Engelskirchen-r�nderoth, Germany

Study of Standard Intensive Chemotherapy Versus Intensive Chemotherapy with CPX-351 in Adult Patients with Newly Diagnosed AML and Intermediate- or Adverse Genetics

Binimetinib Plus Encorafenib Real Life Investigation of Next Generation Melanoma Treatment

Neoadjuvant Ontruzant (SB3) in Patients With HER2-positive Early Breast Cancer: An Open-Label (NeoON)

Real Word European Registry of NTRK Fusions and Other Rare Actionable Fusions (TRacKING)

1. Administrative opening of the center 2. Routine identification of a patients harboring a rare actionable fusion 3. Patient's inclusion - Signature of written informed consent, - Declaration by the physician to the coordinating center (using the "Physician declaration" form) - Completion of the QLQ-C30 questionnaire (at inclusion, at each new treatment and then every 6 months). 4. Collection of retrospective and prospective data into the e-CRF by a local CRA using patients' medical files.

TIGER PRO-Active - Daily Activity, Sleep and Neurocognitive Functioning Study

Glioblastoma (GBM) is the most common malignant primary tumor of the brain with an annual incidence of approximately 3/100.000. Since 2005 the treatment for newly diagnosed GBM consisted of maximal surgical resection, approx. 60 Gy of radiotherapy together with chemotherapy using temozolomide (TMZ), followed by 6 cycles of maintenance chemotherapy. This treatment regimen demonstrated increased median overall survival (OS) from 12.1 to 14.6 months in comparison to surgery and radiotherapy alone in 2005. Since 2005, despite plenty of clinical phase III trials conducted, Tumor Treating Fields (TTFields) therapy was the first treatment shown to significantly increase median progression-free survival (PFS), OS and one to five year survival rates compared to the previous standard of care. These results led to FDA approval of TTFields for newly diagnosed GBM and were acknowledged since then by several guidelines recommending TTFields for GBM therapy (e.g. NCCN guidelines for CNS cancers V.1.2018, RCC guideline tumörer I hjärna och ryggmärg 2020-01-14 V3.0, DGHO guideline for glioma in adults ICD-10 C71 March 2019). Today, several national committees in Europe already list TTFields as reimbursed treatment (e.g. Austria, Sweden, Germany). Data with TTFields therapy in real-world setting is limited and therefore further evaluation of different treatment aspects of TTFields therapy in clinical routine are of interest. In particular the QoL-related aspects neurocognitive functioning, daily activity and sleep quality in this patient cohort is of major interest, given the limited life expectancy with this disease. This non-interventional study aims to investigate change over time in neurocognitive functioning, sleep quality, and activity in daily life as important determinants of QoL in a large cohort of GBM patients in Germany treated with TTFields in routine clinical care using low-threshold, electronic PRO and modern automated tracking data analyses. The gained results will allow even better understanding of TTFields therapy in daily life of GBM patients and consequently, better informing patients about what to expect when starting this therapy, increasing therapy compliance even further in the long-term.

Biomarkers And Neurological Outcome in Neonates 2

Follow-Up on neuro-developmental status of Study participants of BANON1. BANON1 (ClinicalTrials.gov ID: NCT03357250): The aim of the study is to validate the application of combinations of several laboratory parameters in early postnatal blood samples, for identification of infants, who will suffer from early abnormal neonatal neurological outcome, in a population at risk. The population at risk is defined as term and late preterm (>36 weeks of gestation) human infants following perinatal hypoxia-ischemia with or without postnatal resuscitation, and where the combination of laboratory parameters is derived from a preliminary study performed in Turkey (AAMBI) using a metabolomics approach.

BRAF Inhibitor Encorafenib And Cetuximab Real Life Investigation of Next Generation CRC Treatment

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.

ITP Registry and Accompanying Biospecimen Collection

Immune thrombocytopenia (ITP) is a rare hematologic disorder that can lead to a greater risk of bleeding or a prolonged bleeding time due to an autoimmune-mediated deficiency of platelets. In recent years, new treatment options for patients with immune thrombocytopenia have emerged. The results of published clinical studies on ITP can only be used for broad patient care to a limited extent, as they are designed for a patient population with clearly defined inclusion and exclusion criteria. Real world data collected from this registry will help to better understand the diagnosis and therapy of ITP patients in everyday treatment and to more effectively direct individual patients to optimal therapy, thus improving their outcomes. By collecting biospecimens, this project will contribute new knowledge to the study of ITP through standardized, systematic, and high-quality collection and storage of patient samples and associated data. The registry collects clinical data from patients diagnosed with ITP at defined points in the course of the disease. The Data collection includes a range of clinical measures, disease-related factors, treatment/treatment course and outcomes, complications during treatment and Qol, fatigue scoring and survival data (up to 5 years). The data are collected prospectively. In addition, patients can be included retrospectively up to 12 months after the initial diagnosis if continuous documentation can be provided at the treatment centre. In both cases, a written declaration of consent is obligatory.

REscue Stenting With CREDO® Heal for Recanalisation After Unsuccessful Thrombectomy (RECHRUT)

PROVIDENCE - Prospective Non-interventional Study (NIS) to Examine Patient-reported Outcomes and Real-world Clinical Data in Patients With HER2-positive or HER2-low Unresectable or Metastatic Breast Cancer Treated With Trastuzumab Deruxtecan

Eligible participants will be those patients with documented HER2-positive unresectable or metastatic BC receiving T-DXd treatment or patients with documented HER2-low unresectable or metastatic BC receiving T DXd treatment in line with the applicable summary of product characteristics (SmPC) within routine clinical practice. All diagnostic and treatment procedures including visit frequency are at the discretion of the treating physician and not defined by the protocol. T-DXd treatment is considered as a selection criteria. Patients will be informed about use of digital healthcare application (DiGA). Approximately 800 eligible participants will be enrolled which includes 400 patients in the HER2-positive cohort and 400 patients in the HER2-low cohort.