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

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.