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@ARTICLE{Hohmann:285125,
      author       = {N. Hohmann and M. Sprick$^*$ and A. Ahmed and J. Burhenne
                      and M. Kirchner and L. Le Cornet$^*$ and M. Kratzmann$^*$
                      and J. Hajda and A. Stenzinger and K. Steindorf$^*$ and S.
                      Delorme$^*$ and H.-P. Schlemmer$^*$ and S. Riethdorf and R.
                      van Schaik and K. Pantel and J. Siveke$^*$ and T.
                      Seufferlein and D. Jäger$^*$ and W. E. Haefeli and A.
                      Trumpp$^*$ and C. Springfeld},
      title        = {{P}rotocol of the {I}nten{S}ify-{T}rial: {A}n open-label
                      phase {I} trial of the {CYP}3{A} 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.},
      journal      = {Clinical and translational science},
      volume       = {16},
      number       = {12},
      issn         = {1752-8054},
      address      = {Oxford},
      publisher    = {Blackwell [[-2008]]},
      reportid     = {DKFZ-2023-02249},
      pages        = {2483-2493},
      year         = {2023},
      note         = {Clinical Trial / #EA:A010#LA:A010# / 2023
                      Dec;16(12):2483-2493},
      abstract     = {Expression 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.},
      cin          = {A010 / W010 / C110 / E010 / ED01 / D120 / HD01},
      ddc          = {610},
      cid          = {I:(DE-He78)A010-20160331 / I:(DE-He78)W010-20160331 /
                      I:(DE-He78)C110-20160331 / I:(DE-He78)E010-20160331 /
                      I:(DE-He78)ED01-20160331 / I:(DE-He78)D120-20160331 /
                      I:(DE-He78)HD01-20160331},
      pnm          = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
      pid          = {G:(DE-HGF)POF4-311},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37920921},
      doi          = {10.1111/cts.13661},
      url          = {https://inrepo02.dkfz.de/record/285125},
}