Flensburg

PeriPREVENT is a prospective, multi-centre, controlled, open-label, 1:1 randomized superiority trial with two parallel groups. In the intervention group patients will undergo a routine peripheral angiographic intervention (PVI) using a maximally contrast medium sparing strategy with an automated CO2 injection system including iodinated CM as bailout option in case of insufficient image quality or patient's intolerability of CO2 angiography. The control intervention is routine PVI using iodinated contrast media (CM) as standard of care. All patients are followed up until 12 months after the PVI.

This is a Phase III, two-arm, randomized, double-blind, global, multicenter study assessing the efficacy and safety of rilvegostomig compared to pembrolizumab as a 1L treatment for patients with mNSCLC whose tumors express PD-L1.

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 aromatase inhibitor (AI) ± luteinizing hormone-releasing hormone (LHRH) with curative intent according to the current effective local 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 current effective local summary of product characteristics. To understand reasons for treatment decision, and to analyze the clinical adoption of ribociclib + AI ± LHRH after EU approval over time, baseline data will be collected from cohorts of ribociclib + AI ± 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 Austrian 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 + AI ± 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.

This is a prospective observational study to investigate the asthma control and health realted quality of life (HRQL) of benralizumab treated patients in routine clinical practice, their asthma medication intake, and their changes in asthma medication during the study, up to 52 weeks. The asthma control will be analyzed by using the Asthma Control Test (ACT) and the Asthma Impairment and Risk Questionnaire (AIRQ®) at different timepoints during the study period either collected by the investigator or self-reported by the patient. In addition, health realted quality of life will be assessed at baseline and routine follow-up visits using the mini Asthma Quality of Life Questionnaire (miniAQLQ) which is collected by the investigator. To investigate the medication intake and assess the changes in asthma medication, the patients will record their weekly medication intake in a paper-based or an electronic medication diary throughout the study.

This is a trial to evaluate the efficacy, safety, and tolerability of adagrasib plus pembrolizumab plus platinum-doublet chemotherapy versus placebo plus pembrolizumab plus platinum-doublet chemotherapy in participants with previously untreated, locally advanced or metastatic NSCLC with KRAS G12C mutation

The presence of a BRAFV600E mutation is a marker of poor prognosis in patients with mCRC and associated with a median overall survival (mOS) of approximately 12 to 14 months compared to 20 to 25 months for pa-tients with BRAF wild-type tumors. After 1st line therapy, treatment out-comes with standard therapy are poor in patients with BRAF-mutated mCRC, with response rates (ORR) of ≤ 11%, a median progression-free survival (mPFS) between 1.8 and 2.8 months, and a mOS between 4.1 and 6.2 months. Failure to achieve adequate survival outcomes with standard treatment regimens in patients with BRAF-mutated mCRC has encouraged efforts to combine multiple targeted therapies: With 665 randomized patients, the BEACON CRC trial represents the largest trial and is currently the only phase III study in patients with BRAFV600E-mutant mCRC. After a safety lead in for dose confirmation of the triplet regimen, the phase III part was per-formed with a total of 665 patients, randomized 1:1:1 to either receive encorafenib plus binimetinib and cetuximab (triplet) or encorafenib plus cetuximab (doublet) or FOLFIRI / IRI plus cetuximab (control). The BEACON CRC study met its primary endpoints Overall Response Rate (ORR) and Overall Survival (OS) comparing Encorafenib + Binimetinib + Cetuximab vs. Chemotherapy + Cetuximab (ORR: 26 vs. 2%, p\<0.001; OS: median 9.0 vs. 5.4 months, HR 0.52, p\<0.001). The BEACON CRC study was alpha-controlled also for the secondary endpoint comparing Encorafenib + Cetuximab vs. Chemotherapy + Cetuximab in terms of ORR and OS and showed a statistically significant advantage (ORR: 20 vs. 2%, p\<0.001; OS: median 8.4 vs. 5.4 months, HR 0.60, p\<0.001). In terms of safety, the overall frequency of adverse events grade 3/4 was 58% (En-corafenib + Binimetinib + Cetuximab) vs. 50% (Encorafenib + Cetuximab) vs. 61% (Chemotherapy + Cetuximab). Analysis of Quality of Life data resulted in a longer maintenance of Quality of Life in the Encorafenib + Binimetinib + Cetuximab arm and the Encorafenib + Cetuximab arm com-pared to Chemotherapy + Cetuximab. Between Encorafenib + Binimetinib + Cetuximab and Encorafenib + Cetuximab, no relevant differences were reported. With a longer Follow-Up (12.8 months) the updated OS data showed a median OS of 9.3 months in both the Encorafenib + Binimetinib + Cetuximab arm and the Encorafenib + Cetuximab arm compared to 5.9 months in the control arm. Updated ORR rates were 27% in the triplet arm (p\<0.0001 vs. control), 20% in the doublet arm (p\<0.0001 vs. control) and 2% in the control arm. The safety and tolerability were adequate, manage-able and consistent with the known profiles of BRAF-, MEK-, and EGFR-inhibitors. Regarding the triplet combination, the most common adverse events of any grade were diarrhea (triplet: 62%; control: 48%), dermatitis acneiform (triplet: 49%; control: 39%), nausea (triplet: 45%; control: 41%), and vomiting (triplet: 38%; control: 29%). Regarding the doublet combina-tion, the most common adverse events of any grade were nausea (34%), diarrhea (33%), fatigue (doublet 30%; triplet 33%; control 27%) and derma-titis acneiform (29%). The most common updated grade ≥3 adverse events regarding the triplet combination were diarrhea (triplet: 11%; control: 10%), abdominal pain (triplet: 6%; control: 5%), nausea (triplet: 5%; control: 2%,vomiting (triplet: 5%; control: 3%) and intestinal obstruction (triplet 5%; control 3%). With the doublet regimen, the most common updated grade ≥3 adverse events were intestinal obstruction (doublet 5%), asthenia (doublet 4%; triplet 4%; control 5%), fatigue (doublet 4%; triplet 2%; control 5%), diarrhea (3%) and abdominal pain (3%). Based on these data, it is expected that the European Medicines Agency (EMA) will approve encorafenib plus cetuximab for the treatment of adult patients with metastatic BRAFV600E-mutant CRC, who have received prior systemic therapy. Data from pivotal clinical trials are usually based on a selected patient population in order to provide standardized results in the given indication. However, after marketing authorization usage in a broader patient popula-tion is to be expected. Therefore, BERINGCRC - designed as a prospective (allowing initial retrospective documentation), longitudinal, non-interventional study - will investigate the real-world effectiveness, quality of life, safety and tolerability of encorafenib and cetuximab in BRAFV600E-mutant mCRC patients, who have received prior systemic therapy.

The main goal of this trial is to evaluate whether standard skin care supported by a reminder app is superior to standard skin care alone with respect to prevention of grade ≥2 radiation dermatitis in patients receiving adjuvant radiotherapy for invasive breast cancer. Radiation dermatitis will be assessed by an observer (specially trained nurse, technician, or physician) different from the person who performs the routine visit of the patient ("blinded observer concept"), at the start of radiotherapy and weekly during the course of radiotherapy, and at the end of the radiotherapy course (=EOT) according to CTCAE v5.0. Secondary aims include pain (radiation fields), patient satisfaction with the reminder app (Arm A), impact of the reminder app on the use of health technology (Arm A), and benefit from support by staff members and/or the UKSH academy regarding the use of the reminder app (Arm A). This is a multinational, randomized, active-controlled, open-label, multicenter, parallel-group trial, which compares the following treatments of radiation related skin toxicity in patients with breast cancer: Standard skin care supported by a reminder app (Arm A) vs. standard skin care alone (Arm B). Stratification will be done using the following prognostic factors: 1. Treatment volume: Breast or chest wall alone vs. breast or chest wall plus lymph nodes 2. Radiation boost: Yes vs. no 3. At least one risk factor of dermatitis: Yes vs. no Risk factors include chronic inflammatory disease, significant cardiovascular disease, and smoking history of \>10 pack years. After registration, patients will be randomized in a 1:1 ratio to Arm A or Arm B for treatment of radiation related skin toxicity. A stratified block-randomization with random block size will be performed via electronic CRF. The results of the randomization will be visible only after the input of the stratification factors and only for the corresponding patient. This document will be kept at the institution which performs the randomization until the end of the study. Afterwards, the original randomization list will be kept in the trial master file at the trial center of the coordinating investigator for a minimum of 10 years after the final report. The randomization will be performed via electronic CRF centrally by an external company using its standard software. The proceeding for randomization is based on standard operating procedures (SOPs) of this company. Once the randomization is allocated to the patient it cannot be changed. In all patients, radiotherapy will be administered using hypo-fractionation with 40 Gy in 15 fractions of 2.667 Gy given on 5 days per week (overall treatment time = 3 weeks; day of 15th fraction = EOT), preferably with intensity-modulated radiotherapy (IMRT) or volumetric-modulated arc therapy (VMAT). Patients aged ≤50 years receive a sequential radiation boost to the tumor bed of 10 Gy in 5 fractions of 2.0 Gy (on 5 days per week) following whole-breast irradiation, resulting in an overall treatment time of 4 weeks (day of 20th fraction = EOT). This accounts also for patients aged ≥51 years with risk factors for local recurrence. Patients may receive concurrent systemic agents as part of their standard anticancer treatment, regardless of the participation in this trial. These agents may include tamoxifen, aromatase inhibitors, or capecitabine \[10\]. The systemic agents will be indicated and prescribed by treating medical oncologists or gynecologists outside this trial. Regarding dose, type and duration of treatment, contraindications, side effects, pharmacological characteristics and pharmaceutical details of these agents, please see the corresponding product information. Standard Skin Care alone (Arm B): From the start of radiotherapy, standard skin care has to be performed by the patient. This may vary at the participating centers. At the site in Lübeck, it includes fatty cream with 2-10% urea (fatty cream alone, if patients do not tolerate urea) and, in case of pruritus, addition of mometasone furoate cream. In case of grade ≥2 moist desquamation or grade ≥3 radiation dermatitis, each day antiseptic agents will be administered for wound cleansing followed by administration of silicon or calcium alginate bandage. This treatment will be continued until moist desquamation radiation disappears and radiation dermatitis improves to grade 2. Fatty cream with 2-10% urea is applied to the irradiated skin four times daily. Mometasone furoate cream: In addition to the fatty cream with 2-10% urea, mometasone furoate cream (solution 0.1%) is applied to the irradiated skin once daily. Patients of Arm B will be informed about the importance of skin care prior to the start of radiotherapy and reminded during their radiotherapy course, when regularly seen by a radiation oncologist (maximum once a week). Standard Skin Care plus Reminder App (Arm A): From the start of radiotherapy, standard skin care has to be performed by the patient as described for Arm B. In addition, patients of Arm A are supported by a Reminder App, which is developed by the professional company Nextlabel OHG from Lübeck. The purpose of the app is to remind the patients in an intuitive, unobtrusive and supportive way to perform skin care. By default, patients are reminded four times a day, but they will also be able to define a notification schedule that best suits their personal needs. Questionnaire regarding the Reminder App and its impact on the use of health technology: At the end of their radiotherapy course (= EOT), the patients of Arm A will be asked to complete a questionnaire regarding their satisfaction with the Reminder App. In case of a dissatisfaction rate \>20%, the reminder app is considered to require modifications before it can be used in future studies. In case of a dissatisfaction rate \>40%, it will be considered not useful. This questionnaire also includes questions regarding the impact of the app on the use of health technology. Elderly patients aged ≥65 years will be compared to younger patients aged \<65 years to identify potential differences between both age groups and the need for support regarding the use of the reminder app. Sample size calculation The primary goal of this randomized trial is to evaluate whether standard skin care supported by a reminder app is superior to standard skin care alone with respect to preventing grade ≥2 radiation dermatitis during adjuvant hypo-fractionated radiotherapy for breast cancer. According to sample size calculations, 131 patients are required per study arm within the Full Analysis Set. Considering that 2% of patients will not qualify for Full Analysis Set, a total of 268 patients should be randomized. The following analysis sets will be defined for this trial: Safety Analysis Set: All randomized participants who started radiotherapy. Full Analysis Set: All randomized patients who have started either therapy with arm A or with arm B and provide any data on the primary endpoint. The Full Analysis Set will be analyzed according to the Intention-to-Treat principle, i.e. patients will be analyzed in their initial group of randomization. Per Protocol Set: All patients of the Full Analysis Set excluding patients if any of the following criteria are met: * Administration of less than 75% of the planned radiation dose if the reason for discontinuation was any other than death or unacceptable toxicity * More than 50% missing data on the primary study endpoint All patients in the Per Protocol Set will be analyzed within their group of actual treatment received. Statistical analyses: All data recorded in the electronic case report forms describing the study population and toxicity will be analyzed descriptively. Categorical data will be presented in contingency tables with frequencies, percentages and their 95% confidence intervals. Continuous data will be summarized with at least the following: frequency (n), median, quartiles, mean, standard deviation (standard error), minimum and maximum. Number of patients with protocol deviations during the study and listings describing the deviations will be provided. In general, chi-square tests will be used to compare percentages in a two-by-two contingency table, replaced by Fisher´s exact test if the expected frequency in at least one cell of the associated table is less than 5. Stratified two-by-two contingency tables will be analyzed using Cochran-Mantel-Haenszel tests. Logistic regression models serve as multivariable methods for binary endpoint data. Comparison of ordinal variables between treatment arms will be performed using the asymptotic Wilcoxon-Mann-Whitney test, replaced by its exact version in case of ordinal categories with small number of categories and/or sparse data within categories. Any shift in location of quantitative variables between study groups will be performed with the Wilcoxon-Mann-Whitney tests as well. Time-to-event data will be analyzed by Kaplan-Meier methods, when merely non-informative censoring occurs. For statistical comparison, the log rank-test will be provided supplemented by multivariate Cox proportional hazards models. The data analysis will be performed according to the statistical analysis plan (SAP), and which will be finalized prior to database lock and prior to any statistical analysis. To evaluate the rate of patients experiencing grade ≥2 radiation dermatitis during their course of radiotherapy, the worst documented grade during radiotherapy and at EOT is considered, even if patients have missing visits or discontinue radiotherapy prematurely. This reflects the "treatment policy estimand" approach. The rate of patients experiencing grade ≥2 radiation dermatitis will be statistically compared using the Cochran-Mantel-Haenszel Chi-square test on a two-sided significance level of 5%. This test is the natural non-parametric extension of the Chi-square test for testing the treatment effect, while adjusting for the effects of the stratification variables used for randomization. In case of uneven distribution to stratification groups, which may result in very small groups the strata might be pooled for analysis. The decision to pool strata for the analysis will be made before data base lock and before the final analysis of the data. For further assessment of the robustness of the results, a logistic regression model for grade ≥2 radiation dermatitis will be applied including the parameters used for stratification. A model including additional patient characteristics will be fitted for exploratory purposes. The confirmatory evaluation will be performed within the Full Analysis Set; the Per Protocol Set serves for further sensitivity analyses. The visual analogue scale pain prior to radiotherapy, during radiotherapy and at EOT will be subjected to descriptive analyses. pain potential differences in pain between treatment arms, the scores will be subjected to descriptive analysis. For graphical visualization Box-Whisker diagrams will be provided. Moreover, the change from baseline values will be considered and subjected to descriptive analyses. Friedman tests and Wilcoxon-Mann Whitney tests may be applied for comparison of study visits. At the EOT-visit, patient satisfaction with the reminder app in arm A will be evaluated and subjected to standard statistical methods. In case of a dissatisfaction rate \>20%, the reminder app needs modifications. In case of a dissatisfaction rate \>40%, it will be considered not useful. In addition, the questions on the impact of the app on the use of health technology will be evaluated descriptively. Elderly patients aged ≥65 years will be compared to younger patients aged \<65 years to identify potential differences between both age groups and the need for support regarding the use of the reminder app. Standard statistical tests serve as a tool for exploratory comparison of age groups.

The GMALL registry serves the purpose of ALL research and quality assurance. The Registry collects data about diagnostics, treatment and outcome of Adult ALL Patients in the clinical routine, whether or not the patient is treated within a clinical trial.

Prospective, multicentre, randomised, parallel group, open, phase III clinical trial for a maintenance therapy, for patients who underwent an induction therapy and autologous stem cell transplantation (ASCT) in the GMMG-HD8/DSMM XIX trial or a similar quadruplet induction/consolidation therapy regimen followed by at least one ASCT. Investigational Medicinal Product: Iberdomid (oral), isatuximab (subcutaneous administration via a wearable injector system). Randomisation will be performed centrally by GMMG/DSMM offices after verification of the eligibility of the patient. At the time of study inclusion, randomization will be performed into arm A (iberdomide) or arm B (iberdomide + isatuximab). Randomization will be stratified by centrally assessed MRD negativity status (yes vs. no vs. unknown); assessed by NGF from BMA; sensitivity of 10\^-5; independent of standard IMWG response) and number of HDM/ASCT (single vs. tandem). Patients randomized in arm A will receive 39 cycles of the drug iberdomide, a Cereblon E3 Ubiquitin Ligase Modulating Drug (CELMoD®) that shares structural similarities to the immunomodulatory compounds (IMiDs) such as thalidomide and lenalidomide. Each cycle will last for 29 days. Patients in arm B will receive the same the 39 cycles of iberdomide plus monoclonal anti-CD38 antibody isatuximab subcutaneously. In both arms, patients will receive 20 mg dexamethasone in cycle 1, on the same days as the isatuximab administration in Arm B. End of study will be after 36 months of the maintenance therapy. There is one primary objective: \- Demonstration of superiority of iberdomide plus isatuximab compared to iberdomide with respect to bone marrow minimal residual disease (MRD) negativity rates (sensitivity 2x10\^-6 via next-generation flow cytometry \[NGF\]) after two years of maintenance therapy. There is one key secondary objective: \- PFS, defined as time from randomization to disease progression or death from any cause, whichever occurs first. Further secondary objectives are: * Rates of sustained MRD negativity (at sensitivity levels of 10-5 and 2x10\^-6 via NGF from BMA) after 1, 2 and 3 years of maintenance therapy. * Conversion from MRD positive to negative (at sensitivity levels of 10\^-5 and 2x10\^-6 via NGF from BMA). * Rates of best overall response to treatment (BOR). * Rates of partial response (PR), very good partial response (VGPR), complete response (CR) and stringent complete response (sCR). * Time-to-next-treatment (TTNT). * PFS on subsequent line of therapy. * Overall survival (OS). * Improvement of IMWG response categories (PR, VGPR, CR, sCR). * Proportions of patients in both treatment arms maintaining BOR and CR from baseline. * Assessment of quality-of-life (QoL) via the EORTC-QLQC30, EORTC-QLQMY20, and EQ-5D-5L questionnaires.

The standard treatment for patients with acute myeloid leukemia (AML) with an abnormality in the IDH1 gene, who are not eligible for intensive chemotherapy, is a combination of ivosidenib and azacitidine. In this study it is investigated whether adding venetoclax to the standard treatment can improve the outcome of the treatment of this specific form of AML. The safety is investigated and how well it works. In order to properly assess the value of venetoclax, the effect of venetoclax is compared with the effect of a placebo. A placebo is a product without an active ingredient, a 'fake medicinal product'.