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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00393809
First Posted: October 30, 2006
Last Update Posted: January 7, 2008
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
BioCancell Ltd.
Information provided by:
Hebrew University of Jerusalem
  Purpose
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.

Condition Intervention Phase
Bladder Neoplasms Drug: DTA-H19 Phase 1 Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1/2a, Dose-Escalation, Safety and Proof of Concept Study of Intravesical DTA-H19 in Patients With Superficial Bladder Cancer

Resource links provided by NLM:


Further study details as provided by Hebrew University of Jerusalem:

Primary Outcome Measures:
  • The maximum tolerated dose (MTD)

Secondary Outcome Measures:
  • The percentage increase or reduction in the area of marker lesions
  • The number of patients with progressive disease
  • The time to disease progression

Enrollment: 18
Study Start Date: January 2006
Study Completion Date: December 2007
Primary Completion Date: November 2007 (Final data collection date for primary outcome measure)
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 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

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00393809


Locations
Israel
E. Wolfson Medical Center
Holon, Israel
Meir Medical Center
Kfar Saba, Israel
Sponsors and Collaborators
Hebrew University of Jerusalem
BioCancell Ltd.
Investigators
Principal Investigator: Abraham Sidi, MD E. Wolfson Medical Center
Principal Investigator: Ilan Leibovitch, MD Meir Medical Center
  More Information

ClinicalTrials.gov Identifier: NCT00393809     History of Changes
Other Study ID Numbers: BC-05-02.CTIL
First Submitted: October 26, 2006
First Posted: October 30, 2006
Last Update Posted: January 7, 2008
Last Verified: December 2007

Keywords provided by Hebrew University of Jerusalem:
transitional cell carcinoma
H19 gene
plasmid
diphtheria toxin

Additional relevant MeSH terms:
Urinary Bladder Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Urinary Bladder Diseases
Urologic Diseases