Hyogo, Akashi, Japan

Cisplatin (CIS) Administered As Dry Powder for Inhalation (DPI) in Patients with Stage IV Non-Small Cell Lung Cancer

The survival of patients with metastatic lung cancer has significantly improved with platinum-based treatments and, more recently, with targeted therapies and immunotherapies. However, despite therapeutic advances, lung cancer remains the world's leading cause of cancer-related death (approximately 2 million per year), due to innate or acquired tumour resistance to treatments. The combination of chemotherapy (platinum-doublets) and immunotherapy (immune checkpoint inhibitors) shows promising results in terms of overall survival (OS) and progression-free survival (PFS) for the treatment of first-line stage IV non-small cell lung cancer (NSCLC) patients, leading to such combinations becoming a real backbone of the Standard of Care (SoC) for NSCLC patients. These results may be attributable to the immunogenic effects of chemotherapy-induced tumour cell death, which, when used with immune checkpoint inhibitors, is an approach that may improve the clinical outcomes of cancer patients. However, conventional chemotherapy's severe systemic toxicities represent a limiting factor in terms of administered dose and frequency, requiring long rest phases (i.e., interruption of treatment) leading to a relatively limited frequency of chemotherapy treatment in current clinical practice (4 to 6 cycles of intravenous (iv) administration, all separated by a 3-week interruption period). This limitation, associated with high mortality, especially in the advanced stages of lung cancer, demonstrates that the treatments/combinations currently used are far from optimal. Administration of cisplatin by inhalation (pulmonary route) is a promising additional approach that may overcome the limitations of conventional chemotherapy and increase the efficacy of the current SoC via sustained local attack on the lung tumours of patients treated using immune checkpoint inhibitors with or without iv chemotherapy. Use of a dry powder inhaler (DPI) enables a high therapeutic response by delivering high local concentrations of a well-established active substance without the usual undesired reactions that limit the use of high doses when administered through the conventional systemic route. Thanks to limited systemic exposure to the cytotoxic active ingredient with the use of a dry powder inhaler, such add-on treatment enables considering 5 times weekly administration of inhaled chemotherapy at the patient's home. Increasing the frequency of local chemotherapy treatment in this way may enhance activation of the systemic anti-tumour immune response via local activation and stimulation of tumour-specific antigen release as a result of a safe, sustained and prolonged local effect, compared to the peak/short effect of iv chemotherapy. This study may provide insights into whether this add-on treatment might be a safe option for NSCLC patients.

Testing and Evaluating a Psychoeducation Tool and Guidelines for Victims of Violence in Belgian Hospitals.

A Global Phase III Study of Rilvegostomig or Pembrolizumab Plus Chemotherapy for First-Line Treatment of Metastatic Non-squamous NSCLC

This is a Phase III, two-arm, randomized, double-blind, global, multicenter study assessing the efficacy and safety of rilvegostomig compared to pembrolizumab, both in combination with platinum-based doublet chemotherapy, as a 1L treatment for patients with non-squamous mNSCLC whose tumors express PD-L1 (TC ≥ 1%).

A Global Phase III Study of Rilvegostomig or Pembrolizumab Plus Chemotherapy for First-Line Treatment of Metastatic Squamous Non-small Cell Lung Cancer (NSCLC)

This is a Phase III, two-arm, randomized, double-blind, global, multicenter study assessing the efficacy and safety of rilvegostomig compared to pembrolizumab, both in combination with platinum-based doublet chemotherapy, as a first-line (1L) treatment for patients with squamous metastatic non-small cell lung cancer (mNSCLC) whose tumors express PD-L1 (tumor cells (TC) ≥ 1%).

A Study to Evaluate the Efficacy and Safety of Inavolisib in Combination With Phesgo Versus Placebo in Combination With Phesgo in Participants With PIK3CA-Mutated HER2-Positive Locally Advanced or Metastatic Breast Cancer

Safety and Efficacy of MSC-EVs in the Prevention of BPD in Extremely Preterm Infants

Bronchopulmonary Dysplasia (BPD) is a chronic severe multifactorial respiratory disease that affects extremely premature infants and is the most common and severe consequence of preterm birth. BPD is associated with disrupted alveolarization and microvascular development, resulting in abnormal gas exchange and lung mechanics. BPD has a multifactorial aetiology, with pre-, peri-, and postnatal mechanisms causing inflammation and injury and resulting in the disruption of the lung's development with the insurgence of an aberrant repair mechanism. EXOB-001 consists of a population of EVs smaller than 0.22 μm in diameter, containing proteins and nucleic acids, enclosed in a double layer of phospholipids with integral and surface-bound proteins as the main components. EVs exert anti-inflammatory and immunomodulatory activity by reducing the release of proinflammatory cytokines and reducing the recruitment of immune cells in the lung. Current evidence shows that EVs can modulate macrophage phenotype, and this is relevant for BPD, because of the role macrophages have in its pathogenesis. Two hundred sixty-five (265), 40 in phase 1 (to reach 36 evaluable subjects) + 225 in phase 2 (to reach 203 evaluable subjects), extremely preterm infants at risk of developing BPD with 23 weeks up to 28 (27 weeks+6 days) weeks of gestational age and birth weight between 500g and 1,500g and being endotracheally intubated between postnatal day 3 and day 10 receiving mechanical ventilation with FiO2 > 25%. Phase 1 will start with cohorts with a single administration starting with a low dose up to a high dose and thereafter start the escalation of cohorts with 3 administrations starting with a low dose up to a high dose. In the case of 3 endotracheal administrations, there will be a window of 24 hours between the administrations (the maximal duration of the treatment with EXOB-001 will be 48 hours). Phase 2 includes 2 groups with selected dosage levels and regimen of EXOB-001 based on phase 1 interim results. Subjects will be randomised (2:2:1) to receive either EXOB-001 or placebo (saline solution).

Study BT8009-230 in Participants With Locally Advanced or Metastatic Urothelial Cancer (Duravelo-2)

A Study of Dostarlimab vs Placebo After Chemoradiation in Adult Participants With Locally Advanced Unresected Head and Neck Squamous Cell Carcinoma

PoCUS Diagnostic Accuracy for Fecal Impaction in the Emergency Department: a Prospective Study

Background Many medical specialties and paramedical fields are increasingly using point-of-care ultrasound (PoCUS). PoCUS is a pillar of clinical evaluation along with inspection, palpation, percussion, and auscultation, and it has become essential in daily clinical practice, as it enhances differential diagnosis. In a position statement published in 2015, the American Academy of Emergency Medicine followed by the European Federation of Societies for Ultrasound in Medicine and Biology in 2016 recommended the inclusion of PoCUS in the curricula of medical schools to improve the learning of core concepts and enhance students' understanding of physical examinations. The integration of PoCUS into clinical examination raises the issue of PoCUS diagnostic accuracy. In everyday practice, fecal impaction is defined as the accumulation of hard fecal matter in the rectum and colon, with the absence of spontaneous evacuation. Its annual prevalence is estimated at 47.3% in nursing homes, affecting approximately 70% of nursing home patients. Furthermore, 42% of patients admitted to geriatric services suffer from fecal impaction. In the United States, 21.9% of patients admitted to the emergency department (ED) with fecal impaction died in hospital, and severe morbidity was identified in 40.6% of patients. Over 90% of the patients with fecal impaction who visited the ED subsequently required hospitalization. In 2011, there were 42,000 ED visits in the US for fecal impaction, with patients aged over 65 being the most affected. It is widely known that the incidence of fecal impaction increases with age and impairs quality of life in patients over 65 years of age. This common problem is often undiagnosed and thus frequently left untreated, whereas its prompt identification and treatment minimize the risk of complications. The most frequent symptoms are false diarrhea, fecal incontinence, behavioral disorders (agitation, delirium), loss of appetite, nausea, vomiting, abdominal pain, and electrolyte disorders. The site of impaction is most often rectal in 66.4% of cases. Fecal impaction is the most frequent cause of diarrhea in the elderly, with an incidence of 55%. Currently, in the ED, fecal impaction is diagnosed by plain abdominal X-rays or abdominal computed tomography (CT) scans if required as part of the ED investigations. PoCUS is a valuable tool for investigating suspected fecal impaction, as it can guide the investigator to make a rapid diagnosis, thus leading to its rapid management. To analyze the presence of fecal impaction using PoCUS, the patient should be supine and comfortable. In the case of fecal retention in the rectal lumen, ultrasound waves are reflected from the surface of the contents at a depth deeper than the bladder (anechoic area), with a hyperechoic area with a half-moon shape being depicted in the transverse ultrasound image. In addition, with hard stool accumulation, an acoustic shadow appears in the transverse ultrasound image of the crescent-shaped hyperechoic area. By contrast, in the absence of fecal retention or gas in the rectal lumen, no obvious hyperechoic area is depicted. In the transverse ultrasound image, a circumferential hypoechoic area may be observed as an empty intestine. The main objective of this study is to evaluate the contribution of PoCUS to the clinical examination of patients coming to the ED with clinical suspicion of fecal impaction. Trial design This study is an interventional multicentric prospective study aiming to evaluate PoCUS diagnosis accuracy in patients aged 75 years or older presenting to the ED with suspected fecal impaction while taking a plain abdominal x-ray (or abdominal CT scan if required for the ED investigations) as the reference diagnostic investigation. Inclusion process The emergency physician in charge of the eligible patients with suspected fecal impaction will advise the investigator before ordering a plain x-ray. The investigator will assess the patient's eligibility, explain the study, and obtain signed informed consent. She or he will then verify the inclusion and exclusion criteria and initiate the study process. Intervention process The investigator is independent of the patient medical management. She or he will perform an abdominal ultrasound in search of fecal impaction. PoCUS images will be recorded according to the procedures of the study centers and their capacities in terms of the ultrasound equipment. The investigator will complete a case report form (CRF) stipulating the presence or absence of fecal impaction (Appendix 1). The diagnosis of fecal impaction will be made based on a plain abdominal x-ray (or abdominal CT scan if required as part of the ED investigations). In the case of a positive x-ray, the emergency physician will perform a digital rectal examination to determine the consistency of the fecal impaction (hard or soft) and initiate the appropriate treatment. Evaluation process A research associate will record the anonymous CRF data on a dedicated computerized database (REDCAP). Based on the recorded data, the diagnostic accuracy of PoCUS for fecal impaction will be determined. Sample size The sample includes patients aged 75 years or over presenting to the ED with suspected fecal impaction. The diagnostic value of clinical or radiological ultrasound for fecal impaction is not precisely known. Based on a 42% prevalence of fecal impaction in elderly patients, a sample of 247 patients is required to obtain a 95% confidence interval for an expected sensitivity of 95%, assuming an attrition rate of 10%. Statistical method The software IBM SPSS statistics 26.0 (SPSS Inc., Chicago, IL, USA) will be used to analyze the data. Continuous variables describing the study population will be detailed using medians, standard deviations, and minimum and maximum values. Discrete variables will be reported by category as numbers and percentages. The χ² test of independence will be used to compare discrete variables. The Wilcoxon-Mann-Whitney test will be used to compare continuous variables. The significance level corresponds to a p-value of 0.05 or less. The 95% confidence intervals will be calculated using the mid-p exact value. Data management Data collection All the data relating to this study will be collected on paper CRF by the study investigator. Collected data will concern the clinical situation, patient characteristics, test results, and diagnostic approach associated with the coefficients of certainty of the physicians in charge as well as any questions relating to the bedside PoCUS. Any missing data will be collected from the medical file by the inclusion center's principal investigator, coordinating investigator, or research associates. Patients will initially be identified on the CRF by their last name, first name, date of birth, file number from the institution where they were included, and an identification number of the study. This identification number will be comprised of a reference for the inclusion center and participant number. After the principal investigators or research associates complete the collection of missing data, patients will henceforth only be identified by their study identification number to anonymize the data. Data will be recorded on REDCAP. Data access A list of correspondence between the study identification number and the other identifying data will be kept under the responsibility of the project promoter. This list is kept for the statutory period of time provided for this type of research. The protection of patients' personal data will be guaranteed by the European General Data Protection Regulation of April 27, 2016 (in application since May 25, 2018), the Belgian Law of July 30, 2018, on privacy protection with regard to the processing of personal data, and the Belgian Law of August 22, 2002, on patient rights. Certified good clinical practice will be used with a compliant electronic data management system. The system is connected to the clinical center database management system, thus restricting access to authorized users. This distinguishes between users and guarantees data safety. Any individual with direct access to the data will take all the necessary precautions to ensure the confidentiality of the information relating to participants included in the study, particularly regarding their identity and results. Any individual with direct access to data will be subject to professional secrecy. They will undertake to never divulge the confidential information relating to the study participants and to guarantee the anonymization of the data before transferring it to the database manager and biostatistician. Any data disclosure required by the law or applicable regulations will be done if necessary. Data storage After completing the data collection and anonymization, the data will be added to a file (SPSS 26.0) with access restricted by a password. This document will be owned by the project promoter represented by the study coordinator. This person ensures that the documents and data relating to the research are kept for 20 years in accordance with the applicable regulations. Coordinating investigators are responsible for keeping the essential study documents at the research site. If they leave the institution, they will delegate this responsibility to the project promoter in writing. Ethics Written documentation explaining the PoCUS procedure and the risks or benefits of undergoing PoCUS will be given to all participants. They will also receive an explanation of data protection. Ultrasound technology does not put participants at risk during abdominal ultrasound. Indeed, physicians are required to observe the ALARA (as low as reasonably achievable) principle during clinical examinations. Signed written consent to participate in this study will be collected for each participant as recommended by the Additional Protocol to the Convention on Human Rights and Biomedicine concerning Biomedical Research as well as by the Council of Europe's Steering Committee on Bioethics. A study file including this protocol, a research summary, and the CRF will be submitted to the ethics committees of each participating center. The research protocol will only begin if a favorable opinion is granted by the local ethics committees as well as the ethics committee of the main center. Any substantial changes made to the study file must be approved by the study promoter. Before making any changes, all the ethics committees will need to give their approval. The project promoter will communicate the study end date to the ethics committees within a delay of 90 days. This date will correspond to the date of the last inclusion or, if appropriate, to the theoretical end date of the study in this protocol. If the inclusion number is not reached within 6 months, an extension request will be added to the protocol. Compensation No compensation is given to the participants of this study. Adverse event An adverse event is any untoward medical occurrence in a patient, including the exacerbation of an existing condition that is not necessarily related to the study itself. Any incidental findings using PoCUS will be reported, and information will be forwarded to patients under medical confidentiality. The family physician will also be notified by telephone and in a consultation letter from the ED. All the results will be recorded confidentially in the patient's medical file. The reasons for losing participants to follow-up will also be mentioned. This is a clinical study. PoCUS is a non-invasive procedure for which no risks have been reported in the current literature. In this study, patient management will always take priority over performing PoCUS. Insurance Regarding the Belgian law of May 7, 2004, the project promoter will take out insurance to cover any risk incurred by the study participants.

A Study To Evaluate The Efficacy And Safety Of Ifinatamab Deruxtecan (I-DXd) In Subjects With Recurrent Or Metastatic Solid Tumors (IDeate-PanTumor02)

This study will evaluate the efficacy and safety of I-DXd in participants with recurrent or metastatic solid tumors previously treated with 1 or more systemic therapies for the selected tumor indication. The study will be divided into 2 parts: Stage 1 and Stage 2. Each cohort starts with Stage 1 and may continue to Stage 2 if sufficient safety and efficacy data are observed. The HCC Safety Run-In (Phase 1) will assess the safety and tolerability of I-DXd in participants with HCC.