Ignite Creation Date:
2024-05-05 @ 5:09 PM
Last Modification Date:
2024-10-26 @ 9:28 AM
Study NCT ID:
NCT00393809
Status:
COMPLETED
Last Update Posted:
2008-01-07
First Post:
2006-10-26
Brief Title:
Safety and Proof of Concept Study of Intravesical DTA-H19 in Patients With Superficial Bladder Cancer
Sponsor:
Hebrew University of Jerusalem
Organization:
Hebrew University of Jerusalem
Study Overview
Official Title:
Phase 12a Dose-Escalation Safety and Proof of Concept Study of Intravesical DTA-H19 in Patients With Superficial Bladder Cancer
Status:
COMPLETED
Status Verified Date:
2007-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 BCGDTA-H19 is a DNA plasmid that contains H19 gene regulatory sequences that drive the expression of an intracellular toxin diphtheria toxin A DTA chainonly 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
Detailed 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 mgand 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 ie 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
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 mgand 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 ie 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None