A phase 2, randomized, double-blind, placebo-controlled trial of clinical activity and safety of subcutaneous Å6 in women with asymptomatic CA125 progression after first-line chemotherapy of epithelial ovarian cancer

Objectives: Å6 is a novel peptide that interferes with single-chain urokinase plasminogen activator activity and has shown anti-angiogenic, anti-migratory, and anti-invasive properties. We evaluated clinical efficacy and safety of subcutaneously administered Å6 in women with epithelial ovarian cancer. Methods: Women with epithelial ovarian, fallopian tube, or primary peritoneal cancer in clinical remission after first-line chemotherapy with 2 consecutive increases of CA125 values above normal but with no disease on physical examination or imaging studies were randomly assigned to receive daily subcutaneous injections of placebo, low-dose Å6 (150 mg), or high-dose Å6 (300 mg) until disease progression or end of study participation. Primary endpoints were time to clinical progression of disease and safety of Å6. Secondary endpoints were changes in serum CA125 and biomarkers of the urokinase system. Results: Data are available for 24 women (placebo, n = 12; low-dose, n = 8; high-dose n = 4). Å6 therapy was associated with a statistically significant delay in time to clinical progression (log-rank p-value 0.01) with a median of 100 days (95% CI: 64,168) for women who received Å6 compared with 49 days (95% CI: 29,67) for women who received placebo. The treatments appeared to be well tolerated. Treatment was not associated with CA125 response (p = 0.44). On-treatment values for plasma urokinase plasminogen activator receptor were statistically significantly lower in the Å6 groups compared with placebo (p = 0.02). Conclusions: Å6 therapy increases time to clinical disease progression and appears to be well tolerated in this patient population.