Clinical trials

The MAZINGA study is a multicenter, open-label, single-arm Phase IIA clinical trial designed to evaluate the efficacy, safety, and tolerability of zanubrutinib in patients with IgM anti-myelin-associated glycoprotein (anti-MAG) antibody-associated demyelinating polyneuropathy. Anti-MAG neuropathy is a rare immune-mediated disorder frequently associated with IgM monoclonal gammopathies, including monoclonal gammopathy of undetermined significance (MGUS), Waldenström macroglobulinemia, marginal zone lymphoma, chronic lymphocytic leukemia, and other indolent B-cell lymphoproliferative disorders. The primary objective of the study is to determine whether 12 months of treatment with zanubrutinib leads to a clinically meaningful neurological improvement, defined as an improvement of at least one point in at least two validated neurological scales. These include reductions in the Overall Neuropathy Limitations Scale (ONLS), INCAT Disability Score, and INCAT Sensory Sum Score (ISS), along with increases in the Medical Research Council (MRC) sum score and the I-RODS functional score. Secondary objectives include the evaluation of neurophysiological improvement assessed by nerve conduction studies (ENG/EMG), particularly changes in distal motor latency, terminal latency index, and sensory action potential amplitude at 12, 24, and 48 months. Additional secondary endpoints assess hematological efficacy through overall response rate (complete response, very good partial response, or partial response), event-free survival, time to neurological progression, and overall survival. The safety profile of zanubrutinib will be characterized by the incidence, type, and severity of adverse events, serious adverse events, and events of special interest. Eligible participants are adults (≥18 years) with a confirmed diagnosis of anti-MAG IgM-associated demyelinating polyneuropathy, evidence of a relevant IgM monoclonal gammopathy, elevated anti-MAG antibody titers, and measurable neurological disability. Both treatment-naïve and relapsed/refractory patients are eligible. Key exclusion criteria include prior treatment with BTK inhibitors, aggressive lymphomas, significant axonal damage, uncontrolled comorbidities, active infections, pregnancy, or conditions that could interfere with study participation or safety evaluation. The planned sample size is approximately 50 patients recruited from nine Italian centers. Statistical analyses will compare neurological outcomes with historical controls, estimate survival endpoints using Kaplan-Meier methods, and explore associations between clinical outcomes and molecular features. This study aims to provide robust prospective evidence on the role of BTK inhibition in anti-MAG neuropathy and to inform future therapeutic strategies for this rare and disabling condition.

Pancreatic cancer is a severe disease often diagnosed at an advanced stage, when surgery is not possible. New chemotherapy treatments can sometimes shrink the tumor and make surgery an option. This study aims to understand if surgery after such treatments can improve survival and quality of life in selected patients treated at expert centers.

The PARTNER study is an international, prospective, observational study of paediatric patients with very rare tumours.

BACKGROUND: Patients with trivial branch duct intraductal papillary mucinous neoplasm (BD IPMN) which remain s stable over 5 years reportedly do not have an increased risk of developing pancreatic cancer (PC) compared to the general population. In these patients, d iscontinuation of surveillance seems feasible . However, prospective studies to confirm the safety of this approach are lacking. AIM: To assess whether current surveillance policies for stable, trivial BD IPMN can be discontinued safely after 5 years of follow up . METHODS: TRIVIAL is an international prospective multicenter single arm trial exploring discontinuation of surveillance in patients with at least 5 years stable trivial BD IPMN. The trial will include 394 adult patients at least 70 years of age with BD IPMN ≤ 30 millimeter without worrisome features or high risk stigmata during 5 years. The primary endpoint is rate of PC and futile surgery (i.e., surgery for low grade dysplasia IPMN or other non malignant pathology) during 5 year follow up. The predefined target is a rate of 1% and below 3%. STRENGTHS: The burden for patients to participate in this trial is negligible. P atients will only be asked to answer self reported digital surveys once per year during five years . The potential benefits for patients are twofold: the psychological impact of potentially unnecessary surveillance will be spared to patients , whereas the socio economic burden of repeated imaging will be avoided. Moreover, the study will provide data contributing to the development of new, evidence based surveillance strateg ies At the end of follow up patients undergo MRCP to assess disease course (i.e., development of worrisome features, high risk stigmata, PC). LIMITATIONS: The most prominent risk of IPMN is the development of pancreatic cancer However this risk will not be omitted fully by the TRIVIAL trial eligibility criteria as participants still have the same risk as the general population. This requires adequate counselling

The goal of this prospective observational study is to validate pEEG as a monitoring tool for the analgosedation level in mechanically-ventilated critically ill children, receiving or not-receiving NMBAs. The main question aims to answer is to measure the strength of agreement between pEEG score and Comfort Behavioural Scale (CBS) (goal standard). Participants will be monitored with pEEG and CBS evaluated during PICU admission. paralysis holiday) by a specialized PICU nurse and by a critical-care expert physician, blinded to each other.

An increase of intracranial pressure (ICP) is an important cause of secondary brain damage. The gold standard for measuring ICP is represented by invasive positioning of intracranial ICP devices. The most used non-invasive methods (nICP) are obtained through bed-side ultrasound, routinely used in the management of children in Pediatric Intensive Care: arterial Trancranial Doppler (TCD) and ultrasound measurement of the diameter of the optic nerve sheath (ONSD ). In this study it is proposed to compare the measurement of nICP obtained by TCD and ONSD versus the measurement obtained by the invasive monitoring (iICP) already present.

Cholangiocarcinoma (CCA) represents the most common biliary tract malignancy, and the second most common primary hepatic malignancy, accounting for 15% to 20% of primary liver tumours. Perihilar cholangiocarcinoma (pCCA) involves the biliary confluence with or without involvement of the right and left hepatic ducts. Complete resection with negative histologic margins is the only chance of cure and the most robust predictor of long-term survival for patients affected by any type of locally advanced CCA. However, the proximity of perihilar tumors to vital structures makes curative excision technically difficult. Minimally invasive approaches are progressively spreading in liver surgery units worldwide. Significant advantages of minimally invasive liver resections, if compared to open one, have been diffusely shown, such as shorter hospital stay and possibility of complex reconstructive procedures similar to those performed in open surgery. Robot-assisted liver surgery represents a natural consequence of such a minimally invasive evolution. This is a monocentric, single arm, observational, prospective study that aims at analyzing the outcomes of robotic major liver resection and biliary recontruction for perihilar cholangiocarcinoma. Among study outcomes, the primary outcome is evaluation of morbidity; secondary outcomes includes conversion rate, margin status, biliary fistula, liver failure, disease specific survival, overall Survival Data related to patient condition (laboratory tests, etc.), surgery performed, and post-surgical course will be collected. The protocol for this study has been developed in accordance with the European Union Good Clinical Practice guidelines and the Declaration of Helsinki, and it has been approved by the Territorial Ethics Committee of the East-Central Veneto Area (CETAEV).

This study investigates the impact of surgical resection compared to palliative care in patients with oligometastatic pancreatic cancer limited to the liver. Specifically, it examines whether surgery after stable disease or response to chemotherapy can improve survival and quality of life. The international, multicenter randomized trial will recruit 56 patients, assigning them to either surgical resection (including tumor and liver metastases) or ongoing palliative care with chemotherapy. Stratification by performance status, tumor markers, and tumor location will ensure balanced study groups. Outcome assessments, conducted over a minimum two-year follow-up, include clinical evaluations, imaging, and quality-of-life metric

ULTRA-LAP is a prospective study is to investigate the safety, efficacy and feasibility of laparoscopic debulking surgery (LDS) for the treatment of patients with advanced ovarian cancer. The outcomes to measure are: * Safety: the rate of patients experiencing intra- and post-operative early and late morbidities (within the hospitalization and up to 60 days from surgery) * Efficacy: the rate of patients in which the surgical target set pre-operatively (complete resection) is achieved by laparoscopy. * Feasibility: the rate of patients who have their procedure completed by laparoscopy Patients will undergo laparoscopic debulking surgery (LDS) if the surgical target can be met. If it cannot be achieved by laparoscopy the surgeon will convert to laparotomy.