Investigational New Drugs

, Volume 28, Issue 5, pp 670–676

Phase II study of darinaparsin in patients with advanced hepatocellular carcinoma

  • Jennifer Wu
  • Charles Henderson
  • Lynn Feun
  • Peter Van Veldhuizen
  • Philip Gold
  • Hui Zheng
  • Theresa Ryan
  • Lawrence S. Blaszkowsky
  • HaoBin Chen
  • Max Costa
  • Barry Rosenzweig
  • MaryLynn Nierodzik
  • Howard Hochster
  • Franco Muggia
  • Giovanni Abbadessa
  • Jonathan Lewis
  • Andrew X. Zhu
PHASE II STUDIES

DOI: 10.1007/s10637-009-9286-9

Cite this article as:
Wu, J., Henderson, C., Feun, L. et al. Invest New Drugs (2010) 28: 670. doi:10.1007/s10637-009-9286-9

Summary

Background Darinaparsin is a novel organic arsenic that reaches higher intracellular concentration with decreased toxicity compared to inorganic arsenic. We conducted a multi-center phase II study with darinaparsin in patients with advanced HCC. Methods Eligibility criteria included unresectable or metastatic measurable HCC, up to two prior systemic treatments, ECOG performance status ≤2, Child Pugh Class A or B and adequate organ functions. Darinaparsin was administered at 420 mg/m2 intravenously, twice weekly at least 72 h apart for 3 weeks in a 4-week cycle. The primary end point was response rate. A Simon two-stage design was used. Results Among 15 patients in the first stage, no objective responses were observed. Two patients had stable disease. The median number of cycles on study per patient was 2 (1–6). The median progression free survival and overall survival were 55 days (95% confidence interval: 50–59) and 190 days (95% confidence interval: 93–227), respectively. No treatment related hospitalizations or deaths occurred. Treatment related grade 1–2 toxicities included nausea, vomiting (26.7% each), fatigue (20%), anorexia and diarrhea (13.3% each). Grade 3 anorexia, wheezing, agitation, abdominal pain and SGPT were observed in 1 patient each (6.7%). One patient experienced grade 4 hypoglycemia (6.7%). Conclusions Darinaparsin could be safely administered with tolerable toxicity profiles, and no QTc prolongation in patients with advanced HCC. However, at this dose and schedule, it has shown no objective responses in HCC and this trial was terminated as planned after the first stage of efficacy analysis.

Keywords

Darinaparsin Hepatocellular carcinoma Clinical trials Phase II study 

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Jennifer Wu
    • 1
    • 12
  • Charles Henderson
    • 2
  • Lynn Feun
    • 3
  • Peter Van Veldhuizen
    • 4
  • Philip Gold
    • 5
  • Hui Zheng
    • 7
  • Theresa Ryan
    • 1
  • Lawrence S. Blaszkowsky
    • 8
  • HaoBin Chen
    • 9
  • Max Costa
    • 9
  • Barry Rosenzweig
    • 10
  • MaryLynn Nierodzik
    • 11
  • Howard Hochster
    • 1
  • Franco Muggia
    • 1
  • Giovanni Abbadessa
    • 6
  • Jonathan Lewis
    • 6
  • Andrew X. Zhu
    • 8
  1. 1.Department of Medical OncologyNYU School of MedicineNew YorkUSA
  2. 2.Department of Medical OncologyPiedmont Hospital Research InstituteAtlantaUSA
  3. 3.Department of Medical OncologyUniversity of Miami Hospital and ClinicsMiamiUSA
  4. 4.Department of Hematology and Medical OncologyKansas City Veterans Administration Medical CenterKansasUSA
  5. 5.Department of Medical OncologySwedish Cancer Institute ResearchSeattleUSA
  6. 6.ResearchZiopharm Oncology Inc.BostonUSA
  7. 7.Department of BiostatisticsMassachusetts General HospitalBostonUSA
  8. 8.Department of Medical OncologyMassachusetts General HospitalBostonUSA
  9. 9.Department of Environmental MedicineNYU School of MedicineNew YorkUSA
  10. 10.Department of CardiologyNYU School of MedicineNew YorkUSA
  11. 11.Department of Hematology and Medical OncologyNYU School of MedicineNew YorkUSA
  12. 12.NYU Cancer InstituteNew YorkUSA

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