Phase I/II marker lesion study of intravesical BC-819 DNA plasmid in H19 over expressing superficial bladder cancer refractory to bacillus Calmette-Guerin

J Urol. 2008 Dec;180(6):2379-83. doi: 10.1016/j.juro.2008.08.006. Epub 2008 Oct 31.


Purpose: We studied the safety and preliminary efficacy (marker tumor ablation) of 5 doses of BC-819 given as 6 intravesical infusions in patients with superficial bladder cancer in whom intravesical therapy with bacillus Calmette-Guerin had failed. BC-819 is a DNA plasmid that contains H19 gene regulatory sequences that drive the expression of an intracellular toxin.

Materials and methods: A total of 18 patients in 4 groups of 3 and 1 group of 6 received escalating doses of BC-819 intravesically during 7 weeks. Patients had low grade superficial bladder cancer, which expressed H19. The effect on a marker tumor was examined 12 weeks after starting treatment. The escalating doses were 2, 4, 6, 12 and 20 mg plasmid per intravesical treatment. Responders continued to receive BC-819 once monthly every month for 1 year.

Results: No dose limiting toxicity was observed. The most frequent adverse events were mild to moderate bladder discomfort, dysuria, micturition urgency, urinary tract infection, diarrhea, hypertension and asthenia. Intravesical administration of BC-819 resulted in complete ablation of the marker tumor without any new tumors in 4 of the 18 patients for a 22% overall complete response rate. Eight of the 18 patients (44%) had complete marker tumor ablation or a 50% reduction of the marker lesion. Nine patients received monthly maintenance, of whom 4 and 1 were disease-free at 35 and 49 weeks, respectively.

Conclusions: Intravesical BC-819 causes tumor ablation following intravesical administration at doses that were well tolerated. It is worthy of continued clinical investigation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / therapeutic use
  • Administration, Intravesical
  • Aged
  • Aged, 80 and over
  • BCG Vaccine / therapeutic use
  • DNA / administration & dosage*
  • Dose-Response Relationship, Drug
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Middle Aged
  • Plasmids*
  • RNA, Long Noncoding
  • RNA, Untranslated / biosynthesis
  • Treatment Outcome
  • Urinary Bladder Neoplasms / drug therapy*
  • Urinary Bladder Neoplasms / genetics


  • Adjuvants, Immunologic
  • BCG Vaccine
  • H19 long non-coding RNA
  • RNA, Long Noncoding
  • RNA, Untranslated
  • DNA