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

Abstract

PurposeThis 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 methodsWomen 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 150mg 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 6months. The association of CD44 in archival tissue specimens with clinical outcome was investigated. ResultsThirty-one eligible patients were evaluated. No responses were observed. Two patients (6.5%) were progression free for at least 6months. The median PFS was 2.0months, 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). ConclusionA6 was well tolerated but had minimal activity in patients with persistent or recurrent EOC/FTC/PPC.