Phase II evaluation of dasatinib in the treatment of recurrent or persistent epithelial ovarian or primary peritoneal carcinoma: a Gynecologic Oncology Group study

Gynecol Oncol. 2012 Oct;127(1):70-4. doi: 10.1016/j.ygyno.2012.06.009. Epub 2012 Jun 16.

Abstract

Objectives: Preclinical data suggest an important role for the sarcoma proto-oncogene tyrosine kinase (SRC) in the oncogenesis of epithelial ovarian cancer (EOC) or primary peritoneal carcinoma (PPC). The Gynecologic Oncology Group (GOG) conducted a Phase II trial to evaluate the efficacy and safety of dasatinib, an oral SRC-family inhibitor in EOC/PPC, and explored biomarkers for possible association with clinical outcome.

Methods: Eligible women had measurable, recurrent or persistent EOC/PPC and had received one or two prior regimens which must have contained a platinum and a taxane. Patients were treated with 100mg orally daily of dasatinib continuously until progression of disease or adverse effects prevented further treatment. Primary endpoints were progression-free survival (PFS)≥6months and response rate. Serial plasma samples were assayed for multiple biomarkers. Circulating free DNA was quantified as were circulating tumor and endothelial cells.

Results: Thirty-five (35) patients were enrolled in a two-stage sequential design. Of the 34 eligible and evaluable patients, 20.6% (90% confidence interval: 10.1%, 35.2%) had a PFS≥6months; there were no objective responses. Grade 3-4 toxicities were gastrointestinal (mostly nausea and emesis; n=4), pulmonary (dyspnea and/or pleural effusion; n=4) and pain (n=5), and infrequent instances of anemia, malaise, insomnia, rash, and central nervous system hemorrhage. Lack of clinical activity limited any correlation of biomarkers with outcome.

Conclusion: Dasatinib has minimal activity as a single-agent in patients with recurrent EOC/PPC.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Ovarian Epithelial
  • Dasatinib
  • Disease-Free Survival
  • Female
  • Humans
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Neoplasms, Glandular and Epithelial / drug therapy*
  • Ovarian Neoplasms / drug therapy*
  • Peritoneal Neoplasms / drug therapy*
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyrimidines / adverse effects
  • Pyrimidines / therapeutic use*
  • Thiazoles / adverse effects
  • Thiazoles / therapeutic use*

Substances

  • Protein Kinase Inhibitors
  • Pyrimidines
  • Thiazoles
  • Dasatinib