Phase 2b, Trial of Intravesical DTA-H19/PEI in Patients With Intermediate-Risk Superficial Bladder Cancer
This study is designed to assess the efficacy and safety of DTA-H19/PEI given as six intravesical instillations of 20 mg of plasmid DNA complexed with PEI into the bladder of patients with intermediate risk superficial bladder cancer [recurrent stages Ta (low or high grade)and T1, (low grade) transitional cell carcinoma (TCC)] who have failed prior intravesical therapies including either Bacillus Calmette-Guérin (BCG) or chemotherapy. The primary efficacy objective is to determine the effect of DTA-H19/PEI on the prevention of new tumors after the induction course of 6 weekly intravesical administrations of investigational product assessed 8 to 10 weeks after the start of treatment. Secondary objectives include assessing the ablative effect of DTA-H19/PEI on a marker tumor, safety assessed by the incidence and severity of adverse events, determining the long-term (46 weeks) continued rates of absence of bladder cancer, and time to tumor recurrence in those patients who had a complete response (CR) after the induction course.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase 2b, Multicenter Trial of Intravesical DTA-H19/PEI in Patients With Intermediate-Risk Superficial Bladder Cancer|
- Complete Tumor Response Defined as the Absence of New Tumors [ Time Frame: 9 Weeks ] [ Designated as safety issue: No ]Tumor response evaluated at week 9 (range 8-10 weeks) during the first post induction course treatment cystoscopy or TUR of suspiciaous lesions
- Time to Tumor Recurrence [ Time Frame: 46 Weeks ] [ Designated as safety issue: No ]The Time to Tumor Recurrence is defined as the interval between the date of the final tumor resection before the start of study treatments to the date when the cystoscopy was performed in which it was confirmed by histopathology that any suspicious lesions that were observed, were TCC of the bladder with the exception of the continued presence of the marker tumor at Week 9
- Ablative Effect on a Marker Tumor [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]Complete disappearance of marker lesion
- Safety [ Time Frame: 9 weeks ] [ Designated as safety issue: Yes ]the incidence and severity of adverse events
|Study Start Date:||January 2008|
|Estimated Study Completion Date:||October 2014|
|Primary Completion Date:||January 2013 (Final data collection date for primary outcome measure)|
Experimental: 20 mg of BC-819/PEI
Six intravesical instillations of 20 mg of plasmid DNA (BC-819) complexed with PEI into the bladder of patients with intermediate-risk superficial bladder cancer [recurrent stages Ta (low or high grade) and T1 (low grade) TCC] who have failed prior intravesical therapies including BCG and/or chemotherapy.
Papillary tumors will be resected with the exception of one marker tumor that will remain to examine the effects of the treatment on the remaining tumor. Study treatments will consist of an induction course of six weekly instillations of 20 mg of DTA-H19/PEI into the urinary bladder. Intravesical therapy will be delivered through a Foley catheter. Patients will be instructed to hold the dose in the bladder for two hours after administration. If the patient has a complete response, then she/he will be eligible to receive three additional courses of 3 weekly intravesical administrations of the same dose of investigational product every 12 weeks.
Other Name: DTA-H19
DTA-H19, is a doubled stranded DNA plasmid that carries the gene for the diphtheria toxin A (DT-A) chain under the regulation of the H19 promoter sequence. This is a Patient-Oriented, Targeted Therapy as DT-A chain expression is triggered by the presence of H19 transcription factors that are upregulated in tumor cells. The selective initiation of toxin expression results in selective tumor cell destruction via inhibition of protein synthesis in the tumor cell, enabling highly targeted cancer treatment.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00595088
|United States, Arizona|
|Phoenix, Arizona, United States, 85032|
|Bnai Zion Medical Center|
|Edith Wolfson Medical Center|
|Hadassah and Hebrew University Medical Center|
|Meir Medical Center|
|Kfar Saba, Israel|
|Principal Investigator:||Donald Lamm, MD||University of Arizona and BCG Oncolgy|