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Investigational New Drugs

, Volume 32, Issue 1, pp 171–177 | Cite as

A Phase II multicenter, open-label, clinical and pharmokinetic trial of PM00104 in patients with advanced Ewing Family of Tumors

  • Robin L. JonesEmail author
  • Stefano Ferrari
  • Jean Yves Blay
  • Fariba Navid
  • Pilar Lardelli
  • Vicente Alfaro
  • Mariano Siguero
  • Neelesh Soman
  • Sant P. Chawla
PHASE II STUDIES

Summary

Ewing sarcoma is a rare connective tissue tumor characterized by the translocation of the EWS gene, mainly between chromosome 11 and 22, giving rise to gene re-arrangements between the EWS gene and various members of the ETS gene family. Multi-agent chemotherapy has improved the outcome for patients with localized Ewing sarcoma, but survival of patients with recurrent/metastatic disease remains poor. An exploratory two-stage, single-arm Phase II multicenter trial of the synthetic alkaloid, PM00104, was conducted in patients with recurrent Ewing sarcoma. The primary end point of the trial was objective response rate. PM00104 was administered at a dose of 2 mg/m2 on Days 1, 8 and 15 of a 4 week cycle. Seventeen patients were recruited. No objective responses were reported in the 16 patients evaluable for efficacy. Recruitment was closed without proceeding to the second stage of the trial. Four patients achieved stable disease as best response, and in two of these patients the stabilization was longer than 4 months. The median progression-free survival was 1.8 months (95 % CI, 0.9–3.5 months) and median overall survival was not reached (95%CI, 56.2 % at censored data). Pharmacokinetics in patients with Ewing sarcoma was similar to that previously reported in other patient populations. PM00104 showed modest activity in Ewing sarcoma at 2 mg/m2 on a weekly schedule. There remains an unmet need for effective therapies for patients with advanced/metastatic Ewing sarcoma.

Keywords

PM00104 Ewing sarcoma Metastatic disease Safety 

Notes

Conflict of interest

Pilar Lardelli, Vicente Alfaro and Mariano Siguero are employed by Pharmamar. All other authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Robin L. Jones
    • 1
    Email author
  • Stefano Ferrari
    • 2
  • Jean Yves Blay
    • 3
  • Fariba Navid
    • 4
  • Pilar Lardelli
    • 5
  • Vicente Alfaro
    • 5
  • Mariano Siguero
    • 5
  • Neelesh Soman
    • 6
  • Sant P. Chawla
    • 6
  1. 1.University of Washington/Fred Hutchinson Cancer Research CenterSeattleUSA
  2. 2.Instituto Ortopedico RizzoliBolognaItaly
  3. 3.Centre Léon BéradLyonFrance
  4. 4.Department of OncologySt. Jude Children’s Research HospitalMemphisUSA
  5. 5.PharmaMar S.A., Colmenar ViejoMadridSpain
  6. 6.Sarcoma Oncology CenterSanta MonicaUSA

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