Clinical Research Directory

SAMe in Prevention of Oxaliplatin-associated Liver Injury

This is an open-label, phase II study that may provide evidence that taking S-adenosylmethionine (SAMe) supplementation prevents oxaliplatin, a type of chemotherapy drug, associated liver toxicity in patients with resectable colorectal liver metastases. Resectable means that it is able to removed with surgery. Patients will take two SAMe tablets in the morning and one tablet in the evening for 3-6 months (about 6-8 cycles of chemotherapy) in addition to oxaliplatin based chemotherapy followed by surgical removal of the colorectal liver metastases.

Biopsy After Radioembolization to Identify Changes in Tumor Cells From the Radiation

The purpose of this study is to study the way radioembolization works by collecting biopsy samples of participants' tumors after the procedure. This research may improve the way that radioembolization is performed, which could help people whose cancer has spread to the liver. The research may also provide information about how tumors respond to radioembolization.

Oncolytic Virus (H101) + SBRT + Chemotherapy + Targeted Therapy + Immunotherapy for Unresectable CRLM

This prospective study aims to investigate the efficacy and safety of peritumoral injection of the oncolytic virus H101 in combination with stereotactic body radiotherapy (SBRT), PD-1 monoclonal antibody, chemotherapy, and targeted therapy for the treatment of patients with unresectable, microsatellite stable/mismatch repair proficient (MSS/pMMR) colorectal adenocarcinoma liver metastases. The ultimate goal is to provide high-level evidence-based medical support for this combined modality approach.

Targeted Treatment Plus Tislelizumab and HAIC for Advanced CRCLM Failed From Standard Systemic Treatment

Hepatic arterial infuison chemothearpy (HAIC), targeted therapy, and programmed death-1 (PD-1) inhibitors have been demonstrated to be effective for colorectal cancer liver metastasis (CRCLM). Thus, the investigators will conduct a prospective trial to explore the efficacy and safety of targeted treatment based on ctDNA genotyping combined with tislelizumab and HAIC as salvage treatment for advanced CRCLM failed from standard systemic treatment, aiming to provide individualized optimized regimen for microsatellite stable (MSS) CRCLM in salvage treatment.

Selective Internal Radiation Therapy With 90Y Resin Micropheres for Refractory Colorectal Cancer Liver Metastases

Observational, feasibility study investigating biological aspects in patients with liver metastasis from colorectal cancer undergoing treatment with SIRT, by translational analysis of biological samples.

Precision Medicine for Liver Tumours With Quantitative Magnetic Resonance Imaging and Whole Genome Sequencing

This will be a prospective, observational, cohort study to determine the impact of integrated diagnostics using quantitative magnetic resonance imaging, whole genome sequencing and digital pathology on intended patient management for liver cancer patients referred for liver resection. Participants with primary or secondary liver cancer will be recruited from Hampshire Hospitals NHS Foundation Trust in Basingstoke or Oxford University Hospitals NHSFoundation Trust in Oxford. The incidence of treatable liver tumours is on the rise globally, driven by obesity, viral hepatitis and metastases from colorectal cancers. Survival rates can be improved with optimised allocation of treatment options including surgical resection, radiofrequency ablation, embolisation, chemotherapy and targeted molecular therapies (including immunotherapy). The key motivation of this study is to help patients access the most suitable treatment combinations, based on integrating clinical, radiological and genomic data. A similar integrated approach, integrating radiology and pathology, has been shown to improve outcomes in breast cancer care. Detailed pathologic analysis of the surgical specimen from breast carcinoma biopsy provides valuable feedback to the radiologist, establishes the completeness of surgical intervention, and generates predictive information for therapeutic decisions. Whole genome sequencing (WGS) has discovered cancer driver mutations and the complex molecular profile of liver cancer. In many metastatic solid tumours, WGS has been used to identify a significant patient population (31%) who present with a biomarker that predicts sensitivity to a drug and lacked any known resistance biomarkers for the same drug. Identifying which patients possess druggable mutations will allow clinicians to make the optimal treatment decisions. The next challenge is integrating WGS into scalable clinical practice

Chemoembolization (Lifepearls-Irinotecan) in Patients With Colorectal Cancer and Metastatic Disease

Non-commercial, prospective, randomized, multicenter, national, phase II, open-label comparative clinical trial. The patients will be randomized in a 1: 1 ratio in two arms: Control arm. Systemic chemotherapy with FOLFOX6m + monoclonal Ab Experimental arm. Systemic chemotherapy with FOLFOX6m + monoclonal Ab + Intra-arterial liver chemotherapy with LIFEPEARLS-IRINOTECAN (catheterization and infusion of 100 +/- 50 micron microspheres loaded with 100 mg of irinotecan in both liver lobes) cycles 2 and 4. The main objective is to evaluate the radiological objective response rate according to the RECIST version 1.1 criteria at 6 months. Secondary objectives include: Evaluate overall survival, progression-free survival (PFS), safety profile, hepatic PFS, R0 liver surgery rate.

LDLT in Non Resectable Colo-rectal Cancer Liver Metastasis

This study is an interventional open label prospective study that aims to assess both overall and disease-free survival of patients treated with LDLT, partial or whole graft LT from deceased donors for unresectable CRLM. Secondary outcomes are graft survival and donor outcomes in terms of safety and quality of life. Donor selection is performed according to the currently used Institutional and National standards and protocols.

Prospective Cohort Study on Thermal Ablation of Malignant Liver Tumors

The endpoint of this study is to develop and validate algorithms, using artificial intelligence and machine learning, to optimize patient selection, treatment planning, treatment evaluation and outcome prediction in patients undergoing thermal ablation of a malignant liver tumor. The long-term objective is to establish thermal ablation as the treatment of choice for the vast majority of patients with a primary or secondary liver tumor by development of an accessible workflow that can be widely implemented in different centers performing thermal ablation. Over a time span of at least four years, data will be collected prospectively, encompassing patient information, tumor characteristics, and treatment details. Additionally, pre-, intra-, and post-procedural imaging will be systematically gathered.

Electrochemotherapy (ECT) in Patients With Primary Visceral Tumors and/or Secondary Visceral Localizations, of Any Histotype

This is an monocenter, single arm, clinical investigation that evaluate the impact of the method on the objective response rate (ORR) of visceral lesions undergoing electrochemotherapy. Electrochemotherapy is a well-defined method for the treatment of cutaneous and subcutaneous metastases of different tumor histotypes. Although still limited, the various experiences in the treatment of visceral localizations, particularly in liver metastases from colorectal cancer are promising and show that electrochemotherapy is a safe treatment, even in the case of lesions near large vessels or nerves. The investigators therefore propose a clinical investigation with a Medical Device according to EU Regulation 745/2017, using electrochemotherapy (Cliniporator) with bleomycin for the treatment of visceral, primary or secondary, unresectable localizations, with percutaneous or intraoperative technique (laparoscopic or laparotomy), as needed.

Simultaneous vs. Staged Resection of Colorectal Cancer With Synchronous Liver Metastases

The SYLMET Trial is a randomized trial to compare simultaneous and two-staged resection of primary colorectal and synchronous liver metastases. This is an investigator-initiated, multicentre, randomized controlled trial to assess complications (primary endpoint), survival, cost-effectiveness, and quality of life (secondary endpoints).This trial will include patients with resectable primary tumour in the colon or upper rectum with less than five liver metastases that is possible to treat with surgical resection and/or ablation (RFA/MWA) at time of evaluation.

On-treatment Biomarkers in Metastatic Colorectal Cancer for Life

By virtue of an increased strategic use of cytotoxic and biological agents, and more options for locoregional treatment, the survival of patients with metastatic colorectal cancer (mCRC) has improved considerably in the past decades. The personalized approach to systemic treatment is further aided by the use of complementary molecular biomarkers. However, the evolutionary dynamics of mCRC, a disease harnessed by multiple adaptive genetic alterations towards its final stages, poses a particular challenge to single-sample biomarker analyses and standardized linear treatment protocols. The aim of the On-treatment biomarkers in metastatic ColorectAL cancer for Life (On-CALL) study is to generate further knowledge on the evolutionary progression of mCRC during treatment, and to elucidate the mechanisms underlying the therapeutic failure still seen in a substantial number of patients. The On-CALL study is a prospective, single-arm observational study. All patients diagnosed with synchronous mCRC treated with curative intent at Skåne University Hospital will be invited to participate. Clinical and histopathological data will be compiled at study entry. An individual tissue microarray block with samples from resected primary tumours and metastases representing the full extent of the tumour spread will be constructed for each patient. Blood samples will be drawn for biomarker analyses at multiple time points prior to, during and after systemic treatment. DNA sequencing of tumour tissue and circulating tumour DNA (ctDNA) will be performed to define the spatial clonal landscape in primary tumours and metastases, as well as over time.

Gadoxetate Abbreviated MRI in Metastatic Colorectal Cancer

After a patient is diagnosed with colon cancer, they receive a CT of the chest, abdomen, and pelvis to see if the cancer has spread (metastasized) to other parts of the body. A common site for the cancer to spread to is the liver. If an abnormality is seen in the liver on CT, sometimes an MRI of the liver is required to determine a) whether it is cancer or not and b) whether there are small tumours in the liver that were not visible on CT. During the MRI, the patient is injected with intravenous (IV) contrast. This makes liver lesions more conspicuous and also helps determine if they are cancerous or not. The most commonly used IV contrast agent is called Gadovist. However, there is another IV contrast agent called Primovist that is better at detecting liver metastases from colon cancer than Gadovist. This is very important information for surgeons, because if they considering cutting out (resecting) the liver tumours, they want to make sure they get them all. Unfortunately, Primovist is used sparingly in Canadian hospitals because it is more expensive than Gadovist and the MRI takes longer. Some early small studies have suggested that it may be possible to shorten the Primovist MRI significantly (e.g. from 60 minutes to 15 minutes), making it economically feasible to offer Primovist to more patients. However, there have not been any large studies performed to confirm these findings. The purpose of this study is to compare the accuracy of colon cancer liver metastasis detection between a regular, full-length Primovist MRI versus a shortened Primovist MRI protocol. The economic impact will also be assessed.

Dose Finding, Efficacy and Immunological Response of IP-001 Following MWA or IRE for CRLM

The primary objectives of this phase I/II, prospective clinical trial, are to assess the optimal dose, efficacy, safety and immunological effect of ablation and intra-tumoral injection of a novel immuno-adjuvant (IP-001) for colorectal liver metastases (CRLM). The study consists of three parts, devided into two phases. Phase 1 is a dose-escalation study according to a classic '3+3' design, to identify the dose level at which IP-001 exhibits an acceptable level of toxicity following microwave ablation (MWA) of CRLM in refractory metastatic colorectal cancer (CRC) patients. Phase 2, part 1 and part 2 are performed simultaneously. In phase 2 part 1, a single arm study assesses the efficacy of IP-001 following MWA for CRLM for curative intent. In phase 2 part 2, a randomized, two-armed study assesses the efficacy and immunomodulation of IP-001 following two ablative modalities: arm A (MWA) and arm C (irreversible electroporation (IRE)) for CRLM in refractory metastatic CRC patients.

SBRT of Metastases Following Neo-adjuvant Treatment for Colorectal Cancer With Synchronous Liver Metastases

The purpose of this study is to prospectively evaluate the feasibility of SBRT for the management of synchronous oligo metastatic liver metastases from colorectal cancers.

Detecting Colorectal Cancer With Liver Metastatic Lesions Using Novel Precise Imaging Tools

This study will demonstrate the diagnostic utility of PSMA PET among patients with CRC with liver metastasis.

TANGO-LIVER Three Arm Nuclear Growth Observation in Liver Surgery

Liver resection is the treatment of choice in patients with malignant liver lesions. Unfortunately, the surgery is not always an option, as in same patients the future remnant liver (FRL) is too small to supply all the functions. Therefore, some additional methods have been proposed to increase the size of the FRL. The aim of this study is to compare the efficacy and safety of three methods of increasing the future remnant liver - Portal Vein Embolization (PVE) - embolization of one of the portal branches; Liver Vein Deprivation (LVD) - embolization both of the portal branch as well as the hepatic vein; and partial ALPPS (Associating Liver Partition and Portal vein Ligation for Staged hepatectomy) - ligation of portal vein branch with partial liver transection. The efficacy of those three methods will be assessed both by analyzing the volumetric increase (by computer tomography scans) and by functional increase (by 99mTc-mebrofenin scintigraphy). Functional assessment of the liver hypertrophy seems to be of crucial importance, as some of the previous studies suggest that there might be a significant discrepancy in the increase of size comparing to the increase of function. This is a prospective, interventional randomized study. The study group (154 patients) will consist of patients being considered as candidates for major hepatic resection, after inducing hypertrophy of the future remnant liver. The primary study hypothesis is greater efficacy of ALPPS in preparing patients for large hepatic resection by inducing hypertrophy of the future remnant liver, as compared both to PVE and LVD. In case of unsuccessful induction of hypertrophy by the embolization techniques, patients may be qualified to rescue ALPPS procedure. Primary end-point: Percentage of patients with successful resection (patients, who gained sufficient increase of the FRL to proceed to the liver resection) with no post-surgical 90-day mortality. Secondary end-points: 1. the rate and degree of volume increase in different groups 2. the rate and degree of functional increase in different groups 3. CCI index and complication rate \>=3 degree according to the Clavien-Dindo classification after the first stage of treatment 4. CCI index and complication rate \>=3 degree according to the Clavien-Dindo classification after the second stage of treatment 5. overall duration of hospital stay Patient will be randomly assigned to the three study groups. All patients will undergo an abdominal contrast enhanced computed tomography and 99mTc-mebrofenin scintigraphy prior to the first stage of treatment. During the first stage of treatment, patients will undergo, according to their group: 1. Embolization of portal vein branch (PVE, portal vein embolization) 2. Embolization of both portal vein branch and hepatic vein (LVD, liver venous deprivation) 3. Partial ALPPS (Associating Liver Partition and Portal vein Ligation for Staged hepatectomy) - ligation of portal vein branch with partial liver transection, preferentially by laparoscopic technique Computed tomography scans and scintigraphy will be repeated at day 7, 14 and 21 after the first stage of treatment. The second stage of treatment, the liver resection, will be performed after achievement of sufficient mebrofenin clearance rate (\>=2,69%/min/m2). In case of failure to reach the desired clearance rate, the measurements will be continued every 7 days up to day 42. In case of uncertainty and discrepancy between the volumetric assessment in the computed tomography scan and the mebrofenin scintigraphy, it will be allowed to proceed to stage two (partial hepatectomy) after joint consultation of at least 3 hepatobiliary surgeons, 1 radiologist and 1 nuclear medicine specialist. Routine blood tests will be performed according to the standard procedure in the Department, depending on the patient clinical status. An additional blood sample will be collected from patients (after receiving and additional informed consent from the patient) and will be stored in the biobank. All patients will be monitored for surgical and 90-day complications. The volume increase after first stage of treatment, the functional increase after first stage of treatment, percentage of patients successfully proceeding to the second stage of treatment and complication rate will be calculated. The percentage of patients with complications \>= 3 degree in Clavien-Dindo classification and CCI index for each patient will be calculated. Furthermore, the blood test results will be assessed to search for associations with patients' outcomes. Any possible differences in terms of baseline patients characteristics between groups will be addressed. Statistical analysis will be performed using U Mann-Whitney test, exact Fisher's test, logistic regression, general linear models, Kaplan-Meier method and log-rank test. All three groups will be assessed in terms of occurrence of primary and secondary end-points.

GUIDE.MRD-01-CRC: Clinical Validation and Benchmarking of Top Performing CtDNA Diagnostics - Colorectal Cancer

Improving personalized cancer treatments and finding the best strategies to treat each patient relies on using new diagnostic technologies. Currently, for colorectal cancer, the methods used to decide who gets additional post-surgery treatment are suboptimal. Some patients get too much treatment, while others do not get enough. There is a new way to explore if there is any cancer left in a patient's body using circulating tumor DNA (ctDNA) detected in blood samples. This can help decide who needs more treatment after surgery. Even though many tests have been developed, it has yet to be determined which test performs best at relevant time points. The GUIDE.MRD consortium is a group of experts, including scientists, technology, and pharmaceutical companies. The consortium is working on creating a reliable standard for the ctDNA tests, validating their clinical utility, and collecting data to help decide on the best treatment for each patient. GUIDE.MRD-01-CRC is a part of the GUIDE.MRD project.

Phase 1b Study to Evaluate ATP128, VSV-GP128 and BI 754091, in Patients With Stage IV Colorectal Cancer

This is a multi-center, non-randomised Phase 1b study to evaluate the safety and tolerability of ATP128 alone or in combination with BI 754091 and of heterologous prime-boost ATP128 + VSV-GP128 in combination with BI 754091. ATP128 is a self-adjuvanted chimeric recombinant protein vaccine being developed in combination with programmed cell death 1 (PD-1) blockade for the treatment of microsatellite stable (MSS) patients not responding to PD-1 blockade. The PD-1 inhibitor being tested with ATP128 is the BI 754091 (Ezabenlimab) compound which belongs to the human immunoglobulin G4 (IgG4) subclass of antibodies. VSV-GP is a recombinant chimeric vesicular stomatitis virus (VSV, Indiana strain Rhabdoviridae) which carries the envelope glycoprotein (GP) of the visceral non neurotropic WE-HPI strain of the Lymphocytic choriomeningitis virus (LCMV, Arenaviridae) instead of the native VSV glycoprotein (G) and is developed as integral part of the prime-boost regimen together with ATP128. The Sponsor plans to enrol 96 patients with histologically or cytologically confirmed stage IV colorectal cancer coming form three different patient populations: * Cohort 1a: 6 patients with stage IV colorectal cancer (CRC) having failed standard of care (SoC) therapies * Cohorts 1b, 2a, 2c: 30 patients with stage IV microsatellite stable/mismatch repair-proficient (MSS/MMRp) CRC being in stable disease (SD) or partial response (PR) after first line of SoC (4-6 months duration at minimum) * Cohorts 2b, 4b: 30 patients with stage IV MSS/MMRp liver-limited disease Patients eligible for this study will be enrolled in one of the 8 cohorts depending on their disease: * Patients in Cohort 1a will receive ATP128 as single agent * Patients in Cohorts 1b, 2a, 2b, 2c will receive ATP128 in combination with BI 754091 * Patients in Cohorts 3, 4a, 4b will receive ATP128 and VSV-GP128 in combination with BI 754091

Improving Survival of COlorectal LIver Metastases by RFA-mediated Immunostimulation

To examine radio frequency ablation as a treatment supplement to stimulate immunogenicity and improve survival for patients undergoing curative-intent surgery for colorectal liver metastases.

Application of High-dose Insulin Therapy to Improve Liver Function and Regeneration

The primary objective of this interventional study is determine if the future liver remnant can be optimized by improving liver function pre-operatively in patients who are scheduled for major hepatectomy. The main questions it aims to answer are: 1. Does high-dose insulin therapy improve liver function in the pre-operative setting? 2. What is the effect of high-dose insulin therapy on liver function and liver regeneration after a liver venous deprivation (LVD) procedure? 3. What is the relationship between volume hypertrophy and function in the regenerating liver? Participants will receive a 6-hour infusion of insulin and dextrose to maintain a hyperinsulinemic-normoglycemic state in the weeks prior to planned liver surgery to assess its effect on liver function measured by 99m-Tc-Mebrofenin hepatobiliary scintigraphy.

COLDFIRE-III Trial: Efficacy of Irreversible Electroporation and Stereotactic Body Radiotherapy for Perivascular and Peribiliary Colorectal Liver Metastases

The primary objective of this phase IIb/III, prospective, randomized clinical trial is to compare the efficacy of irreversible electroporation (IRE) with stereotactic body radiotherapy (SBRT) in patients with perivascular or peribiliary colorectal liver metastases (CRLM), that are not amenable for surgical resection or thermal ablation. Efficacy is assessed in terms of local control at 2 years.

Irreversible Electroporation (NanoKnife ®) and Immunotherapy for the Treatment of Stage IV Colorectal Cancer

The goal of this pilot clinical trial is to learn about the combination of immune boosting drugs and irreversible electroporation (IRE) in patients with colon cancer that has spread to the liver (metastasis). The main questions it aims to answer are: 1. to document the rate of complications associated with combining IRE with immune boosting drugs. 2. After one liver metastasis is treated with IRE and immune boosting drugs, what is the change in the size of the non-IRE-treated liver metastases? 3. What is the immune response (measured in a blood sample) when IRE is combined with one or two types of immune boosting drugs?

Fluorescence-guided Resection Of Colorectal Liver Metastases Using SGM-101 and Indocyanine GREEN

This will be the first trial testing the feasibility of working simultaneously with the two fluorescent dyes ICG and SGM-101 in 10 patients with colorectal metastases.