A Study for Treatment of Superficial Bladder Cancer Using OGX-427

• ClinicalTrials.gov Identifier: NCT00959868
• Recruitment Status: Unknown
• First Posted: August 17, 2009
• Last Update Posted: February 13, 2012
• Sponsor: Vancouver Coastal Health
• Collaborators: NCIC Clinical Trials Group; Vancouver General Hospital Foundation
• Information provided by: Vancouver Coastal Health

Tracking Information

• First Submitted Date: August 13, 2009
• First Posted Date: August 17, 2009
• Last Update Posted Date: February 13, 2012
• Study Start Date: July 2009
• Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 10, 2012)

• To define the maximum tolerated dose (MTD) of OGX-427 administered as an intravesical instillation. [ Time Frame: One year ]
  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 ]
  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)

• Original Primary Outcome Measures (submitted: August 14, 2009): To define the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of OGX-427 (Vorinostat) administered as an intravesical instillation. [ Time Frame: On each visit: Days 1, 3, 5 and 8 ]

Current Secondary Outcome Measures (submitted: February 10, 2012)

• To determine the toxicity profile of OGX-427 when administered intravesically. [ Time Frame: One year ]
• To measure evidence of OGX-427 effect on expression of Hsp27. [ Time Frame: one year ]
• To determine the bladder PK and PD profile of OGX-427 after intravesical administration. [ Time Frame: one year ]

• Original Secondary Outcome Measures (submitted: August 14, 2009): To determine the toxicity profile of OGX-427 when administered intravesically. To measure evidence of OGX-427 effect on expression of Hsp27. To determine the bladder PK and PD profile of OGX-427 after intravesical administration. [ Time Frame: On each visit: Days 1, 3, 5, and 8 (for PK and PD profile); Days 1, 3, 5, 8 and 38 (for Toxicity profile) ]
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study for Treatment of Superficial Bladder Cancer Using OGX-427
• Official Title: A Phase I Clinical Trial Assessing Intravesical Antisense Oligonucleotide Targeting Heat Shock Protein 27 for the Treatment of Superficial Bladder Cancer

Brief Summary

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Bladder Cancer

Intervention

Drug: OGX-427

OGX-427 drug product is in 25mg/mL injection in a mannitol-phosphate buffer solution packaged to deliver at least 8mL volume from a 10mL Type I, clear glass vial (ammonium sulfate treated) with Teflon coated bromobutyl rubber stopper and sealed with an aluminum, red, flip-off over seal. The drug product is aseptically compounded and sterilized via sterile filtration prior to aseptic filling.

• Study Arms: Not Provided
• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: August 14, 2009): 36
• Original Estimated Enrollment: Same as current
• Study Completion Date: Not Provided
• Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Patient age must be > 18

2. Histologic evidence of bladder cancer (superficial or muscle invasive) or

   CIS as evidenced by:

   • Patients presenting with superficial tumours and unknown pathological stage will have in-clinic bladder washings (performed cystoscopically) and biopsy (cup biopsy).

   • Patients with recurrent superficial disease (Ta or T1) and tissue that is available for baseline studies (i.e. tissue from previous transurethral resection stored in paraffin blocks) will be eligible for trial without requiring cytology or biopsy.

     • Patients with previously diagnosed T1 tumours and requiring re-resection of bladder tumour will be eligible if tissue from the original TURBT is available for baseline studies.
     • Patients presenting as muscle invasive (>T2) disease will be eligible if they are candidates for radical cystectomy and if baseline tissue from initial resections is available for baseline studies
3. No intravesical therapies within the previous 6 months
4. No evidence of metastatic disease as determined by physical exam, CT scan or chest- x-ray, where indicated.
5. ECOG status must be 0, 1, or 2

6. Laboratory requirements (within 7 days of treatment):

   • negative urine cultures
   • Absolute neutrophils count> 1.5 x 109 cells/L, and platelets count> 100 x 109/L,
   • Total bilirubin < 1.5 x upper normal limit (ULN), AST and/or ALT < 1.5 x ULN, alkaline phosphatase < 1.5 x ULN, and serum creatinine < 1.5 x ULN.
   • PTT and INR, within normal limits
7. Patient must be able to complete the quality of life questionnaires in either English or French
8. Patients must provide written informed consent.

Exclusion Criteria:

1. Patients with "indeterminate" or "negative" results from biopsy or cytology will be ineligible for the trial.
2. Patients taking warfarin or Coumadin anticoagulation therapy or who have a bleeding disorder. NOTE: Patients who require anticoagulation therapy while on study will be removed from study treatment.
3. Pregnant or lactating women
4. Patients not accessible for follow-up
5. Patients with an active urinary tract infection, upper tract urothelial tumors, active infection including tuberculosis, concurrent febrile illness or impaired immune response from any cause
6. Patients with contraindication to spinal or general anesthesia required for a transurethral resection or radical cystectomy
7. Recent (<14 days) urethral trauma or inability to perform catheterization or cystoscopy safely
8. Patients known to have a serious illness or medical condition that would impair protocol treatment delivery.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada

Administrative Information

• NCT Number: NCT00959868
• Other Study ID Numbers: BL-01
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Alan I. So, MD, FRCSC, Vancouver Coastal Health
• Study Sponsor: Vancouver Coastal Health

Collaborators

• NCIC Clinical Trials Group
• Vancouver General Hospital Foundation

Investigators

• Principal Investigator: Alan I So, MD, FRCSC; Vancouver Coastal Health

• PRS Account: Vancouver Coastal Health
• Verification Date: February 2012