Investigational New Drugs

, Volume 30, Issue 2, pp 794–802

A phase II study of 2-methoxyestradiol nanocrystal colloidal dispersion alone and in combination with sunitinib malate in patients with metastatic renal cell carcinoma progressing on sunitinib malate

Authors

    • Section of Hematology/OncologyUniversity of Wisconsin Carbone Cancer Center, Wisconsin Institutes for Medical Research
  • Jens Eickhoff
    • University of Wisconsin Carbone Cancer Center
  • Roberto Pili
    • Roswell Park Cancer Institute
  • Theodore Logan
    • Indiana University Simon Cancer Center
  • Michael Carducci
    • Sidney Kimmel Comprehensive Cancer Center
  • Jamie Arnott
    • EntreMed, Inc., Research Triangle Park Center
  • Anthony Treston
    • EntreMed, Inc.
  • George Wilding
    • University of Wisconsin Carbone Cancer Center, Wisconsin Institutes for Medical Research
  • Glenn Liu
    • University of Wisconsin Carbone Cancer Center, Wisconsin Institutes for Medical Research
PHASE II STUDIES

DOI: 10.1007/s10637-010-9618-9

Cite this article as:
Bruce, J.Y., Eickhoff, J., Pili, R. et al. Invest New Drugs (2012) 30: 794. doi:10.1007/s10637-010-9618-9

Summary

Background Current treatment for metastatic renal cell cancer with vascular endothelial growth factor (VEGF) tyrosine kinase inhibitors (TKI) have provided improved overall survival, but complete responses are rare. We conducted a multicenter phase II study to evaluate the objective response rate of 2-methoxyestradiol (2ME2 NCD) alone and in combination with sunitinib for patients with metastatic renal cell carcinoma who have progressed on sunitinib alone. Methods Adults with metastatic kidney cancer were stratified depending on whether they were still taking sunitinib or had discontinued sunitinib therapy at the time of registration. Patients were treated with 2ME2 NCD alone or in combination with sunitinib. The primary endpoint was objective response rate. Results In total, 17 patients were enrolled, and 12 were evaluable for response (arm A, n = 7; arm b, n = 5). In arm A, four patients had the best response of stable disease, and three patients developed disease progression. In arm B, three patients had a best response of stable disease, and two patients had disease progression. One patient continued to receive treatment for a total of 14 cycles before developing disease progression. Fatigue was the most common observed toxicities. Thirty five percent of patients required discontinuation of therapy secondary to toxicities. Conclusions 2ME2 NCD had minimal anti-tumor activity, with no observed objective responses. The study was terminated because 2ME2 NCD was not found to be tolerable at the recommended phase 2 dose in this patient population. A newer 2ME2 analog is in development with a more favorable toxicity profile and increased potency.

Keywords

Renal cell carcinomaClinical trialsPhase II2-methoxyestradiolSunitinib malateAntiangiogenic agent

Copyright information

© Springer Science+Business Media, LLC 2010