A Study for Treatment of Superficial Bladder Cancer Using OGX-427
This is a single centre, open label, phase I dose escalation trial using a modified accelerated titration design. Patients with superficial bladder tumour (Ta or T1) or CIS and candidates for transurethral resection or muscle invasive disease (>T2) and candidates for radical cystectomy will be enrolled.
OGX-427 will be given neoadjuvantly over 8 days, followed by a transurethral resection (for superficial disease) or radical cystectomy (for muscle invasive disease).
Baseline Hsp27 levels will be determined from pre-treatment cytological samples from bladder washings and tumour biopsies performed prior to therapy.
Post-treatment PK and PD data will be determined from TUR (for Ta, T1 tumours) or radical cystectomy (for T2 tumours) specimens. A recommended phase II dose will be determined from the toxicity, tissue pK, and percentage of Hsp27 knockdown. Effects of treatment on Hsp27 client protein levels and apoptotic index will also be evaluated.
Evaluation during protocol treatment will take place to assess toxicity. Assessments will occur on various visits as per Evaluation Schedule. Adverse event evaluation based on NCI CTCAEv3.0. For quality of life assessment during treatment, the EORTC QLC-BLS24 will be used before first treatment (day 1) and prior to surgery (TURBT or radical cystectomy). The Day 1 QOL assessment will serve as baseline.
After removal from protocol treatment, all subjects will be followed for toxicity related to study drug for 30 days.
After the study, subjects will be followed according to standard of care. Follow-up for tumour recurrence or superficial tumours will be assessed every three months by cystoscopic examination for two years, then every six months for the next two years, and then yearly thereafter.
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Clinical Trial Assessing Intravesical Antisense Oligonucleotide Targeting Heat Shock Protein 27 for the Treatment of Superficial Bladder Cancer|
- To define the maximum tolerated dose (MTD) of OGX-427 administered as an intravesical instillation. [ Time Frame: One year ] [ Designated as safety issue: Yes ]The study medication will be escalated according to a fixed dose escalation plan. Three subjects will be treated per cohort. If one of the three subjects experiences a DLT, three additional subjects will be treated at that dose level (i.e. maximum of 6 subjects per cohort)
- To define the dose-limiting toxicities (DLTs) of OGX-427 administered as an intravesical instillation. [ Time Frame: one year ] [ Designated as safety issue: Yes ]The study medication will be escalated according to a fixed dose escalation plan. Three subjects will be treated per cohort. If one of the three subjects experiences a DLT, three additional subjects will be treated at that dose level(i.e. maximum of 6 subjects per cohort)
- To determine the toxicity profile of OGX-427 when administered intravesically. [ Time Frame: One year ] [ Designated as safety issue: No ]
- To measure evidence of OGX-427 effect on expression of Hsp27. [ Time Frame: one year ] [ Designated as safety issue: No ]
- To determine the bladder PK and PD profile of OGX-427 after intravesical administration. [ Time Frame: one year ] [ Designated as safety issue: No ]
|Study Start Date:||July 2009|
|Estimated Primary Completion Date:||December 2012 (Final data collection date for primary outcome measure)|
|Contact: Maureen Palmer, RN||604-875-5675||Maureen.Palmer@vch.ca|
|Canada, British Columbia|
|The Prostate Centre at Vancouver General Hospital||Recruiting|
|Vancouver, British Columbia, Canada, V5Z 1M9|
|Contact: Maureen Palmer, RN 604-875-5675 Maureen.Palmer@vch.ca|
|Principal Investigator: Alan I So, MD, FRCSC|
|Sub-Investigator: Peter C Black, MD, FRCSC|
|Sub-Investigator: Edward C Jones, MD, FRCPC, LMCC|
|Principal Investigator:||Alan I So, MD, FRCSC||Vancouver Coastal Health|