Investigational New Drugs

, Volume 29, Issue 6, pp 1465–1474

A phase II study of 2-methoxyestradiol (2ME2) NanoCrystal® dispersion (NCD) in patients with taxane-refractory, metastatic castrate-resistant prostate cancer (CRPC)

  • Michael R. Harrison
  • Noah M. Hahn
  • Roberto Pili
  • William K. Oh
  • Hans Hammers
  • Christopher Sweeney
  • KyungMann Kim
  • Scott Perlman
  • Jamie Arnott
  • Carolyn Sidor
  • George Wilding
  • Glenn Liu
PHASE II STUDIES

DOI: 10.1007/s10637-010-9455-x

Cite this article as:
Harrison, M.R., Hahn, N.M., Pili, R. et al. Invest New Drugs (2011) 29: 1465. doi:10.1007/s10637-010-9455-x

Summary

Purpose: 2ME2 (Panzem®) is a non-estrogenic derivative of estradiol with antiproliferative and antiangiogenic activity. Preclinical data support antitumor activity in prostate cancer. This trial evaluated the efficacy of 2ME2 NCD in patients with taxane-refractory, metastatic CRPC. Experimental Design: Patients with metastatic CRPC who had progressed on only one prior taxane-based regimen were eligible. All patients received 2ME2 NCD at 1,500 mg orally four times daily, repeated in 28 day cycles. The primary endpoint was progression-free survival at month 6, with a secondary endpoint of PSA response. An exploratory endpoint was metabolic response on FDG-PET imaging. Results: A total of 50 pts was planned. The study was terminated after 21 pts when a futility analysis showed the primary endpoint was unlikely to be reached. The median number of cycles on study was 2 (range <1 to 12). Adverse events (AE) of grade ≥3 related to the study drug occurred in 7 unique patients (33%): elevations in liver function tests, fatigue or weakness, gastrointestinal hemorrhage, and hyponatremia. Paired FDG-PET scans were obtained for 11 pts. No metabolic responses were observed. Conclusions: 2ME2 NCD did not appear to have clinically significant activity in this study. 2ME2 NCD was well-tolerated and showed some evidence of biologic activity. Given the aggressive biology in this taxane-refractory population, the potential benefit from a cytostatic agent like 2ME2 might better be realized in the pre-chemotherapy (or rising PSA only) stage of CRPC.

Keywords

Prostate cancer Castrate-resistant Antiangiogenesis Antiproliferative PET scan Clinical trials 

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Michael R. Harrison
    • 1
    • 9
    • 10
  • Noah M. Hahn
    • 2
  • Roberto Pili
    • 3
  • William K. Oh
    • 4
  • Hans Hammers
    • 5
    • 10
  • Christopher Sweeney
    • 6
    • 10
  • KyungMann Kim
    • 7
    • 10
  • Scott Perlman
    • 7
    • 9
  • Jamie Arnott
    • 8
  • Carolyn Sidor
    • 8
  • George Wilding
    • 7
    • 10
  • Glenn Liu
    • 7
    • 9
    • 10
  1. 1.University of Wisconsin Carbone Cancer CenterMadisonUSA
  2. 2.Indiana University Simon Cancer CenterIndianapolisUSA
  3. 3.Roswell Park Cancer InstituteBuffaloUSA
  4. 4.Mount Sinai Medical CenterTisch Cancer InstituteNew YorkUSA
  5. 5.Johns Hopkins Kimmel Cancer CenterBaltimoreUSA
  6. 6.Dana-Farber Cancer InstituteBostonUSA
  7. 7.University of Wisconsin Carbone Cancer CenterMadisonUSA
  8. 8.EntreMed, Inc.RockvilleUSA
  9. 9.University of Wisconsin Translational Imaging Research (TIR) GroupMadisonUSA
  10. 10.Department of Defense Prostate Cancer Clinical Trials ConsortiumNew YorkUSA