000285125 001__ 285125 000285125 005__ 20240229155104.0 000285125 0247_ $$2doi$$a10.1111/cts.13661 000285125 0247_ $$2pmid$$apmid:37920921 000285125 0247_ $$2ISSN$$a1752-8054 000285125 0247_ $$2ISSN$$a1752-8062 000285125 037__ $$aDKFZ-2023-02249 000285125 041__ $$aEnglish 000285125 082__ $$a610 000285125 1001_ $$00000-0001-8036-8806$$aHohmann, Nicolas$$b0 000285125 245__ $$aProtocol of the IntenSify-Trial: An open-label phase I trial of the CYP3A inhibitor cobicistat and the cytostatics gemcitabine and nab-paclitaxel in patients with advanced stage or metastatic pancreatic ductal adenocarcinoma to evaluate the combination's pharmacokinetics, safety, and efficacy. 000285125 260__ $$aOxford$$bBlackwell [[-2008]]$$c2023 000285125 3367_ $$2DRIVER$$aarticle 000285125 3367_ $$2DataCite$$aOutput Types/Journal article 000285125 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1703859399_31546 000285125 3367_ $$2BibTeX$$aARTICLE 000285125 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000285125 3367_ $$00$$2EndNote$$aJournal Article 000285125 500__ $$aClinical Trial / #EA:A010#LA:A010# / 2023 Dec;16(12):2483-2493 000285125 520__ $$aExpression of CYP3A5 protein is a basal and acquired resistance mechanism of pancreatic ductal adenocarcinoma cells conferring protection against the CYP3A and CYP2C8 substrate paclitaxel through metabolic degradation. Inhibition of CYP3A isozymes restores the cells sensitivity to paclitaxel. The combination of gemcitabine and nab-paclitaxel is an established regimen for the treatment of metastasized or locally advanced inoperable pancreatic cancer. Cobicistat is a CYP3A inhibitor developed for the pharmacoenhancement of protease inhibitors. The addition of cobicistat to gemcitabine and nab-paclitaxel may increase the antitumor effect. We will conduct a phase I dose escalation trial with a classical 3 + 3 design to investigate the safety, tolerability, and pharmacokinetics (PKs) of gemcitabine, nab-paclitaxel, and cobicistat. Although the doses of gemcitabine (1000 mg/m2 ) and cobicistat (150 mg) are fixed, three dose levels of nab-paclitaxel (75, 100, and 125 mg/m2 ) will be explored to account for a potential PK drug interaction. After the dose escalation phase, we will set the recommended dose for expansion (RDE) and treat up to nine patients in an expansion part of the trial. The trial is registered under the following identifiers EudraCT-Nr. 2019-001439-29, drks.de: DRKS00029409, and ct.gov: NCT05494866. Overcoming resistance to paclitaxel by CYP3A5 inhibition may lead to an increased efficacy of the gemcitabine and nab-paclitaxel regimen. Safety, efficacy, PK, and RDE data need to be acquired before investigating this combination in a large-scale clinical study. 000285125 536__ $$0G:(DE-HGF)POF4-311$$a311 - Zellbiologie und Tumorbiologie (POF4-311)$$cPOF4-311$$fPOF IV$$x0 000285125 588__ $$aDataset connected to CrossRef, PubMed, , Journals: inrepo02.dkfz.de 000285125 7001_ $$0P:(DE-He78)0f44fcb0b05507b0a20b175f7ba9ed1c$$aSprick, Martin$$b1$$eFirst author 000285125 7001_ $$aAhmed, Azaz$$b2 000285125 7001_ $$00000-0002-2190-1698$$aBurhenne, Jürgen$$b3 000285125 7001_ $$00000-0003-0294-2483$$aKirchner, Marietta$$b4 000285125 7001_ $$0P:(DE-He78)a49833282b3e64d27fb1d08ceb6b2538$$aLe Cornet, Lucian$$b5$$udkfz 000285125 7001_ $$0P:(DE-He78)ad1537a0b564af5f6cd80581a08a0788$$aKratzmann, Markus$$b6$$udkfz 000285125 7001_ $$aHajda, Jacek$$b7 000285125 7001_ $$00000-0003-1001-103X$$aStenzinger, Albrecht$$b8 000285125 7001_ $$0P:(DE-He78)a0c2037d9054be26907a05ae520d5756$$aSteindorf, Karen$$b9 000285125 7001_ 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