title: A phase 2, randomized, double-blind, placebo-controlled trial of clinical activity and safety of subcutaneous A6 in women with asymptomatic CA125 progression after first-line chemotherapy of epithelial ovarian cancer.
abstract: OBJECTIVE
  A6 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 A6 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 A6 (150 mg), or high-dose A6 (300 mg) until disease progression or end of study participation. Primary endpoints were time to clinical progression of disease and safety of A6. 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). A6 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 A6 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 A6 groups compared with placebo (p=0.02).
  
  
  CONCLUSIONS
  A6 therapy increases time to clinical disease progression and appears to be well tolerated in this patient population.
authors.affiliation: Division of Gynecologic Oncology, Medical College of Georgia, Augusta, GA, USA. sghamande@mail.mcg.edu
authors.forename: Sharad A
authors.initials: SA
authors.lastname: Ghamande
authors.forename: Michael H
authors.initials: MH
authors.lastname: Silverman
authors.forename: Warner
authors.initials: W
authors.lastname: Huh
authors.forename: Kian
authors.initials: K
authors.lastname: Behbakht
authors.forename: Greg
authors.initials: G
authors.lastname: Ball
authors.forename: Luceli
authors.initials: L
authors.lastname: Cuasay
authors.forename: Sidse O
authors.initials: SO
authors.lastname: Würtz
authors.forename: Nils
authors.initials: N
authors.lastname: Brunner
authors.forename: Michael A
authors.initials: MA
authors.lastname: Gold