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000304497 1001_ $$aRauber, Conrad$$b0
000304497 245__ $$aProtocol: Faecal microbiota transfer in liver cancer to overcome resistance to atezolizumab/bevacizumab - a multicentre, randomised, placebo-controlled, double-blind phase II trial (the FLORA trial).
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000304497 520__ $$aCombined vascular endothelial growth factor/programmed death-ligand 1 blockade through atezolizumab/bevacizumab (A/B) is the current standard of care in advanced hepatocellular carcinoma (HCC). A/B substantially improved objective response rates compared with tyrosine kinase inhibitor sorafenib; however, a majority of patients will still not respond to A/B. Strong scientific rationale and emerging clinical data suggest that faecal microbiota transfer (FMT) may improve antitumour immune response on PD-(L)1 blockade. Early trials in melanoma with FMT and reinduction of immune checkpoint blockade (ICI) therapy in patients with anti-PD-1-refractory metastatic melanoma were reported in 2021 and demonstrated reinstatement of response to ICI therapy in many patients. Due to anatomical vicinity and the physiological relevance of the gut-liver axis, we hypothesise HCC to be a particularly attractive cancer entity to further assess a potential benefit of FMT in combination with ICI towards increased antitumour immunity. Additionally, HCC often occurs in patients with liver cirrhosis, where liver function is prognostically relevant. There is evidence that FMT may increase hepatic function and therefore could positively affect outcome in this patient population.This prospective, multicentre, randomised, placebo-controlled, double-blind phase II clinical trial has been designed to assess immunogenicity and safety of FMT via INTESTIFIX 001 combined with A/B in advanced HCC in comparison to A/B with placebo. Primary endpoints are measured as tumour CD8+ T cell infiltration after 2 cycles of treatment with vancomycin, A/B+INTESTIFIX 001 in comparison to vancomycin-placebo, A/B+INTESTIFIX 001-placebo and safety of the therapeutic combination in advanced HCC. INTESTIFIX 001 is an encapsulated FMT preparation by healthy donors with a high alpha-diversity in their gut microbiome for oral administration, manufactured by the Cologne Microbiota Bank (CMB). Sample size was calculated to achieve a specific expected accuracy for the primary immunological endpoint. 48 subjects will be randomised to reach a goal of 42 usable measurements in the modified intention-to-treat set. Subjects will be randomised in a 2:1 ratio to A/B or placebo (28 A/B, 14 placebo).The study was approved by ethics committee review and the German Federal Ministry of Drugs and Medical Devices. The trial is registered under EU CT no. 2023-506887-15-00. The outcome of the study will be disseminated via peer-reviewed publications and at international conferences.NCT05690048.
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000304497 650_7 $$2Other$$aCHEMOTHERAPY
000304497 650_7 $$2Other$$aClinical trials
000304497 650_7 $$2Other$$aGastrointestinal Microbiome
000304497 650_7 $$2Other$$aHepatobiliary tumours
000304497 650_7 $$2Other$$aIMMUNOLOGY
000304497 650_7 $$2Other$$aMicrobiota
000304497 650_7 $$052CMI0WC3Y$$2NLM Chemicals$$aatezolizumab
000304497 650_7 $$02S9ZZM9Q9V$$2NLM Chemicals$$aBevacizumab
000304497 650_7 $$2NLM Chemicals$$aAntibodies, Monoclonal, Humanized
000304497 650_7 $$2NLM Chemicals$$aImmune Checkpoint Inhibitors
000304497 650_2 $$2MeSH$$aHumans
000304497 650_2 $$2MeSH$$aLiver Neoplasms: therapy
000304497 650_2 $$2MeSH$$aLiver Neoplasms: drug therapy
000304497 650_2 $$2MeSH$$aBevacizumab: therapeutic use
000304497 650_2 $$2MeSH$$aDouble-Blind Method
000304497 650_2 $$2MeSH$$aFecal Microbiota Transplantation: methods
000304497 650_2 $$2MeSH$$aAntibodies, Monoclonal, Humanized: therapeutic use
000304497 650_2 $$2MeSH$$aCarcinoma, Hepatocellular: therapy
000304497 650_2 $$2MeSH$$aCarcinoma, Hepatocellular: drug therapy
000304497 650_2 $$2MeSH$$aDrug Resistance, Neoplasm
000304497 650_2 $$2MeSH$$aClinical Trials, Phase II as Topic
000304497 650_2 $$2MeSH$$aRandomized Controlled Trials as Topic
000304497 650_2 $$2MeSH$$aMulticenter Studies as Topic
000304497 650_2 $$2MeSH$$aImmune Checkpoint Inhibitors: therapeutic use
000304497 650_2 $$2MeSH$$aGastrointestinal Microbiome
000304497 650_2 $$2MeSH$$aAntineoplastic Combined Chemotherapy Protocols: therapeutic use
000304497 7001_ $$0P:(DE-He78)72e6f8462f1b903eef99df71d9d8817b$$aRoberti, Maria Paula$$b1$$udkfz
000304497 7001_ $$aVehreschild, Maria Jgt$$b2
000304497 7001_ $$aTsakmaklis, Anastasia$$b3
000304497 7001_ $$aSpringfeld, Christoph$$b4
000304497 7001_ $$aTeufel, Andreas$$b5
000304497 7001_ $$aEttrich, Thomas$$b6
000304497 7001_ $$aJochheim, Leonie$$b7
000304497 7001_ $$aKandulski, Arne$$b8
000304497 7001_ $$aMissios, Pavlos$$b9
000304497 7001_ $$aMohr, Raphael$$b10
000304497 7001_ $$aReichart, Alexander$$b11
000304497 7001_ $$aWaldschmidt, Dirk T$$b12
000304497 7001_ $$aSauer, Lukas D$$b13
000304497 7001_ $$aSander, Anja$$b14
000304497 7001_ $$aSchirmacher, Peter$$b15
000304497 7001_ $$0P:(DE-He78)ed0321409c9cde20b380ae663dbcefd1$$aJäger, Dirk$$b16$$udkfz
000304497 7001_ $$aMichl, Patrick$$b17
000304497 7001_ $$0P:(DE-He78)54a6641a6c26ddc49cc754740e90b438$$aDill, Michael$$b18$$eLast author$$udkfz
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