the Affiliated Hospital of Chengde Medical University from January 2027 to December 2028 will be enrolled into the model development cohort. Another 150 patients from Chengde Central Hospital and Chengde Hospital of Traditional Chinese Medicine between January 2029 and January 2030 will be recruited as the external validation cohort. Baseline data will be collected before treatment, including sociodemographic and general clinical information, tumor and treatment-related data, laboratory test results, TCM constitutional assessment, nutritional risk screening, physical function and psychological status evaluation. All participants will be followed up regularly for one year to record the occurrence of diarrhea. Samples in the development cohort will be randomly divided into a training set and an internal validation set at a stratified ratio of 7:3. Lasso regression will be applied to screen predictive factors, and multivariate Logistic regression will be adopted to establish a nomogram prediction model. Receiver operating characteristic (ROC) curves, calibration curves and decision curve analysis (DCA) will be used to assess the discrimination, calibration and clinical net benefit of the established model, respectively. The independent multicenter data of the external validation cohort will adopt consistent variable criteria, outcome definitions and the prediction model from the development cohort to evaluate the cross-center generalizability, stability and clinical applicability of the model for comprehensive efficacy verification. The study protocol has been approved by the Medical Ethics Committee of the Affiliated Hospital of Chengde Medical University. Written informed consent will be obtained from all subjects before enrollment. The research findings will be disseminated via academic journal publications, web-based assessment tools and clinical promotion. The established TCM constitution risk screening tool can be directly applied to routine admission assessment in the hepatology department.

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

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide and is frequently diagnosed at an advanced stage, resulting in limited therapeutic options. Despite the advances in immunotherapy, a substantial proportion of patients fail to respond adequately due to mechanisms of immune resistance. The gut microbiota plays a crucial role in modulating the response to immune checkpoint inhibitors (ICIs), and fecal microbiota transplantation (FMT) has demonstrated the ability to enhance their efficacy in other tumors, such as melanoma. In patients with HCC and cirrhosis, intestinal dysbiosis, characterized by a reduction in beneficial bacteria (e.g., Bifidobacterium, Akkermansia) and increased inflammation, is associated with an immunosuppressive profile. Furthermore, a dysbiosis index has been correlated with response to ICIs. In this context, FMT represents a promising strategy to enhance the efficacy of immunotherapy in HCC, although data regarding its efficacy and safety are still limited.

Radiofrequency devices have been increasingly employed in liver surgery in order to achieve proper hemostasis and this use has become more evident with the implementation of minimal invasive surgery. Due to its well-known efficacy for tumor ablation (i.e. hepatocarcinoma) it use has been extended in some cases to ablate the liver surface after resection in questionable resection. Till date, despite the majority of surgeons apply an additional coagulation in doubtful margins, there is not an evidence that this maneuver really decreases the local recurrence or increases the overall survival. On the contrary, some studies have suggested that non-anatomical resections in order to spare liver parenchyma could lead to major zones of liver ischemia in the remnant liver and thus favoring recurrence. However, major liver ischemia (defined as grade 2 o more) is unlikely to be provoked by 1 cm-depth additional coagulation of the margin. The investigators previously published in a retrospective study the concept of additional margin coagulation within liver resections and narrow margins and demonstrated that the study group had significantly less local recurrence compared to the controls. Therefore, in the present study the aim is to continue this evaluation through a multicenter randomized clinical trial.

This is a master protocol for a prospective Phase I-II study evaluating feasibility and efficacy of incorporating magnetic resonance imaging (MRI) simulation into the planning of radiation treatments.

The DRAGON registry aims to collect data on combined portal and hepatic vein embolization (PVE/HVE) for liver tumors, a technique expected to enhance liver regeneration compared to standard PVE. This collaborative registry focuses on identifying associations between baseline clinical/imaging parameters, clinical outcomes, and safety for patients undergoing PVE/HVE.

This is a phase 2a, randomized, double-blinded, placebo-controlled pilot clinical trial determining the impact of riluzole therapy on circulating brain derived neuropathic factor (BDNF) levels in cancer survivors (recently completing prior treatment regimens) or patients who have received whole brain radiation for benign or malignant tumors with cancer related cognitive impairment.

The objective of this study is the acquisition of whole blood samples and serum samples from participants with untreated Hepatocellular Carcinoma (HCC) and subjects undergoing Hepatocellular Carcinoma (HCC) surveillance. These samples will be used for research purposes to develop and validate the Helio multi-analyte blood test.

Second Life Therapeutics is developing SL-28, an allogeneic, non-genetically modified cell-based therapy for the treatment of advanced solid tumours. The company has recently demonstrated a novel, non-genetic approach to modulate immune cell activity through targeted manipulation of the Universal Receptive System. The purpose of this open label, multi-center clinical trial is to evaluate the anti-tumor activity, safety, and pharmacokinetics, single-agent SL-28 in patients with a diverse array of solid tumors. The study includes an initial Phase 1 dose escalation to determine recommended dose(s) for expansion of SL-28 as a monotherapy and Phase 2 expansion cohorts. The study will enroll patients with advanced solid tumours, including those who failed previous lines of chemo- and immunotherapies.

This study will evaluate whether a precision navigation intervention can help community residents at high risk for cancer complete recommended cancer screening. The study will be conducted in communities participating in an urban cancer screening program in China. Eligible participants will be adults aged 45 to 74 years who are permanent residents of participating communities and have been identified as being at high risk for at least one of five cancers: lung cancer, breast cancer, colorectal cancer, upper gastrointestinal cancer, or liver cancer. Participants must not have completed the corresponding free clinical screening before enrollment. This is a dual-cohort, cluster randomized controlled trial. Communities, rather than individual participants, will be assigned to one of three groups: a precision navigation group, a usual health education group, or a waiting control group. Participants will be classified into two cohorts according to the number of cancers for which they are assessed as high risk. Cohort A will include participants at high risk for three or more cancers, and Cohort B will include participants at high risk for one or two cancers. Participants in the precision navigation group will receive a personalized navigation report matched to their risk profile. The report will explain the screening tests most relevant to them, help them understand screening choices, and provide practical steps to support screening completion. Participants in the usual health education group will receive general cancer screening education materials. Participants in the waiting control group will not receive active screening promotion during the main intervention period, but will receive general education materials after the primary assessment. The main outcome is whether participants complete the recommended cancer screening during follow-up. The study will also assess changes in screening-related decision conflict, anxiety, self-efficacy, and behavioral intention. The results may help improve community-based cancer screening programs and provide evidence for using personalized navigation strategies to increase screening participation among high-risk populations.

Open-label, dose escalation, multi-center, Phase I/II clinical trial to assess the safety/tolerability and determine the recommended Phase II Dose (RP2D) of ET140203 T-cells in pediatric subjects who are AFP-positive/HLA-A2-positive and have relapsed/refractory HB, HCN-NOS, or HCC.

Purpose: This phase II clinical trial evaluates whether a combination of liver-directed local therapies (HAIC and DEB-TACE) with immunotherapy (toripalimab) and targeted therapy (lenvatinib) is safe and effective for patients with unresectable intrahepatic cholangiocarcinoma (a type of liver cancer that cannot be removed by surgery). Participants: Adults aged 18-85 years with pathologically confirmed unresectable intrahepatic cholangiocarcinoma, no prior immune checkpoint inhibitor therapy, and adequate organ function. Study details include: Study Duration: Up to 24 months per participant Treatment Duration: Up to 6 cycles (each cycle is 21 days) of combination therapy, followed by maintenance therapy with toripalimab and lenvatinib until disease progression or unacceptable toxicity Visit Frequency: Every 3 weeks during the treatment phase; tumor imaging assessments every 6-8 weeks Primary endpoints: Objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Safety will be assessed by monitoring adverse events graded according to NCI-CTCAE v5.0. Toripalimab and lenvatinib are not available through an expanded access program.

This study will collect tumor specimens with correlated clinical and demographic data from patients who are undergoing a biopsy or similar procedure to obtain tumor tissue as a normal course of their medical management or diagnostic work-up for suspected or confirmed cancer.

The iCaRe2 is a multi-institutional resource created and maintained by the Fred \& Pamela Buffett Cancer Center to collect and manage standardized, multi-dimensional, longitudinal data and biospecimens on consented adult cancer patients, high-risk individuals, and normal controls. The distinct characteristic of the iCaRe2 is its geographical coverage, with a significant percentage of small and rural hospitals and cancer centers. The iCaRe2 advances comprehensive studies of risk factors of cancer development and progression and enables the design of novel strategies for prevention, screening, early detection and personalized treatment of cancer. Centers with expertise in cancer epidemiology, genetics, biology, early detection, and patient care can collaborate by using the iCaRe2 as a platform for cohort and population studies.

Major visceral oncologic surgery is associated with high postoperative morbidity, prolonged hospitalization, delayed recovery, and reduced quality of life. Patients undergoing surgery of the pancreas, liver, bile ducts, stomach, or esophagus frequently present with reduced physical fitness, malnutrition, sarcopenia, and psychological distress, all of which may negatively affect surgical outcomes and rehabilitation. Although prehabilitation has shown potential to improve functional capacity before surgery, structured prehabilitation pathways are currently not routinely implemented in Austria, and the feasibility of digitally supported perioperative care pathways remains insufficiently evaluated. The aim of the Prehab2Rehab-OncoVis study is to evaluate the feasibility, acceptability, and safety of a multimodal, digitally supported prehabilitation intervention for patients undergoing major visceral oncologic surgery with curative intent. The study will additionally explore potential effects on clinical recovery, functional capacity, rehabilitation outcomes, and patient-reported outcomes across the perioperative pathway. Prehab2Rehab-OncoVis is designed as a prospective, single-arm feasibility cohort study conducted at the University Hospital Salzburg and the University Institute of Sports Medicine, Prevention and Rehabilitation, coordinated by the Paracelsus Medical University in cooperation with the Ludwig Boltzmann Institute for Rehabilitation Research and the Ludwig Boltzmann Institute for Digital Health and Prevention within the Prehab2Rehab consortium. Approximately 30 adult patients, with the possibility to include up to 50 participants if feasible, will be consecutively recruited. The intervention consists of a four-week multimodal prehabilitation program combining supervised exercise training, promotion of physical activity, nutritional counseling, psycho-oncological distress screening, and health literacy support. Digital tools will support the intervention throughout the perioperative pathway, including the HERO application (Das Herz Reha-Informationstool) for patient education and health literacy, aktivplan as a digital exercise planner and training diary, and the CAATS telecommunication platform for remote supervision and tele-prehabilitation sessions where appropriate. The exercise intervention includes supervised center-based sessions and, for participants with longer travel distances, a hybrid model combining center-based and tele-prehabilitation sessions. Nutritional counseling will follow current European Society for Clinical Nutrition and Metabolism (ESPEN) guidelines and includes screening for malnutrition risk. Psycho-oncological distress screening will follow recommendations of the German Cancer Society and includes referral to supportive care when clinically indicated. Participants will be assessed throughout the perioperative pathway, including at the beginning and end of prehabilitation (Prehabilitation Assessment 1 \[PRE1\] and Prehabilitation Assessment 2 \[PRE2\]), during hospitalization and rehabilitation, and at a three-month follow-up after surgery. Primary outcomes focus on feasibility, including recruitment and retention rates, adherence, fidelity, safety, data management feasibility, and acceptability and usability of the digital technologies. Secondary outcomes include clinical recovery indicators, postoperative complications, length of hospital and intensive care stay, functional independence, psychological well-being, quality of life, body composition, cardiorespiratory fitness, functional exercise capacity, and muscle strength. To contextualize outcomes, two historical comparator cohorts will be used: a local hospital cohort of patients who previously underwent similar surgery without prehabilitation, and a national rehabilitation cohort derived from routine rehabilitation datasets matched for diagnosis, sex, and age. The study is intended to generate feasibility data and preliminary estimates that may support the development of future adequately powered randomized controlled trials evaluating digitally supported prehabilitation and rehabilitation pathways in visceral oncologic surgery.

This prospective clinical study will examine the ability of contrast-enhanced ultrasound (CEUS) to assess the treatment response of hepatocellular carcinoma (HCC) to transarterial radioembolization (TARE). HCC is the third leading cause of cancer mortality worldwide and the single fastest growing cause of cancer mortality in the United States. TARE is recommended for 15-25% of HCC patients. Treatment response is generally evaluated using contrast-enhanced CT or MRI 1-2 months and 4-6 months post-TARE. Although TARE is an effective therapy, assessment of treatment response using CT/MRI is challenging because CT/MRI frequently diagnoses tumor response as equivocal or non-progressing for up to 6 months post-TARE based on LI-RADS criteria. This delay in diagnosing tumor viability subsequently delays needed retreatment and can even serve as a barrier to transplantation. Our prior work in HCC locoregional therapy has shown CEUS provides improved sensitivity in detecting viable tumor following transarterial chemoembolization relative to traditional CT/MRI. Therefore, the investigators propose to evaluate both qualitative and quantitative CEUS as a tool for evaluating HCC post-TARE at similar time points of clinically recommended cross-sectional imaging, while also investigating the role of Kupffer phase imaging. The investigators plan to enroll a total of 30 patients scheduled for TARE of a treatment naïve HCC over an 18-month period, allowing for a minimum of 6 months follow up. Patients will undergo a CEUS examination within two weeks of their first two clinically indicated CT/MRI exams (obtained at Jefferson 1-2 months and 4-6 months post TARE). In patients retreated prior to their 4-6 month MRI, CEUS may also be performed in the absence of the MRI at this time point but prior to retreatment. Patients will be recruited across six major hospitals within the Jefferson Health Enterprise. Those eligible for participation will be identified by project co-investigators and contacted by the study coordinator to discuss participation and to explain the study. The patient will be given time to consider the risks and benefits of the study and ask questions about participation. If agreeable, the patient will then arrange with the project coordinator to come to Jefferson's center city campus to sign consent and take part in the research study.