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

Bladder Neoplasms Clinical Trial

Official title:

Phase 1/2a, Dose-Escalation, Safety and Proof of Concept Study of Intravesical DTA-H19 in Patients With Superficial Bladder Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00393809
• Other study ID #: BC-05-02.CTIL
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: October 26, 2006
• Last updated: December 25, 2007
• Start date: January 2006
• Est. completion date: December 2007

Study information

• Verified date: December 2007
• Source: Hebrew University of Jerusalem
• Contact: n/a
• Is FDA regulated: No
• Health authority: Israel: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: December 2007
• Est. primary completion date: November 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bladder Neoplasms
• Urinary Bladder Neoplasms

Intervention

Drug:
• DTA-H19

Locations

Country	Name	City	State
Israel	E. Wolfson Medical Center	Holon
Israel	Meir Medical Center	Kfar Saba

Sponsors (2)

Lead Sponsor	Collaborator
Hebrew University of Jerusalem	BioCancell Ltd.

Country where clinical trial is conducted

Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The maximum tolerated dose (MTD)
Secondary	The percentage increase or reduction in the area of marker lesions
Secondary	The number of patients with progressive disease
Secondary	The time to disease progression