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

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.

• Authors: Abraham Ami Sidi, Patricia Ohana, Shalva Benjamin, Moshe Shalev, Janet H Ransom, Donald Lamm, Avraham Hochberg, Ilan Leibovitch
• Journal: The Journal of urology (J Urol) Vol. 180 Issue 6 Pg. 2379-83 (Dec 2008) ISSN: 1527-3792 [Electronic] United States
• PMID: 18950807 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• 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, genetics)