Phase I/II Marker Lesion Study of Intravesical BC-819 DNA Plasmid in H19 Over Expressing Superficial Bladder Cancer Refractory to Bacillus Calmette-Guerin

Abraham Ami Sidi, Patricia Ohana, Shalva Benjamin, Moshe Shalev, Janet H. Ransom, Donald Lamm, Avraham Hochberg, Ilan Leibovitch

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)2379-2383
Number of pages5
JournalJournal of Urology
Volume180
Issue number6
DOIs
StatePublished - Dec 2008
Externally publishedYes

Keywords

  • diphtheria toxin
  • dose-response relationship
  • drug
  • plasmids
  • toxicity
  • urinary bladder neoplasms

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