A phase II randomized, double-blind, placebo-controlled trial of clinical activity and safety of Å6 in patients with asymptomatic CA 125 progression of epithelial ovarian, fallopian tube, or primary peritoneal cancer

Abstract

16014 Background: Patients (pts) with epithelial ovarian cancer (EOC) often relapse and rising CA 125 levels predate clinical or radiological appearance of tumor. High tumor and serum levels of urokinase plasminogen activator (uPA) in EOC correlate to adverse outcomes. Å6 is a novel peptide derived from human uPA that down-regulates the uPA system and has anti-angiogenic and anti-metastatic activity in animals. Methods: Pts with EOC, fallopian tube, or primary peritoneal cancer in clinical remission after first line chemotherapy had to have 2 consecutive rises of CA 125 levels above normal with no disease on physical examination or imaging studies. Pts were randomized to receive daily subcutaneous injections of placebo, 150 mg Å6, or 300 mg Å6 until disease progression. The primary objectives were to assess safety and clinical activity of Å6 by the effect on the onset of disease progression. Results: 48 pts were planned for the study. The trial ended early with 24 patients {12 pts (50%) placebo, 8 pts (33%) low dose Å6, 4 pts (17%) high dose Å6} randomized, treated and followed for up to 9 months. Despite early study termination and small sample size, A6 therapy was associated with a statistically significant progression free survival (PFS) (log rank p value=0.01) with a median PFS of 100 days (95% CI 64,168) compared to 49 days (95% CI 29,67) in pts who received the placebo. The treatments were well tolerated with one serious adverse event (transient nausea and dyspnea ) possibly related to study drug. Treatment was not associated with CA 125 response (Fisher exact test p value= 0.44). Conclusions: Å6 therapy increases PFS of patients with EOC and asymptomatic progression of CA 125. This therapy is novel, safe, feasible and deserves further investigation [Table: see text]