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RECRUITING

NCT04622423

Advanced Therapies for Liver Metastases

Sponsor: IRCCS San Raffaele

View on ClinicalTrials.gov

Summary

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.

Official title: Advanced Immune Gene and Cell Therapies for Liver Metastases

Key Details

Gender

All

Age Range

18 Years - Any

Study Type

OBSERVATIONAL

Enrollment

625

Start Date

2019-11-06

Completion Date

2030-06-30

Last Updated

2026-04-06

Healthy Volunteers

Yes

Conditions

Pancreatic Ductal Adenocarcinoma (PDAC)Colorectal Cancer (CRC)Liver Metastasis IPMN, Pancreatic

Inclusion and exclusion criteria - CRC patients Inclusion criteria: 1. Patients with histologically or cytologically confirmed diagnosis of CRC metastatic to the liver (stage IV disease, AJCC) 2. Patients with indication to surgical resection and/or chemotherapy treatment 3. Age ≥18 4. ECOG PS 0-1 at enrollment 5. Written informed consent 6. Patients will be treated in IRCCS San Raffaele Exclusion criteria: 1. Pregnancy or lactation 2. Inability to provide a written informed consent 3. Extraepatic disease with the exception of selected cases in which the coexistence of extrahepatic disease does not constitute an exclusion criterion for hepatic resective surgery (for example in patients with extraepatic lesions in remission or in any case stabilized by chemotherapy) 4. Severe comorbidities (e.g. cardiac diseases, history of psychiatric disabilities, HIV, autoimmune disorders) 5. Concurrent or previous other malignancy within 5 years of study entry, except cured basal or squamous cell skin cancer, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in-situ of the cervix, or other noninvasive or indolent malignancy 6. Other conditions (medical or psychiatric) that in the judgment of Investigators would make the patient an inappropriate candidate for the study Inclusion and exclusion criteria - PDAC patients Inclusion criteria: 1. Patients with clinical/radiological diagnosis/suspicious of pancreatic adenocarcinoma metastatic to the liver, with subsequent cytological/histological confirmation (stage IV disease, AJCC) 2. Age ≥18 3. Karnofsky performance status ≥50 4. Metastatic pancreatic adenocarcinoma patients with histological specimens from whole liver metastasis biopsy or core liver biopsy collected at IRCCS San Raffaele and stored in the institutional biobank Centro Risorse Biologiche (CRB-OSR) 5. Written Informed consent 6. Patients with clinical/radiological diagnosis of not metastatic primary PDAC that will undergo pancreatic resection at IRCCS San Raffaele Exclusion criteria: 1. Severe comorbidities (e.g., cardiac diseases, history of psychiatric disabilities) representing an absolute contraindication for whole or core liver metastasis biopsy 2. Pregnancy or lactation 3. Inability to provide a written informed consent 4. Metastatic pancreatic adenocarcinoma patients enrolled in other research trials entailing the analysis of the liver metastasis histological sample

Locations (1)

IRCCS San Raffaele

Milan, Milan, Italy