Jīma, Ethiopia

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)

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.

Development of a Predictive Model for Sexually Transmitted Infections in Individuals Using Pre-Exposure Prophylaxis for HIV in Spain

A Study of Sequential Therapy With Daplusiran/Tomligisiran (DAP/TOM) Followed by Bepirovirsen in Participants Living With Chronic Hepatitis B (CHB)

Talazoparib Plus Enzalutamide After Progression to Abiraterone in Metastatic Prostate Cancer: (TEAM PC)

This is a multicenter, open-label, randomized, phase II trial to evaluate the efficacy of the combination of talazoparib plus enzalutamide versus enzalutamide as first line treatment for metastatic castration resistant prostate cancer (mCRPC) in participants whose disease has progressed to abiraterone based treatment for metastatic hormone sensitive prostate cancer (mHSPC). Participants who meet the eligibility criteria will be randomized 1:1 to the experimental arm (enzalutamide and talazoparib) or control arm (enzalutamide) and will receive treatment until disease progression, unacceptable toxicity, death or discontinuation from the study treatment for any other reason. Prostate cancer is the second most common malignancy in men worldwide with an estimated annual global incidence of 1.3 million and over 375,000 deaths. Aggressive variant prostate cancer is a clinically defined subset of metastatic castration resistant prostate cancers (mCRPC) characterized by the absence of response to androgen receptor (AR) targeted agents and neuroendocrine features. The treatments that are currently available are not effective, representing an unmet clinical need. The combination of talazoparib, a potent selective PARP inhibitor (PARPi) and enzalutamide (androgen receptor signaling inhibitor; ARSi) demonstrated in the TALAPRO-2 study improved efficacy in metastatic castration resistant prostate cancer (mCRPC) participants with and without DNA damage response (DDR) gene alterations as first line treatment (1L) compared to enzalutamide alone. Up to 78 participants will be enrolled and randomized 1:1 to the experimental and control arms.Up to 19 participants will be allocated into the experimental arm in Stage 1. An interim analysis will be triggered once each patient on the experimental arm has been followed up for at least 16 weeks (or earlier if response status can be ascertained definitively) to decide whether to proceed to Stage 2 or discontinue the study. If greater than or equal to 6 responses are observed, recruitment will continue to Stage 2, enrolling 20 more participants on each arm; otherwise, the trial will stop. Estimated duration of the study: 36 months. Accrual is expected to be completed in 18 months. Median treatment duration has been estimated in 10 months. After completion of (or discontinuation from) treatment, participants will be followed up for survival until end of study (EoS) that will occur at 18 months after the enrollment of the last patient included in the trial, unless premature termination of the study. It is hypothesized that after progression to abiraterone, the addition of talazoparib to enzalutamide as 1L for mCRPC will result in improved PSA response rate and delayed progression compared to enzalutamide alone.

Development and Validation of a Blood Test for Early Diagnosis of Colorectal Cancer

Utility of ROTEM® for Risk Stratification of Post-Invasive Procedure Hemorrhage in Patients With Cirrhosis (CIR-ROTEM)

Effect of Cryotherapy in the Prevention of Madarosis Produced by Chemotherapy in Breast Cancer Patients

Background: Chemotherapy-induced alopecia (CIA) is one of the most distressing adverse effects for breast cancer patients, particularly when involving eyebrow and eyelash loss (madarosis). While scalp cryotherapy has demonstrated efficacy in reducing CIA, no standardized protocols exist for preventing madarosis. Preliminary studies suggest localized cryotherapy may mitigate this effect but robust evidence is lacking. Objectives: The primary objective is to evaluate the efficacy of supraorbital cryotherapy in preventing anthracycline- or taxane-induced madarosis in breast cancer patients. Secondary objectives include: (1) Quantifying chemotherapy-induced alopecia of eyebrows (madarosis) and eyelashes (milphosis) in control groups, (2) developing a novel alopecia classification scale for eyebrows and eyelashes (currently nonexistent), (3) assessing quality-of-life impact using validated questionnaires "European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-BR23 (EORTC QLQ-BR23)" and, and Eyelash Satisfaction Questionnaire (ESQ). (4) monitoring cryotherapy-related adverse events (e.g., headache, localized pain). Methodology: This non-randomized, quasi-experimental multicenter trial will be conducted at hospitals in Salamanca and Santander. The study population will comprise 120 breast cancer patients receiving anthracycline/taxane-based chemotherapy (sample size may be adjusted based on recruitment). Inclusion criteria: women >18 years old with recent diagnosis and no prior treatments. The intervention group will receive supraorbital cryotherapy using temperature-controlled devices (-4°C to -7°C) applied 15 minutes before chemotherapy infusion and maintained for 20 minutes post-infusion. Outcome Measures: Primary outcomes will be assessed via: - Photogrammetric analysis (TIDOP Research Group) at four timepoints: baseline, mid-treatment, end-of-treatment, and 1-month follow-up. Hair retention will be quantified using automated AI algorithms (DAM-Net). - Patient-reported outcomes using the EORTC QLQ-BR23 and ESQ questionnaires. - Adverse event monitoring through ad hoc surveys. Statistical Analysis: Data will be analyzed using ANOVA and Mann-Whitney tests for intergroup comparisons, Pearson/Spearman correlations for continuous variables, and linear regression to identify predictive factors. Ethics: The study has been approved by the Ethics Committees of Salamanca Health Area (Ref: 2023 09 1427) and Hospital Universitario Marqués de Valdecilla (Cantabria, Spain)" (Ref: 2024.459). All participants will provide written informed consent in accordance with the Helsinki Declaration and "General Data Protection Regulation (GDPR)". Limitations: Current evidence on madarosis/milphosis is limited, and no validated scales exist for grading eyebrow/eyelash alopecia. Innovations: This study introduces: (1) the first classification scale for chemotherapy-induced madarosis, (2) evidence for cryotherapy as a preventive intervention, and (3) an objective AI-powered photogrammetry methodology.

CHOP Plus Mosunetuzumab as First Line in Patients With Richter´s Syndrome: a Phase II Study of the Spanish Group of CLL

Patients with Richter´s Syndrome received 6 cycle of Mosunetuzumab+CHOP. At the EoI, in patients achieving stable disease (SD) or in patients with partial response (PR) or complete response (CR) who are not candidates to consolidation with cellular therapy, mosunetuzumab as monotherapy will be administered over eleven 21-day cycles (approximately 10 months) or until disease progression or unacceptable toxicity, whichever occurs first.

CRS Questionnaire Validation Project

The objectives of this study are as follows: - Validation of two new questionnaires with the aim of measuring the current perceived condition of a patient with chronic rhinosinusitis in terms of control and severity. - Validation of these questionnaires in routine medical settings. - Evaluation of the results of these questionnaires in comparison with other tools currently available.