Saint-petersburg, Russian Federation

The Adjunctive Effect of a Titanium Brush in the Non-Surgical Treatment of Peri-Implantitis

Phase 1/2 Study of IMC-R117C in Selected Advanced Cancers

Retrospective Analysis of the Experience With Larotrectinib in Patients With Solid Neoplasms With NTRK Fusion in Spain (SPAINTRK)

1. Study title Retrospective analysis of the experience with Larotrectinib in patients with solid neoplasms with NTRK fusion in Spain (SPAINTRK) 2. .RATIONALE AND OBJECTIVES SPAINTRK aims to be the first trial in Spain to systematically collect data on outcomes of Spanish patients with solid neoplasms treated with Larotrectinib through the compassionate drug use program, during the time elapsed between the indication approval and the drug commercialization. This will contribute to selection of the best treatment for cancer patients with NTRK fusions, such as Trk inhibitors like Larotrectinib. Since the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) approved the use of Trk inhibitors, like Larotrectinib, there is a new and effective option of treatment for patients with NTRK fusions in solid neoplasms. This observational retrospective study will allow to analyze data of patients treated with Larotrectinib across the country and increase the knowledge on response to rare and different cancers 2.1 Main Objective Description of the effectiveness of Larotrectinib treatment in tumors with NTRK fusion in Spanish patients as a clinical series. 2.2. Secondary Objectives - Describe treatment duration, including dose reductions and interruptions occurred along the treatment with Larotrebtinib, as well as to study the reasons behind those decisions. - Study the effectiveness of Larotrebtinib and previous lines of therapy. Identified the line of treatment at which molecular testing for NTRK was performed. - Exploration of clinical and/or histological variables related to the effectiveness and tolerability of Larotrectinib treatment. 3. RESEARCH METHODS 3.1. Study design This is an observational retrospective study including thyroid cancer patients with solid neoplasms with NTRK fusions. The study will use secondary data retrieved from medical records from each patient. The medical records include all the clinical variables defined in order to perform the analysis and it is not necessary to access additional sources. The assignment of a patient to a specific therapeutic strategy has been already decided in advance by the usual clinical practice of medicine; the decision to prescribe a specific treatment was clearly dissociated from the decision to include a patient in the study. No intervention will be applied to patients, either diagnostic or follow-up, other than the usual clinical practice. Epidemiological methods will be used to analyze the data collected. 3.2. Setting and study population In total, 19 patients diagnosed with solid neoplasms that have been confirmed to bear NTRK fusions in their tumors will be included in the study. It is known that these patients have received the treatment with Larotrectinib in 14 centers in Spain, prior to treatment reimbursement in Spain. 3.3. Inclusion Criteria Infant and adult patients (all ages). Patients with confirmed diagnosis of solid neoplasms. Patients must have detected NTRK fusions by the following diagnostic methods NGS, fluorescence in situ hybridization (FISH) and/or Immunohistochemistry (IHC). Patients must be treated with Larotrectinib under the compassionate use program (before the commercialization) in order to be included in the study. Data should be available in order to evaluate effectiveness and consequent follow up. 3.4. Exclusion Criteria Patients with solid neoplasms treated with Larotrectinib in clinical trials or other settings different from clinical practice. Patients that initiated treatment with Larotrectinib after the obtention of prize-reimbursement and commercialization. 3.5. Study Size The sample size calculation is based on the actual number of patients known to be treated in Spain with Larotrectinib. At the moment 19 patients from 14 different healthcare centers have been localized that were treated in the Spanish territory with Larotrectinib. We expect to include and collect data from all of them. fusions, such as Trk inhibitors like Larotrectinib. Since the Food and Drug
 Administration (FDA) and the European Medicines Agency (EMA) approved the use of Trk
 inhibitors, like Larotrectinib, there is a new and effective option of treatment for
 patients with NTRK fusions in solid neoplasms. This observational retrospective
 study will allow to analyze data of patients treated with Larotrectinib across the
 country and increase the knowledge on response to rare and different cancers 2.1
 Main Objective Description of the effectiveness of Larotrectinib treatment in tumors
 with NTRK fusion in Spanish patients as a clinical series.
 
 2.2. Secondary Objectives
 
 - Describe treatment duration, including dose reductions and interruptions
 occurred along the treatment with Larotrebtinib, as well as to study the
 reasons behind those decisions.
 
 - Study the effectiveness of Larotrebtinib and previous lines of therapy.
 Identified the line of treatment at which molecular testing for NTRK was
 performed.
 
 - Exploration of clinical and/or histological variables related to the
 effectiveness and tolerability of Larotrectinib treatment.
 
 3. RESEARCH METHODS 3.1. Study design This is an observational retrospective study
 including thyroid cancer patients with solid neoplasms with NTRK fusions.
 
 The study will use secondary data retrieved from medical records from each patient.
 The medical records include all the clinical variables defined in order to perform
 the analysis and it is not necessary to access additional sources.
 
 The assignment of a patient to a specific therapeutic strategy has been already
 decided in advance by the usual clinical practice of medicine; the decision to
 prescribe a specific treatment was clearly dissociated from the decision to include
 a patient in the study. No intervention will be applied to patients, either
 diagnostic or follow-up, other than the usual clinical practice. Epidemiological
 methods will be used to analyze the data collected.
 
 3.2. Setting and study population In total, 19 patients diagnosed with solid
 neoplasms that have been confirmed to bear NTRK fusions in their tumors will be
 included in the study. It is known that these patients have received the treatment
 with Larotrectinib in 14 centers in Spain, prior to treatment reimbursement in
 Spain.
 
 3.3. Inclusion Criteria Infant and adult patients (all ages). Patients with
 confirmed diagnosis of solid neoplasms. Patients must have detected NTRK fusions by
 the following diagnostic methods NGS, fluorescence in situ hybridization (FISH)
 and/or Immunohistochemistry (IHC).
 
 Patients must be treated with Larotrectinib under the compassionate use program
 (before the commercialization) in order to be included in the study.
 
 Data should be available in order to evaluate effectiveness and consequent follow
 up.
 
 3.4. Exclusion Criteria Patients with solid neoplasms treated with Larotrectinib in
 clinical trials or other settings different from clinical practice.
 
 Patients that initiated treatment with Larotrectinib after the obtention of
 prize-reimbursement and commercialization.
 
 3.5. Study Size The sample size calculation is based on the actual number of
 patients known to be treated in Spain with Larotrectinib. At the moment 19 patients
 from 14 different healthcare centers have been localized that were treated in the
 Spanish territory with Larotrectinib. We expect to include and collect data from all
 of them.
 3.6. Sampling and recruitment method Patients will be consecutively included, in compliance with the previously established inclusion criteria. According to the definition of study population and disease established in this scientific report, patients will be selected from cases diagnosed with solid neoplasms bearing NTRK fusions detected by any of these methods, NGS, FISH and/or IHC, and treated with Larotrectinib. The 19 patients treated with Larotrectinib in the Spanish territory are localized and belong to 14 different sites/healthcare centers. To prevent two or more reporting physicians from logging the same case, a coordinator, who controls the cases included in his or her center, is appointed in health centers with several reporting physicians, and preventive measures are implemented in the tool controlling duplications in variables (such as birth date, gender, center or diagnosis). 3.7. Case Definition A 'case' is defined as any patient, diagnosed, treated, or followed in the different health centers where reporting physicians authorized by the sponsor, who meets the inclusion criteria. A key point is that the patient was diagnosed with solid neoplasms that harbors a NTRK fusion and he/she was receiving treatment with Larotrectinib. Data from patient's treatment should have been recorded and be available at the centers. 3.8. Data Logging Once the patient is compliant with inclusion/exclusion criteria information on the clinical history will be collected to gather the necessary data and to complete the electronic forms of the study designed for this purpose. All data collected during treatment, as well as demographic data, will be provided for the purpose of this study and completed at the electronic Case Report Form (eCRF) to proceed to its analysis. 4. ENDPOINTS AND VARIABLES 4.1. Endpoints 4.1.1. Primary Endpoints Duration of response (DoR): is defined as the time from first confirmed response (complete (CR) or partial (PR) response), according to Objective response rate (ORR) defined below, to the date of the documented progression of the disease (PD) as determined using RECIST V1.1 criteria or death due to any cause, whichever occurs first. Those patients with response and without PD or death event will be censored on the date of their last tumor assessment. Results will be presented as individual cases, not compiled as the patients have different pathologies which may differ in prognosis. 4.1.2. Secondary Effectiveness Endpoints - Objective response rate (ORR): is assessed by the investigator analysis of tumor growth through imaging follow-up (CT scan/MRI), using a method to evaluate it as RECIST V1.1. This will be considered as the number of patients with confirmed complete response (CR) or partial response (PR) as their overall best response throughout the period of treatment with Larotrectinib. Tumor measurements that were assessed locally by the clinician according to RECIST, V1.1, should be recorded and indicate the change in size of tumors as compared with baseline, at the first dose of study treatment. - Progression free survival (PFS): Time from first dosing date to the date of confirmed PD according to RECIST 1.1. Patients alive and free of events at the date of the analysis will be censored at their last known tumor assessment. Patients who start a new treatment line without progression will be censored on the date of first dose of the subsequent anticancer treatment. - Overall survival (OS): defined as the time elapsed from the first dose of study treatment until death from any cause. Patients alive and free of events at the date of the analysis will be censored at their last known contact. Survival will be assessed by recording patients' status at each visit. Results will be presented as individual cases, not compiled as the patients have different pathologies which may differ in prognosis. 4.1.3. Secondary Safety Endpoints -Safety: All safety information will be collected retrospectively according to data available in the chart review. A descriptive analysis of adverse events collected in medical charts will be done taking into account: 1. The frequency of Adverse events (AEs) will be reported per patient by MedDRA System Organ Class (SOC) and Preferred Term (PT); 2. The maximum CTCAE grade will be reported per patient; 3. The causal relationship with the study drug will be assessed locally by the investigator - Larotrectinib interruptions / Delays: number of interruptions and delays of treatment reported per patient (frequency) and reason for dose interruption / delay. - Larotrectinib dose reductions or modifications: Number of reductions or modifications of doses reported per patient (frequency) and reason for dose reduction / modification. - Larotrectinib treatment duration: Time elapsed between first dose and permanent discontinuation of the study treatment. 4.2. Study Variables Investigators will provide information of each of the following variables: Variables for Demography: - Age at enrollment. - Sex (male, female). - Race (white, black, Asian, other) - Height (cm). - Weight (kg). - Body mass index. - Body surface area (BSA) - calculated from the reported height and weight using Mostseller's formula: BSA (m2)= (height (cm) x weight (kg) / 3600) 1/2 - Performance status.will be presented using the Eastern Cooperative Oncology - Group (ECOG) scale. Cancer history: - Primary cancer diagnosis. - Primary tumor type, histology and location - Stage of disease at initial diagnosis(I-IV). - Time since initial diagnosis. - Extent of disease at enrollment (metastatic, locally advanced, sites of disease, presence of at least one measurable lesion). Stage of the disease at inclusion - Time since diagnosis of metastatic or locally advanced disease (years). Prior anticancer treatments: -Prior systemic treatments type, start and end dates. -Number of prior systemic regimens or treatment courses. -Best overall response to the most recent prior systemic regimen or treatment course (CR, PR, stable disease, progressive disease, unknown or inevaluable or not applicable). -Prior radiotherapy. -Prior cancer-related surgery. NTRK fusions: -NTRK fusion gene: NTRK1, NTRK2, NTRK3. -NTRK fusion isoform (i.e ETV6-NTRK3). -Method of detection: NGS, FISH or IHC and dates of the determinations. - Other oncogenic alterations present. Treatment with Larotrectinib: -Dose of Larotrectinib. -Larotrectinib start and end date. Reasons for end of treatment -Data records of dose reductions and/or interruptions and their reason. -Best response and best response date -Progression date. -Frequency of AEs reported per patient by MedDRA System Organ Class (SOC) and Preferred Term (PT); the maximum CTCAE grade will be reported per patient. Causal relationship with the study treatment will be reported for all events. Survival: - Patient status (alive, death, lost to follow-up) - Reasons of death (if applicable) - Subsequent anticancer treatments (type, start and end dates, best response, progression dates)

+AGIL Barcelona: Integrated Care for Community-Dwelling Frail Older Adults

Population aging requires the implementation of sustained integrated strategies and programs to improve intrinsic capacity and delay disability in older adults. The +AGIL Barcelona program exemplifies a pragmatic, multicomponent intervention that effectively improves physical function by integrating health and community resources. This study aims to co-design, adapt, and scale up +AGIL to diverse socioeconomic areas in Barcelona, assessing its effectiveness and evaluating the process of progressive implementation. Methods: Multicenter, pragmatic, Stepped-Wedge Cluster Randomized Trial, performed in three Primary Care Centers in Barcelona (PCCs), involving older adults screened as frail by the Gérontopôle Frailty Screening Tool (total sample size=396, 198 per arm). After a co-design phase to adapt the protocol to each local context, the intervention will be introduced sequentially at each site, according to a randomly determined schedule, until all PCCs are exposed. The intervention, previously piloted in a different PCC, is based on a Comprehensive Geriatric Assessment followed by a 10-week tailored boost multicomponent intervention aligned with the Integrated Care for Older People (ICOPE) framework of the World Health Organization - WHO - (physical exercise being the core element). After three months, continuity of activation is pursued through the integration of community resources (public or private gyms, civic centers etc). The primary outcome will be. The investigators designed a mixed-methods evaluation, measuring physical performance improvement using the Short Physical Performance Battery (SPPB) as the primary quantitative outcome, plus a qualitative assessment of participants' experience and program implementation. Discussion: This study will provide relevant information on the implementation and impact of pragmatic, real-life interventions to improve intrinsic capacity and prevent disability in older adults.

Oral Anticoagulation Versus Left Atrial Appendage Occlusion Added to Direct Oral Anticoagulation in Patients with Stroke Despite Oral

Background: The prevalence of atrial fibrillation and the number of patients experiencing ischemic strokes despite being on oral anticoagulation (OAC) are both increasing. This rise presents a significant challenge due to the absence of clear and uniform treatment recommendations for these patients. To date, there is no formal combination that merges a high anticoagulant efficacy while keeping a low bleeding risk. Transcatheter left atrial appendage occlusion (LAAO) added to OAC might provide a balance between efficacy and safety. Objectives: To evaluate if, in patients with ischemic stroke despite OAC, the combination of LAAO and long-term direct OAC (DOAC) or OAC is associated with a lower incidence of recurrent cardioembolic events at 12 months as compared to the best medical treatment proposed by the neurologist. Methods: A total of 380 patients with ischemic stroke despite OAC will be included. Patients will be randomized 1:1 to the best medical treatment (control) or the combination of LAAO and DOAC or OAC. The study's primary endpoint will be the occurrence of a cardioembolic event (ischemic stroke or arterial peripheral embolism) within the first 12 months after inclusion. Implication: This study is one of the first randomized trials comparing the LAAO+DOAC combination to optimal medical treatment in patients who have had ischemic strokes despite being on OAC. If the results confirm the superiority of LAAO+DOAC, it could lead to a paradigm shift in treatment guidelines for these patients.

A Study of Roginolisib (IOA-244) in Combination With Dostarlimab With or Without Docetaxel in Metastatic Non Small-cell Lung Cancer (NSCLC) Patients

A Phase I/IIa open-label, randomised study of oral roginolisib (IOA-244 [roginolisib hemi-fumarate]) in combination with dostarlimab with or without docetaxel in Advanced Non small-cell lung cancer (NSCLC) patients. This study will enrol approximately 45 male and female patients aged over 18 years with advanced NSLCL who have process on standard of care immune checkpoint therapy and platinum doublet chemotherapy or standard immunotherapy without chemotherapy. The disease must be measurable (i.e., at least 1 measurable lesion) as per RECIST v1.1 by Computerised Tomography (CT) scan or Magnetic Resonance Imaging (MRI).

HYbrid RObotic Surgery MulTiCentric Study

The ROB-Bitrack System is 4-arms on demand open and portable robotic platform indicated to be used during general abdominal laparoscopic surgical procedures. This robot is intended to assist in the accurate control of endoscopic instruments and accessories for endoscopic visualization and manipulation of tissue. The HYROS-MTC-I clinical investigation will be conducted as a multi-center, with a single arm, open-label, and non-randomized design, that will include 50 patients. The study shall refer to effectiveness of ROB-Bitrack System together with its accessories and corresponding ESE/NESE instruments. The planned visits for this clinical investigation are baseline (includes Screening, baseline visit, and Informed consent), procedure, discharge, 14-Days and 30-Days Follow-up visit . The clinical investigation will include adult subjects (between 18 and 90 years old) who have been scheduled for laparoscopic Radical Nephrectomy, Partial Nephrectomy or Radical Prostatectomy. The expected duration of the study is 12 months from the first patient enrolled, including 11 months of enrollment and the follow up of 30 days after surgery. The end of the clinical investigation will occur when the last visit of the last enrolled subject is completed.

Troubled-Desire & Therapeutic Chat for Reduction of CSAM Use (TD-CHAT)

The study will evaluate whether the TCS intervention and Selfhelp modules, independently or combined, effectively reduce CSAM use or risk of CSAM consumption and improve mental well-being among self-referred participants. 1. Objectives 1.1 Primary objectives 1. To compare the effectiveness in reducing CSAM behaviours between the TD only group and the waitlist group four weeks after the baseline assessment. 2. To compare the post-intervention effectiveness in reducing CSAM behaviours of the Selfhelp modules versus TCS alone and Selfhelp modules followed by TCS. 1.2 Secondary objectives 1. To assess the reduction in severity, time and self-rated risk of CSAM consumption among participants in the intervention groups (Selfhelp modules, TCS, or Selfhelp + TCS) compared to the waitlist control group, at post-intervention. 2. To compare the impact of the interventions (Selfhelp modules, TCS, or Selfhelp + TCS) on mental wellbeing, in contrast to the control group, at the end of the intervention period. 3. To evaluate the effect of the interventions (Selfhelp modules, TCS, or Selfhelp + TCS) on total sexual outlet compared with the waitlist control group after the intervention period. 4. To identify any adverse effects associated with the interventions (Selfhelp modules, TCS, or Selfhelp + TCS). 2. Hypotheses 2.1 Primary hypothesis 1. Participants in the Selfhelp-only modules group will show a statistically significantly higher proportion of reduction in CSAM behaviours four weeks after baseline, as compared to participants in the waitlist control group. 2. Participants in the Selfhelp modules followed by TCS group will show a statistically significantly higher reduction of CSAM behaviours compared to participants in the Selfhelp-only and TCS-only groups, post-intervention. 2.2 Secondary hypothesis 1. Participants in the intervention groups (Selfhelp modules, TCS, or Selfhelp + TCS) will show a statistically significant reduction in the severity, time and self-rated risk of CSAM consumption compared to participants in the waitlist control group, four weeks after the initial intervention. Among the intervention groups, it is expected that the Selfhalp + TCS group will show the greatest reduction in CSAM consumption, followed by the TCS group and then the Selfhelp-only group. 2. Participants in the intervention groups (Selfhelp modules, TCS, or Selfhelp + TCS) will show a statistically significant improvement in their mental well-being (measured using the Warwick-Edinburgh Mental Wellbeing scale). compared to participants in the waitlist control group, at post-intervention. Among the intervention groups, the Selfhelp + TCS group is expected to show the greatest improvement, followed by the TCS group, and then the Selfhelp-only group. 3. Participants in the intervention groups (Selfhelp modules, TCS, or Selfhelp + TCS) will show a statistically significant reduction in total sexual outlet (measured using a self-reported measure) compared to participants in the waitlist control group, after the intervention. Among the intervention groups, the Selfhelp + TCS group is expected to show the greatest reduction, followed by the TCS group, and then the Selfhelp-only group. 4. All intervention groups (Selfhelp modules, TCS, or Selfhelp + TCS) will experience adverse effects (psychological and emotional distress) to a similar extent, with no significant differences in the number or type of adverse effects reported. Adverse effects are expected to primarily involve mild to moderate psychological and emotional distress, such as feelings of anxiety or frustration, but are not expected to lead to severe distress or long-term harm. 3.Trial design This is a prospective, randomised, multicentre, open-label, parallel-group, superiority trial designed to compare stratified, pair-matched CSAM users across three intervention groups and one wait-list control group, with an allocation ratio of 1:1:1:1. Following participant agreement to the terms of the study, demographic information, measures for stratified randomization, and baseline outcome data will be collected. Additionally, data collected from the four groups Selfhelp modules, TCS, Selfhelp + TCS, and waitlist) of the TD-CHAT study will be compared with data from a fifth group (waitlist + TCS) sourced from the "Scalable Technology for Online Prevention of Child Sexual Abuse and Child Sexual Abuse Materials" (STOP-CSAM) project.

APACE - Feasibility of Using Accelerometers to Measure Physical Activity in Cancer Patients on Early Phase Clinical Trials

European Registry of Next Generation Imaging in Advanced Prostate Cancer

This registry is intended to collect real-world data on patient demographics, medical history, clinical endpoints, histological tumour characteristics and imaging explorations of the patients with prostate cancer at high risk for harbouring metastatic deposits at the hormone-sensitive stage, who require imaging exploration (conventional, NGI, or their combination) either at the diagnostic workup of a "naïve" patient or at biochemical relapse/progression after local treatment. Stage 1: cross-sectional observation 1. To identify the proportion of patients for whom an imaging work-up with NGI at baseline may result beneficial, according to physician criteria. 2. Assess management prompted by NGI vs. conventional imaging in usual clinical practice. 3. To identify the proportion of patients for whom conventional imaging is considered informative enough for making a clinical decision, according to physician criteria. 4. Stratification of metastatic prostate cancer patients by the number, volume, and location of deposits, according to the different imaging tools employed. 5. Reclassification of HSPC (M0 vs low vs. high volume) based on NGI respect to CI when both imaging modalities are used. Stage 2: longitudinal observation 1. Evaluation of survival outcomes and their relationship with the imaging pathway undertaken (overall and per subgroup of imaging modality). 2. Identification of prognostic factors related to treatment response and disease progression.