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Investigational New Drugs

, Volume 34, Issue 1, pp 75–83 | Cite as

Phase I, dose-escalating study of elisidepsin (Irvalec®), a plasma membrane-disrupting marine antitumor agent, in combination with erlotinib in patients with advanced malignant solid tumors

  • Sanjay Goel
  • Santiago Viteri
  • Teresa Morán
  • Cinthya Coronado
  • Jorge Luis Iglesias Dios
  • Bernardo Miguel-Lillo
  • Eva M. Fernández-García
  • Rafael Rosell
PHASE I STUDIES

Summary

Objective To determine the recommended dose for phase II trials of elisidepsin (PM02734, Irvalec®) in combination with erlotinib in patients with advanced malignant solid tumors. Methods Open-label, dose-escalating, phase I study of intravenous elisidepsin administered weekly (days 1, 8 and 15) over 3 h as a flat dose (FD) and daily oral erlotinib, every 3 weeks. A pharmacokinetic analysis was done on blood samples collected around the first elisidepsin infusion. Results Thirty patients were treated across six different dose levels (DLs) ranging from elisidepsin 0.33–2.25 mg/erlotinib 100–150 mg. Two patients had dose-limiting toxicities: grade 3 bilirubin increase (DL3: 0.75 mg/150 mg) and a dose omission for > 2 weeks due to grade 3 alanine aminotransferase increase (DL6: 2.25 mg/100 mg). The daily erlotinib dose was escalated to 150 mg at DL2-DL5, but decreased to 100 mg at DL6, as most grade 3 toxicities were related to this agent only. The most frequent toxicities were transaminase increases (related to elisidepsin), and rash, pruritus and diarrhea (related to erlotinib). No objective responses were observed. Despite no overlapping toxicities, the combination was declared unfeasible due to frequent elisidepsin dose delays. The pharmacokinetics of elisidepsin/erlotinib was not significantly different from that of each agent alone. Conclusion The difficulty in combining elisidepsin with the standard dose of erlotinib (150 mg), together with the lack of antitumor activity, made the combination unattractive for further development. The trial was closed without having determined a recommended dose.

Keywords

PM02734 Phase I Erlotinib Combination Dose-limiting toxicities 

Notes

Acknowledgments

We thank all the staff who contributed to the care of the patients included in this study.

Compliance with ethical standards

Conflict of interest

Cinthya Coronado, Eva M. Fernández-García, Jorge Luis Iglesias Dios and Bernardo Miguel-Lillo are employees of Pharma Mar.

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Sanjay Goel
    • 1
  • Santiago Viteri
    • 2
  • Teresa Morán
    • 3
  • Cinthya Coronado
    • 4
  • Jorge Luis Iglesias Dios
    • 4
  • Bernardo Miguel-Lillo
    • 4
  • Eva M. Fernández-García
    • 4
  • Rafael Rosell
    • 3
  1. 1.Montefiore Medical CenterBronxUSA
  2. 2.Instituto Universitario DexeusBarcelonaSpain
  3. 3.Catalan Institute of OncologyHospital Germans Trias I PujolBadalonaSpain
  4. 4.Pharma Mar, S.A.MadridSpain

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