Safety and Proof of Concept Study of Intravesical DTA-H19 in Patients With Superficial Bladder Cancer

This study has been completed.
Sponsor:
Collaborator:
BioCancell Ltd.
Information provided by:
Hebrew University of Jerusalem
ClinicalTrials.gov Identifier:
NCT00393809
First received: October 26, 2006
Last updated: December 25, 2007
Last verified: December 2007

October 26, 2006
December 25, 2007
January 2006
November 2007   (final data collection date for primary outcome measure)
The maximum tolerated dose (MTD)
Same as current
Complete list of historical versions of study NCT00393809 on ClinicalTrials.gov Archive Site
  • The percentage increase or reduction in the area of marker lesions
  • The number of patients with progressive disease
  • The time to disease progression
Same as current
Not Provided
Not Provided
 
Safety and Proof of Concept Study of Intravesical DTA-H19 in Patients With Superficial Bladder Cancer
Phase 1/2a, Dose-Escalation, Safety and Proof of Concept Study of Intravesical DTA-H19 in Patients With Superficial Bladder Cancer

This study is designed to assess the safety and preliminary efficacy of five different doses of DTA-H19 given as six intravesical infusions into the bladder of patients with superficial bladder cancer who have failed intravesical therapy with Bacille Calmette-Guérin (BCG).DTA-H19 is a DNA plasmid that contains H19 gene regulatory sequences that drive the expression of an intracellular toxin [diphtheria toxin A (DTA) chain]only in cancer cells and not in normal cells. In line with the standard procedure for DNA plasmid pharmaceutical products, another chemical component will be added to the solution, called PEI (polyethlenimine) in a liquid solution, which improves the ability of the DNA plasmid to enter the cells.

This study is designed to assess the safety and preliminary efficacy of five different doses of DTA-H19 given as six intravesical infusions into the bladder of patients with superficial bladder cancer [stages Ta and carcinoma in situ (CIS)] who have failed intravesical therapy with Bacille Calmette-Guérin (BCG). The primary safety outcome measure is the maximum tolerated dose (MTD). DTA-H19 is a DNA plasmid that contains H19 gene regulatory sequences that drive the expression of an intracellular toxin [diphtheria toxin A (DTA) chain]. This is a Patient-Oriented, Targeted Therapy as DTA expression is triggered by the presence of H19 transcription factors found only in bladder tumor and not normal bladder cells.

A maximum of 18 patients with histologically confirmed H19 positive superficial bladder cancer with multiple or recurrent stage Ta tumors or CIS will be included in this study. Patients with any grade 3, or any stage T1 or higher stage, will be excluded. This is a multicenter, dose escalation study in which, after eligibility criteria have been met, patients in five groups of 3 patients each, will receive escalating doses of DTA-H19 intravesically over a seven-week period. Treatments will be given weekly for three weeks followed one week later by safety and disease assessments, then another 3 weekly instillations will be performed. Each dose cohort will receive the same dose for all treatments. The first dose cohort will receive 2 mg of DTA-H19 plasmid per intravesical treatment for all treatments. The next dose cohort of 3 patients will receive 4 mg, the next 6 mg, the next 12 mg,and then the final dose cohort will receive 20 mg of DTA-H19 plasmid DNA. All doses will be mixed with polyethylenimine (PEI) to improve transduction efficiency. Doses will be escalated if none of the first three patients in the preceding dose cohort experience a dose limiting toxicity (DLT) after the first three weekly intravesical treatments.

Clinical responses will be assessed 4, 8, and 12 weeks after the start of treatment. If the stage Ta marker lesion is still present at the week 12 assessment, it will be resected by transurethral resection (TUR). Patients whose disease has not progressed (i.e., no new lesions, increase in the size of the marker lesion, by at least 50%, or increase in stage or any grade 3) will be offered continued once monthly treatments and follow-up for up to one year

Interventional
Phase 1
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Bladder Neoplasms
Drug: DTA-H19
Not Provided
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
18
December 2007
November 2007   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patients must have superficial transitional cell carcinoma of the bladder (stages Ta and/or CIS)
  • Tumor biopsies must be shown to be positive for H19 gene by in situ hybridization
  • Patients must have failed intravesical treatment with BCG

Exclusion Criteria:

  • Patients with grade 3, or Stage 1 or higher stage TCC of the bladder
  • Patients with any other malignancy that might impact 5-year survival or might be potentially confused with TCC
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Israel
 
NCT00393809
BC-05-02.CTIL
Not Provided
Not Provided
Hebrew University of Jerusalem
BioCancell Ltd.
Principal Investigator: Abraham Sidi, MD E. Wolfson Medical Center
Principal Investigator: Ilan Leibovitch, MD Meir Medical Center
Hebrew University of Jerusalem
December 2007

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP