Search results for "escalation"
showing 10 items of 29 documents
Management of febrile neutropenia in the perspective of antimicrobial de-escalation and discontinuation.
2019
Introduction: Infections are among the most frequent complications in patients with hematological and oncological diseases. They might be classified as fever of unknown origin and microbiologically or clinically documented infections. Optimal duration of antimicrobial treatment is still unclear in these patients.Areas covered: We provide an overview on the management of febrile neutropenia in the perspective of antimicrobial de-escalation and discontinuation.Expert opinion: Patients with febrile high-risk neutropenia should be treated empirically with an anti-pseudomonal agent such as piperacillin/tazobactam. Several clinical studies support the assumption that the primary antibiotic regime…
A phase I dose-escalation of trifluridine/tipiracil in combination with oxaliplatin in metastatic colorectal cancer.
2017
TPS3626 Background: Trifluridine/tipiracil, also known as TAS‐102, is a combination of an antineoplastic thymidine‐based nucleoside analogue (trifluridine) and a thymidine phosphorylase inhibitor (tipiracil hydrochloride). The antitumor activity of combined trifluridine/tipiracil and oxaliplatin has been studied in gastrointestinal tumor xenografts, including a 5‐FU resistant subline, using a nude mouse model. This study demonstrated increased antitumor activity for the combination compared to trifluridine/tipiracil or oxaliplatin alone (p < 0.001) (Nukatsuka et al., Anticancer Res 2015). These data support the rationale for clinical use of the combination. We describe a phase 1, intern…
A phase I study of nintedanib combined with cisplatin/gemcitabine as first-line therapy for advanced squamous non-small cell lung cancer (LUME-Lung 3)
2018
Abstract Background There are limited treatment options for squamous non-small cell lung cancer (sqNSCLC) and prognosis remains poor. The safety and pharmacokinetics (PK) of nintedanib, a triple angiokinase inhibitor, plus cisplatin/gemcitabine as first-line treatment for advanced sqNSCLC patients, were evaluated. Materials and methods A phase I, dose-escalation study administering drugs in a 21-day cycle: cisplatin (75 mg/m2, Day 1), gemcitabine (1250 mg/m2, Days 1 and 8) and nintedanib (Days 2–7, 9–21) were given for 4–6 cycles, followed by monotherapy until disease progression or adverse events (AEs). Two nintedanib doses were tested, 150 mg twice daily (bid) and 200 mg bid, to determine…
A Phase I/II Dose-Escalation Multi-Center Study to Evaluate the Safety of Infusion of Natural Killer Cells or Memory T Cells As Adoptive Therapy in C…
2021
Abstract Background: Adoptive cell immunotherapies for opportunistic virus in immunocompromised patients using haploidentical memory T cells have shown to be safe and effective. Since severe cases of COVID-19 present a dysregulated immune system with T cell lymphopenia and a hyper-inflammatory state we have proposed that a similar strategy could be proven to be efficient for COVID-19 patients. This is a study protocol of an open-label, multicenter, double-arm, randomized, dose-finding phase I/II clinical trial to evaluate the feasibility, safety, tolerability, and efficacy of the administration of a single dose of allogenic SARS-CoV-2 specific memory CD45RA - T cells and Natural Killer (NK)…
A new approach to ticagrelor-based de-escalation of antiplatelet therapy after acute coronary syndrome. A rationale for a randomized, double-blind, p…
2021
The risk of ischemic events gradually decreases after acute coronary syndrome (ACS), reaching a stable level after 1 month, while the risk of bleeding remains steady during the whole period of dual antiplatelet treatment (DAPT). Several de-escalation strategies of antiplatelet treatment aiming to enhance safety of DAPT without depriving it of its efficacy have been evaluated so far. We hypothesized that reduction of the ticagrelor maintenance dose 1 month after ACS and its continuation until 12 months after ACS may improve adherence to antiplatelet treatment due to better tolerability compared with the standard dose of ticagrelor. Moreover, improved safety of treatment and preserved anti-is…
A Phase I dose-escalation study of third-line regorafenib with trifluridine/tipiracil in metastatic colorectal cancer
2021
Aim: To determine a recommended Phase II dose of the oral fluoropyrimidine trifluridine/tipiracil (FTD/TPI) combined with the multi-kinase inhibitor regorafenib (REG) in refractory metastatic colorectal cancer patients. Materials & methods: A conventional 3 + 3 dose finding design was used. FTD/TPI was administered on days 1–5 and 8–12 of a 28-day cycle, REG on days 2–22. Two dose levels were used: FTD/TPI 25 mg/m2 b.i.d. + REG 120 mg/d, then escalated to FTD/TPI 35 mg/m2 b.i.d. + REG 120 mg/d. Results: In total, 12 patients were treated at two dose levels. Three dose-limiting toxicities were observed; all were grade 3 hypertension causally attributed to REG. Recommended Phase II dose …
A phase I dose-escalation study of the immunocytokine EMD 521873 (Selectikine) in patients with advanced solid tumours.
2012
Abstract Background EMD 521873 (Selectikine), an immunocytokine comprising a DNA-targeting antibody, aimed at tumour necrosis, fused with a genetically modified interleukin-2 (IL-2) moiety, was investigated in this first-in-human phase I study. Methods Patients had metastatic or locally advanced solid tumours failing previous standard therapy. Selectikine was administered as a 1-hour intravenous infusion on 3 consecutive days, every 3weeks. A subgroup of patients also received 300mg/m 2 cyclophosphamide on day 1 of each cycle. Escalating doses of Selectikine were investigated with the primary objective of determining the maximum tolerated dose (MTD). Results Thirty-nine patients were treate…
Family Matters : Abusing Family Refresh Tokens to Gain Unauthorised Access to Microsoft Cloud Services Exploratory Study of Azure Active Directory Fa…
2022
Azure Active Directory (Azure AD) is an identity and access management service used by Microsoft 365 and Azure services and thousands of third-party service providers. Azure AD uses OIDC and OAuth protocols for authentication and authorisation, respectively. OAuth authorisation involves four parties: client, resource owner, resource server, and authorisation server. The resource owner can access the resource server using the specific client after the authorisation server has authorised the access. The authorisation is presented using a cryptographically signed Access Token, which includes the identity of the resource owner, client, and resource. During the authorisation, Azure AD assigns Ac…
A phase I, open-label, dose-escalation trial of BI 764532, a DLL3/CD3 bispecific antibody, in patients (pts) with small cell lung carcinoma (SCLC) or…
2021
TPS8588 Background: First-line standard of care for pts with metastatic SCLC and neuroendocrine carcinoma (NEC) is platinum-based chemotherapy ± immunotherapy. While the addition of anti-PD1 antibodies has improved outcomes, nearly all pts relapse and prognosis is poor. There is a major unmet need for additional treatment (tx) options. BI 764532 is a delta-like ligand 3 (DLL3)/CD3 T cell engaging bispecific antibody. DLL3 is expressed on the cell surface of many SCLC and NEC tumors, but not on normal cells. In preclinical studies, BI 764532 induced cytotoxicity of DLL3-positive cells and showed anti-tumor activity in animal models. Methods: NCT04429087 is a first-in-human, open-label, dose…
Science in space vs space science: The European utilisation of spacelab∗
1999
Abstract Spacelab is the conventional name given to a manned laboratory to be carried onboard NASA's Space Shuttle, which was built in Europe under the aegis of the European Space Agency (ESA). This paper deals with the initiatives undertaken in Europe to establish a utilisation programme for Spacelab, in particular for its first flight, planned as a joint ESA/NASA demonstration mission. Two main factors will be discussed, which prevented ESA from establishing a sizeable Spacelab utilisation effort. Firstly, owing to the cost escalation of the Spacelab development programme and to NASA's charging policy for access to the Shuttle system, which did not foressee any preferential treatment to E…