Clinical Research Directory

Advanced Therapies for Liver Metastases

Liver metastases (MTS) are the main cause of death for patients affected by colorectal carcinoma (CRC) and pancreatic ductal adenocarcinoma (PDAC), thus representing the major unmet clinical need for these malignancies. Based on preliminary and published data, the investigators hypothesize that innovative immune, gene, and cell therapy approaches might overcome the tolerogenic liver microenvironment and represent powerful therapeutic tools for liver MTS of PDAC and CRC. The investigators have therefore planned an observational clinical study to enroll distinct cohorts of patients (i.e., metastatic CRC, preneoplastic, metastatic, and non-metastatic PDAC) and finely characterize, through integrated state-of-the-art -omics, the immune and non-immune microenvironment of their primary tumor and/or liver metastases as well as correlate changes in the activation status and phenotype of peripheral blood leukocytes. Healthy volunteers will be enrolled as negative controls. The investigators aim at identifying: i) actionable tumor-associated antigens (TAAs) and local immune suppressive and regulatory pathways; ii) biological parameters for early diagnosis of relapse; iii) the effect of therapies on the shaping of anti-tumor immune responses. Data collected will be instrumental for the generation of novel advanced therapy medicinal products (ATMPs). Indeed, this protocol is part of a multi-partner translational program, supported by the AIRC 5 per Mille 2019 grant, focused on the development, validation, and implementation of clinical testing for ATMPs to ameliorate the cure of CRC and PDAC, and possibly to help the study of other solid tumors. Moreover, the systematic and long-term follow-up of enrolled patients will possibly point to early predictors of differential prognosis and patients' categories eligible for tailored therapies, including those with the novel ATMPs. In this regard, two additional substudies were incorporated into the main LiMeT protocol in July 2024 and January 2026, respectively, supported by supplementary funding: 1) the TREATLIVMETS (Treating Liver Metastasis) project, funded by the European Research Council (ERC) under the Horizon Europe research and innovation program; 2) the "Deciphering and targeting the immunological niche in PDAC" project, funded by the Fondazione Regionale per la Ricerca Biomedica (FRRB) under the "From Bed to Bench 2024" call. In the latter substudy, machine learning will be integrated with the spatial multi-omic profiling of the immune landscape in preneoplastic and neoplastic lesions in a subset of IPMN and PDAC patients, supporting the discovery of new therapeutic targets and enabling the early detection of preneoplastic lesion progression.

LDRT Combined With Immunochemotherapy for Colorectal Cancer With Liver Metastasis

In recent years, growing evidences have demonstrated promising synergistic antitumor effects of radiotherapy combined with immunotherapy. More over, LDRT may enhance the antitumor effect of immunotherapy by altering the tumor immune microenvironment (TIME) and adjusting the immune response. In this study, we will explore the safety and feasibility of LDRT and immunochemotherapy in liver metastatic colorectal cancer. 9-18 participants will be enrolled in this study. All will take part at Daping Hospital, Army Medical University.

Scout Dose of Resin Microspheres

This study looks at a liver cancer treatment called radioembolization and tests a new, possibly more accurate way to check if the treatment is safe for a patient's lungs. Radioembolization is a procedure where tiny beads containing a radioactive substance (yttrium-90) are injected into the arteries that feed a liver tumor. These beads lodge mainly in the tumor and deliver radiation directly to it, while sparing most of the normal liver. However, some of these beads can bypass the liver circulation and travel to the lungs. If too many reach the lungs, they can cause serious radiation damage called radiation pneumonitis. To avoid this, doctors currently perform a "test run" before the real treatment. They inject a different particle called MAA into the liver artery and then do nuclear medicine scans to see how much of it goes to the lungs versus the liver. This percentage is called the lung shunt fraction. If the lung shunt is 20% or higher, radioembolization is not done; if it is between 10% and 20%, the decision depends on tumor size. The actual treatment usually happens 1-2 weeks after this test. MAA particles are similar in size to the treatment beads but not identical; some are smaller. Because of this, MAA may slightly overestimate how much of the treatment dose would really go to the lungs. Also, MAA is fully imported and has had periods of supply problems worldwide. For these reasons, there is a need for another, more accurate and more reliable way to measure lung shunt. The LASER study tests an approach called a "scout dose." In this method, doctors take a small amount of the actual treatment beads (SIR-Spheres, a resin yttrium-90 microsphere product) and inject a low radioactive dose (0.56 GBq) into the liver artery on the day of treatment. They then perform a PET/CT scan and calculate how much of this scout dose went to the lungs and how much stayed in the liver. Because the scout dose uses the same type of beads as the real treatment, it may give a more accurate picture of the true lung shunt. The study will enroll 30 adult patients who have liver tumors (liver cancer, intrahepatic cholangiocarcinoma, or liver metastases) and are already scheduled to receive radioembolization. All participants must have good liver function (Child-Pugh A), good performance status (ECOG 0-1), and an MAA-based lung shunt fraction below 20%. They also need to meet standard blood test criteria and have a life expectancy of at least three months. Each patient first undergoes the usual work-up: liver artery angiography, MAA injection, and nuclear scans, which are used to plan the treatment dose. One to two weeks later, on the treatment day, the patient has another angiogram, receives the 0.56 GBq scout dose into the liver artery, and has a scout PET/CT scan while the catheter is kept in place. After calculating the lung shunt from the scout dose, the patient is brought back to the angiography room and receives the planned treatment dose, reduced by the amount already given as the scout dose. The next morning, a treatment Y90 PET/CT scan is performed. The main measurement of interest is the lung shunt fraction calculated three different ways: from the initial MAA scan, from the scout Y90 PET/CT, and from the treatment Y90 PET/CT. The researchers will compare how closely these three values agree. They will also look at how much radiation the tumor and normal liver receive (tumor dose, normal liver dose) and the radiation dose to the lungs, again using all three imaging methods. Patients will be followed for one year with regular clinic visits, blood tests, and CT or MRI scans according to usual care. The study will carefully record side effects such as fatigue, pain, poor appetite, and more serious problems like liver failure or radiation pneumonitis, and grade them using a standard international system (CTCAE v5.0). The researchers expect that adding the scout dose and extra scan will lengthen the procedure by about two hours and cause some discomfort from lying down longer, but they do not expect a major increase in serious risks compared with standard treatment. By the end of the study, the team aims to show whether the scout dose method can safely and accurately replace or complement the traditional MAA-based test. If successful, this could improve the precision of radioembolization planning and offer a reliable alternative when MAA is not available

NH002-mediated Sonoporation With Chemotherapy in Advanced Pancreatic Cancer

This is a phase I study that will enroll patients with pancreatic cancer and liver metastasis who have failed prior gemcitabine-based chemotherapy. Patients will be treated with nanoliposomal irinotecan plus 5-FU and leucovorin and NH002-based sonoporation to the liver metastasis.

A Clinical Trial of Envafolimab Combined With Lenvatinib for Kidney Cancer With Liver Spread

This is an open-label, single-arm, prospective, multicenter clinical study designed to evaluate the efficacy and safety of envafolimab in combination with lenvatinib for the treatment of patients with clear cell renal cell carcinoma (ccRCC) accompanied by liver metastases. The Department of Urology at Fudan University Shanghai Cancer Center serves as the primary research center.

Hyperthermia Combined With Immune Checkpoint Inhibitors in the Treatment of Advanced Gastrointestinal Malignancies With Liver Metastases

This study aims to explore the synergistic antitumor effects and safety of hyperthermia combined with immune checkpoint inhibitors (ICIs) in patients with advanced gastrointestinal malignancies with liver metastases. Liver metastasis represents a common cause of treatment failure in gastrointestinal cancers, and the response rate to ICIs remains suboptimal in certain patients with liver metastases, potentially attributable to the immunosuppressive hepatic microenvironment. The combination of hyperthermia with ICIs, chemotherapy, or other therapeutic modalities may further enhance treatment efficacy. Hyperthermia could potentially reverse immunosuppression and improve ICI effectiveness through mechanisms including enhanced tumor blood perfusion, promoted antigen presentation, and increased immune cell infiltration. This multicenter, open-label, dual-cohort phase II trial will evaluate patients stratified by tumor type (colorectal cancer versus gastric cancer) to assess the objective response rate (ORR), progression-free survival (PFS), and safety profile of hyperthermia-ICI combination therapy. Concurrently, dynamic monitoring of peripheral immune markers (such as neutrophil-to-lymphocyte ratio and interleukins) and tumor microenvironment alterations will be conducted to identify potential predictive biomarkers, thereby providing preliminary evidence for subsequent phase III investigations. The ultimate objective is to develop more effective combination treatment strategies for patients with advanced gastrointestinal malignancies accompanied by liver metastases.

Fruquintinib Combined With Sintilimab ± Radiotherapy for Third-line Treatment of Colorectal Cancer With Liver Metastases

Colorectal cancer (CRC) is a significant cause of morbidity and mortality worldwide. Its early clinical manifestations are often subtle, leading to late-stage diagnosis in about 30% of cases with distant metastases. Liver metastases are widespread and associated with poor prognosis, especially in terms of response to immunotherapy. This prospective study will evaluate the efficacy of combined therapy involving sintilimab, fruquintinib, and radiotherapy in CRC with liver metastases. The primary objectives are to assess progression-free survival, overall survival, and treatment response rates. This study aims to provide valuable insights into optimizing third-line and subsequent therapies for CRC with liver metastases by elucidating the efficacy and safety of this combined treatment approach.

Intra-tumoral (IT) Injection of vvDD-hIL2-2-RG-1 for Metastatic Gastrointestinal and Peritoneal Tumors

This research study aims to evaluate the safety and determine the optimal dose of a new experimental drug, vvDD-hIL2 (vaccinia virus double-deleted human interleukin 2), in patients with advanced abdominal cancer. The study will involve three dose levels, with three to six patients enrolled at each level. vvDD-hIL2 is a genetically modified vaccinia virus, derived from the virus previously used for smallpox vaccination. The modification is intended to target and destroy tumors while minimizing harm to healthy tissues by stimulating the body's immune response. Participants will receive an injection of vvDD-hIL2 directly into their abdominal tumors at AHN West Penn. The study team will monitor for side effects and assess tumor response to the treatment. Active participation will last up to two months, involving seven clinic visits and approximately four lab visits at AHN West Penn Hospital. Visits will include standard of care procedures as well as study-specific tests and exams. Most visits will last one to two hours, with some extending to two to three hours. The drug administration day will require a twelve-hour visit. Effectiveness and side effects will be evaluated through blood draws, oral swabs, urinalysis and tissue biopsies. Tissue samples will be used for genomic analysis and stored for potential future research. Data collected may also be used for future research purposes. Previous human trials of vvDD-hIL2 have reported side effects such as pain, rash or inflammation at the injection site, low-grade fevers, flu-like symptoms, and fatigue. There is a rare risk of rash transmission to close contacts with skin openings, and information on limiting contact and managing rash development will be provided.

EPA for Metastasis Trial 2

A significant proportion of patients who undergo liver surgery to remove bowel cancer that has spread to the liver (metastases) develop disease recurrence and die from the disease. A previous small study (the EMT study) suggested a possible survival benefit in patients who took the naturally-occurring omega-3 fatty acid EPA (a fish oil supplement) before liver surgery. The EMT2 study is a larger study which will recruit 448 men and women with liver metastases from bowel cancer. Trial participants will receive either Icosapent Ethyl (pure EPA derived from fish oil) or placebo (dummy capsules). EMT2 will investigate whether patients who take this supplement before liver surgery and for up to four years after surgery, remain free of recurrence for longer than those who take placebo (dummy capsules)

Cryoablation Combined with Sintilimab Plus Lenvatinib in Previously Treated Unresectable Liver Metastasis from Solid Tumors

The objective of this study is to evaluate the efficacy and safety of cryoablation combined with Sintilimab plus lenvatinib for patients with unresectable liver metastasis, who had progressed after, or were refractory to first- or later-line therapy.

Primary Percutaneous Stenting Above the Ampulla Versus Endoscopic Drainage for Unresectable Malignant Hilar Biliary Obstruction

The goal of this clinical randomized controlled trial is to perform primary percutaneous stenting (PPS) in patients with malignant hilar biliary obstruction (MHBO). The main question it aims to answer is: To compare the efficacy of PPS above the ampulla to standard endoscopic biliary drainage (EBD) in patients with a MHBO who are ineligible for surgical resection. Researchers will compare PPS with EBD to see if major complications within 90 days after randomisation occur. Participants will undergo either primary percutaneous stenting or endoscopic biliary drainage, depending on randomization.

The Role and Safety of Radiofrequency Ablation in Recurrent Liver Metastasis of Colorectal Cancer

The goal of this clinical trial is to learn if radiofrequency ablation works to treat recurrent colorectal cancer liver metastases after surgery in adults. It will also learn about the safety of radiofrequency ablation. The main questions it aims to answer are: Is radiofrequency ablation safe and effective in the treatment of recurrent colorectal cancer liver metastases? What medical problems do participants have when treating with radiofrequency ablation? Does radiofrequency ablation enable patients with recurrent colorectal cancer liver metastases to live longer? Researchers will compare systemic therapy combined with radiofrequency ablation to systemic therapy to see if radiofrequency ablation works to treat liver metastases better. Participants will: Receive systemic treatment for colorectal cancer liver metastases. Undergo (or not) radiofrequency ablation for colorectal cancer liver metastases. Visit the hospital once every 3 months for checkups and tests.

Liver Transplantation in Patients With Unresectable Colorectal Liver Metastases Treated by Chemotherapy

This is a multicentric randomized parallel group open trial comparing 5-year survival of chemotherapy followed by LT (Group LT+C) versus chemotherapy alone (Group C) in patients with confirmed unresectable liver-only metastases, well controlled by chemotherapy (no progression) and extensively explored by modern imaging techniques. The primary objective of the trial is to validate in a large multicentric cohort of selected patients the possibility to obtain at least 50% 5-years survival with LT combined to chemotherapy compared to around 10% with chemotherapy alone.

Liver Transplantation and Colorectal Cancer

Colorectal liver metastases (CLM) are currently considered an absolute contraindication for liver transplantation (Lt) although Lt for other primary and secondary liver malignancies show excellent outcome in selected patients. Before 1995, several Lts for CLM were performed, but the outcome was poor (18% 5-year survival) and Lt for CLM was stopped. Since then, several advances have been achieved and survival following Lt has improved by almost 30%. Thus, a 5-year survival of about 50% following Lt for CLM could be anticipated. The investigators have previously included 21 patients in a pilot study. All patients had advanced CLM at the time of Lt. Long term overall survival (OS) exceeds by far previously reported outcome for this patient group and is comparable or better than survival following repeat Lt for non-malignant diagnoses. Development of robust selection criteria may further improve the results. The investigators will conduct a randomized controlled trial to explore whether liver transplantation in selected patients with liver metastases from CRC can obtain significant life extension and better health related quality of life compared to patients receiving surgical resection. The investigators will also explore if patient selection according to nomo-grams for outcome of colorectal cancer can define a subgroup of patients with a 5 year survival of at least 50% or even cure from the disease.

A Combination Therapy Including Anti-PD-1 Immunotherapy in MSS Rectal Cancer With Resectable Distal Metastasis

Although patients with locally advanced rectal cancer and resectable liver/pulmonary metastasis could benefit from surgery resection, these patients still have a poorer prognosis compared to those without distal metastasis. Based on previous studies, there is no confirmation of whether these patients could benefit from preoperative immunotherapy combined with conventional chemoradiotherapy. This study proposes a combination therapy, preoperative short-course radiotherapy followed by neoadjuvant chemotherapy and anti-PD-1 immunotherapy, for microsatellite-stable patients with locally advanced rectal cancer and resectable liver/pulmonary metastasis, to assess its impact on tumor retreat, decline of postoperative metastasis and recurrence, and the disease-free survival and overall survival of patients. Besides, this study will provide high-level medical evidence for future clinical treatment of patients with advanced rectal cancer.