A phase II study of a urokinase-derived peptide (A6) in the treatment of persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma: a Gynecologic Oncology Group study

Gynecol Oncol. 2012 Jun;125(3):635-9. doi: 10.1016/j.ygyno.2012.03.023. Epub 2012 Mar 22.

Abstract

Purpose: This multi-institutional phase II trial assessed the activity and tolerability of the anti-metastatic A6 peptide that binds CD44 in patients with persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma (EOC/FTC/PPC).

Patients and methods: Women with persistent or recurrent EOC/FTC/PPC were eligible for participation if they had measurable disease defined by RECIST criteria, good performance status, and good overall organ function. Patients must have received one prior platinum-based chemotherapeutic regimen and were allowed to have received one additional cytotoxic regimen for the management of recurrent or persistent disease. Women received a 150 mg twice daily subcutaneous dose of A6 and continued on treatment until disease progression or unacceptable toxicity. Primary measures of clinical efficacy were objective tumor response and progression-free survival (PFS) at 6 months. The association of CD44 in archival tissue specimens with clinical outcome was investigated.

Results: Thirty-one eligible patients were evaluated. No responses were observed. Two patients (6.5%) were progression free for at least 6 months. The median PFS was 2.0 months, and median overall survival has not yet been reached. One patient died of hemorrhage which was possibly study related. There were no grade 4 toxicities. The most common grade 3 toxicities were constitutional (2/31; 6.5%). Archival specimens were available for 27 patients, and 5 (18.5%) were CD44 positive by immunohistochemistry. CD44 expression was not associated with the 6-month PFS (p=0.342).

Conclusion: A6 was well tolerated but had minimal activity in patients with persistent or recurrent EOC/FTC/PPC.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Ovarian Epithelial
  • Disease-Free Survival
  • Fallopian Tube Neoplasms / drug therapy*
  • Fallopian Tube Neoplasms / metabolism
  • Female
  • Humans
  • Hyaluronan Receptors / biosynthesis
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasms, Glandular and Epithelial / drug therapy*
  • Neoplasms, Glandular and Epithelial / metabolism
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / metabolism
  • Peptide Fragments / adverse effects
  • Peptide Fragments / therapeutic use*
  • Peritoneal Neoplasms / drug therapy*
  • Peritoneal Neoplasms / metabolism
  • Urokinase-Type Plasminogen Activator / adverse effects
  • Urokinase-Type Plasminogen Activator / therapeutic use*

Substances

  • CD44 protein, human
  • Hyaluronan Receptors
  • Peptide Fragments
  • Urokinase-Type Plasminogen Activator
  • acetyl-lysyl-prolyl-seryl-seryl-prolyl-prolyl-glutamyl-glutamic acid amide