Antakya Hatay, Turkey

A Non-interventional Study for Kisqali (Ribociclib) in Combination With an Aromatase Inhibitor for Adjuvant Treatment in Patients With HR+/HER2- Early Breast Cancer at High Risk of Recurrence

This non-interventional study aims to provide information on real-world effectiveness, safety and tolerability, management of adverse events, QoL and patient compliance of patients with HR+/HER2- early breast cancer at high risk of recurrence treated with ribociclib in combination with an non-steroidal aromatase inhibitor (NSAI) ± luteinizing hormone-releasing hormone (LHRH) with curative intent according to the German summary of product characteristics. In order to put the results of patients treated with ribociclib into perspective, socio-economic data, data on QoL and patient compliance will also be collected from patients treated with abemaciclib + endocrine therapy (ET) ± LHRH as described in the respective local summary of product characteristics. To understand reasons for treatment decision, and to analyze the clinical adoption of ribociclib + NSAI ± LHRH after EU approval over time, baseline data will be collected from cohorts of ribociclib + NSAI ± LHRH, abemaciclib + ET ± LHRH, and additionally from patients treated with ET monotherapy ± LHRH and analyzed cross-sectionally. The study is planned to be rolled out into a broad set of German and optionally Austrian and Swiss breast centers and gynecological practices to describe clinical routine in a representative subset of the local healthcare eco-system. It will gather insights into the potential benefits and risks associated with ribociclib + NSAI ± LHRH in the adjuvant treatment of HR+/HER2- eBC patients at high risk of recurrence. This knowledge will inform about clinical decision-making and contribute to improved patient outcomes in routine practice.

Adjusted High-dose Chemotherapy with Autologous Stem Cell Transplant Vs. Conventional Immunochemotherapy in Elderly PCNSL Patients

Primary diffuse large B-cell lymphoma of the central nervous system (PCNSL) is a rare lymphoma affecting only the central nervous system compartment. PCNSL patients are typically 60 years or older and have poor prognoses. However, there are alternative treatment approaches to consider with the potential to improve medical outcomes for this patient population. The current standard of care in Germany and many international centres for patients 65 and older is treatment with R-MP, comprising rituximab, high-dose methotrexate (HD-MTX) and procarbazine followed by maintenance therapy with procarbazine. An alternative approach comprised of a shorter induction treatment with rituximab, HD-MTX and cytarabine (MARTA) followed by age-adjusted high-dose chemotherapy and autologous stem cell transplantation (HCT-ASCT) was recently shown to be feasible and effective in elderly PCNSL patients considered eligible for high-dose chemotherapy requiring autologous stem cell transplantation. Nevertheless, data evaluating this short duration treatment approach remains scarce, and randomized trials have not yet been published. The objective of the PRIMA-CNS trial is to demonstrate that intensified chemotherapy followed by consolidating HCT-ASCT is superior to conventional chemotherapy with R-MP followed by maintenance with procarbazine in elderly patients with newly diagnosed PCNSL; not only regarding survival and remission after treatment but also regarding standards like quality of life (QOL) and treatment related morbidities. Results of this randomized trial will either change the standard of care to an intense and shorter treatment approach or re-define R-MP as a proven treatment standard. In addition, a geriatric assessement is implemented in this trial with the goal to better define transplant eligibility. If this trial shows the superiority of HCT-ASCT, the investigators will establish an improved treatment standard with increased chances for long-term remission and cure and reduced frequency and length of chemotherapy treatment. Considering the poor prognosis of this patient population, this randomized phase III trial is of great clinical importance to provide patients, the patients' families and care takers with optimal treatment.

A Study to Learn About How Safe BAY 3389934 is, Its Suitable Dose, and How it Affects the Participants With Sepsis Induced Coagulopathy

The Dragon PLC Trial (DRAGON-PLC)

Primary liver cancer (PLC) is the third most common cause of cancer death worldwide. Surgical resection is the mainstay for a curative approach as contemporary chemotherapy and immune-based therapies only lead to a median survival of 10-14 months. A complete surgical resection increases the median survival to 42 months (range 32-52 months). However, PLC is mainly diagnosed at an advanced stage and >70% of PLC patients are ineligible for an immediate surgical approach. There are different reasons that make a patient ineligible for surgery, one important reason is the risk of liver failure after the surgery due to a small remnant liver. This study aims to improve the oncological, radiological and surgical strategy to allow more patients to undergo liver resection safely, to improve quality of life and to extend overall survival at acceptable costs. Adequate function of the future liver remnant (FLR) is a prerequisite for surgical resectability. This is necessary in order to avoid liver failure after surgery, a major cause of morbidity (38%) and mortality (27%). To mitigate this risk, regenerative strategies based on preoperative calculation of the FLR volume and function are essential. Patients with technically resectable disease but predicted insufficient FLR volume or function are referred to as primarily unresectable or potentially resectable (PU/PR). These patients can undergo strategies that capitalize on the regenerative capacity of the liver which aim to preoperatively increase the FLR volume and function in order to allow surgery. Many of the patients that are primarily unresectable due to an insufficient FLR can become ultimately and safely resectable after the induction of adequate FLR-hypertrophy by the current standard, portal vein embolisation (PVE). However, 25% of patients do not show sufficient FLR growth after PVE and are unable to safely undergo resection. A new approach has been developed to improve this. Combined portal and hepatic vein embolisation (PVE/HVE) has great promise in terms of increasing FLR growth, resection rate (RR), safety and potentially, overall survival. Establishing PVE/HVE as the new standard could result in increased survival and a better quality of life (QoL) for patients.

The Study Aims to Measure the Metabolome in Melanoma Patients Using NMR Spectroscopy and Gas Chromatography and to Analyse Differences Depending on the Course of the Disease.

SUPRAME-ACTengine® IMA203 vs. Investigator's Choice of Treatment in Previously Treated, Unresectable or Metastatic Cutaneous Melanoma

SCREENING: Patient eligibility will be determined by protocol inclusion/exclusion criteria including HLA (human leukocyte antigen) screening. Leukapheresis for potential manufacturing of the IMA203 cellular product may be performed, if patients are HLA-A*02:01 positive and meet the eligibility criteria for leukapheresis. MANUFACTURING: IMA203 products will be made from the patients' white blood cells. TREATMENT- Experimental arm: Lymphodepletion with cyclophosphamide and fludarabine will occur in the days before the IMA203 product infusion to improve the duration of time that IMA203 product stays in the body. The patient will be admitted to the hospital during the T-cell infusion. After the IMA203 product infusion, a low dose of IL-2 will be given subcutaneously for up to 10 days. TREATMENT- Control arm: Investigator's choice of treatment approved by the respective competent authority (nivolumab plus relatlimab [Opdualag®], lifileucel, nivolumab, pembrolizumab, ipilimumab, or chemotherapy [e.g., dacarbazine, temozolomide, paclitaxel, alb-bound paclitaxel, or paclitaxel plus carboplatin]) as determined by the site investigator in accordance with current respective prescribing information (PI) and/or summary of product characteristics (SmPC).

A Phase III Renal Outcomes and Cardiovascular Mortality Study to Investigate the Efficacy and Safety of Baxdrostat in Combination With Dapagliflozin in Participants With Chronic Kidney Disease and High Blood Pressure

The purpose of this study is to investigate the efficacy, safety, and tolerability of baxdrostat in combination with dapagliflozin, compared with placebo and dapagliflozin, in reducing the risk of the composite of > 50% decline in eGFR, kidney failure, or CV death, in individuals with CKD and HTN. This study consists of a 4-week dapagliflozin Run-in Period for participants untreated with SGLT2i at screening, and a double-blinded period where participants will receive either baxdrostat/dapagliflozin or placebo/dapagliflozin. Site visits will take place at 2-, 4-, 8-, 16-, 34, and 52-weeks following randomisation. Thereafter visits will occur approximately every 4 months. The study closure procedures will be initiated when the predetermined number of primary endpoint events is predicted to have occurred ie, the PACD. All randomised participants including any participants who have prematurely discontinued study intervention will be scheduled for a SCV within a few weeks of the PACD. This period can be extended by the Sponsor. In case of premature discontinuation of blinded study intervention, participants will continue in the study and receive dapagliflozin 10 mg, unless the participant meets dapagliflozin specific discontinuation criteria. If study intervention is temporarily or permanently discontinued, the participant should remain in the study, and it is important that the scheduled study visits (including the PTDV for participants with permanent discontinuation of study intervention) and data collection continue according to the study protocol until the SCV.

A Study of Zasocitinib in Adults With Psoriatic Arthritis Who Have Not Taken Biologic Medicines

FIH Trial of VERT-002 in Patients With Locally Advanced or Metastatic Solid Tumors With MET Alterations

Assessing Habitual, Goal-Directed, and Pavlovian Influences in Alcohol Use Disorder

This project has three research aims: 1. Investigate whether stronger habitual behavior and increased susceptibility to the conflict between habitual and goal-directed control are associated with SUD 2. Investigate whether PIT is more of a habitual or a goal-directed process. 3. Replicate the previous findings that moderate to severely dependent AUD patients show a stronger PIT effect in contrast to the control group The experiment will be conducted in 90 AUD patients and 90 age and gender-matched controls. Participants will perform the AST task over two consecutive days, and during the second day, they will also perform the single-lever PIT task. In the AST, participants need to press four keys according to the cue location; two keys are associated with high reward, while the other two are associated with low reward in case of correct and timely responses. The explicit goal is to maximize the reward. While in half of the trials the cues are presented in a random order, in the other half of the trials, participants repeatedly perform a fixed action sequence of 12 elements (habit condition). The degree of action sequence chunking (i.e. automation) is assessed via the differences in error rates and reaction times between the random and fixed order condition (habit parameter). Importantly, 15% of all trials are dual- target trials. In these, the goal-directed system (press high reward key) and the action sequence (press sequence key) can either be in line (congruent trials) or in conflict (incongruent trials) with each other. Thus, the interference between goal-directed and habitual control can be tested. The single-lever PIT task consists of four phases. In the instrumental task, participants need to learn which shells to collect or leave in order to gain as much money as possible; the correct choice is probabilistically rewarded in 80% of all times. During the Pavlovian conditioning phase, colorful fractals are presented in the back of the screen, which have been passively paired either with monetary loss, no change or monetary gain, i.e. they act as positively valued, neutral or negatively valued cues. During the transfer phase, participants were instructed to perform the instrumental task as they have done previously. These fractals thus act as independent, Pavlovian conditioned background stimuli and interact with instrumental behavior in the unrelated task to collect the correct shells. To avoid further learning, this transfer part will be conducted under nominal extinction. Finally, query trials, in which one of two pictures will have to be chosen, will be used to assess the relative cue value. The participants will additionally perform a Counting Stroop task and a No-go Simon task. In the Stroop task, either one, two, three or four identical digits from 1 to 4 are shown. Number and denotation of digits are either congruent (1, 22, 333, 4444; 80 trials) or incongruent (111, 2222, 3, 44; 80 trials). Subjects have to indicate how many digits were shown. In the No-go Simon task, the investigators will show arrows either pointing to the left or right. The arrow can either be shown on the left or the right side of the display. In congruent trials, direction and position are the same, whereas they differ in incongruent trials. Participants have to indicate the direction of the arrow and ignore the position. 20% of trials are No-go trials, indicated by bold arrows. Here subjects have to always withhold a response (inhibition task). Expected results: Hypothesis a: The investigators hypothesize an increased habitual tendency and susceptibility to conflict, i.e. interference between habitual and goal-directed control as assessed with the AST in AUD participants. More specifically, the investigators hypothesize that the AUD participants will perform the fixed sequence faster and with fewer errors on the second day of AST. Moreover, in contrast to the control group, AUD participants will choose the high reward keys less often in incongruent trials (when the goals-directed control and the habitual action sequence are in conflict with each other), indicating a shift from goal-directed to habitual control. Hypothesis b: Given that the allocation of top-down control is needed for overcoming interference by Pavlovian cues and exhibiting more goal-directed control, the investigators expect that participants with stronger PIT effect (lower interference control) also acquire habits more easily and show increased habitual control. Additionally, the investigators hypothesize that the participants with a higher PIT effect will exhibit a shift from goal-directed to habitual control, as indicated by a lower frequency of high reward keys in incongruent trials. As a general process, these associations should be observable in both, the AUD and the control group. Hypothesis c: As a replication, the investigators expect the AUD group to show a stronger PIT effect in contrast to the control group. Hypothesis d: Both Interference costs (i.e. increased ER in instrumental responses) during PIT and interference costs between goal-directed and habitual behavior will be associated with interference costs at the stimulus level (Stroop task) and at the response level (No-go Simon task), and these costs will also be correlated with the ER during response inhibition (No-go Simon task).