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

Primary Purpose

Bladder Cancer

Status

Unknown status

Phase

Phase 1

Locations

Canada

Study Type

Interventional

Intervention

OGX-427

About this trial

This is an interventional treatment trial for Bladder Cancer focused on measuring Bladder cancer, Superficial bladder cancer (Ta or T1), Muscle invasive bladder cancer (T2), Transurethral resection, Radical cystectomy, OGX-427, Antisense oligonucleotide, Heat shock protein 27, superficial bladder tumour (Ta or T1) or CIS prior to a transurethral resection, Muscle invasive (T2) bladder cancer prior to radical cystectomy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patient age must be > 18
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
No intravesical therapies within the previous 6 months
No evidence of metastatic disease as determined by physical exam, CT scan or chest- x-ray, where indicated.
ECOG status must be 0, 1, or 2
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
Patient must be able to complete the quality of life questionnaires in either English or French
Patients must provide written informed consent.

Exclusion Criteria:

Patients with "indeterminate" or "negative" results from biopsy or cytology will be ineligible for the trial.
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.
Pregnant or lactating women
Patients not accessible for follow-up
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
Patients with contraindication to spinal or general anesthesia required for a transurethral resection or radical cystectomy
Recent (<14 days) urethral trauma or inability to perform catheterization or cystoscopy safely
Patients known to have a serious illness or medical condition that would impair protocol treatment delivery.

Sites / Locations

The Prostate Centre at Vancouver General HospitalRecruiting

Outcomes

Primary Outcome Measures

To define the maximum tolerated dose (MTD) of OGX-427 administered as an intravesical instillation.

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.

Secondary Outcome Measures

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.

Full Information

NCT ID

NCT00959868

First Posted

August 13, 2009

Last Updated

February 10, 2012

Sponsor

Vancouver Coastal Health

Collaborators

NCIC Clinical Trials Group, Vancouver General Hospital Foundation

1. Study Identification

Unique Protocol Identification Number

NCT00959868

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

Study Type

Interventional

2. Study Status

Record Verification Date

February 2012

Overall Recruitment Status

Unknown status

Study Start Date

July 2009 (undefined)

Primary Completion Date

December 2012 (Anticipated)

Study Completion Date

undefined (undefined)

3. Sponsor/Collaborators

Name of the Sponsor

Vancouver Coastal Health

Collaborators

NCIC Clinical Trials Group, Vancouver General Hospital Foundation

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Bladder Cancer

Keywords

Bladder cancer, Superficial bladder cancer (Ta or T1), Muscle invasive bladder cancer (T2), Transurethral resection, Radical cystectomy, OGX-427, Antisense oligonucleotide, Heat shock protein 27, superficial bladder tumour (Ta or T1) or CIS prior to a transurethral resection, Muscle invasive (T2) bladder cancer prior to radical cystectomy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

36 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type

Drug

Intervention Name(s)

OGX-427

Intervention Description

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.

Primary Outcome Measure Information:

Title

To define the maximum tolerated dose (MTD) of OGX-427 administered as an intravesical instillation.

Description

Time Frame

One year

Title

To define the dose-limiting toxicities (DLTs) of OGX-427 administered as an intravesical instillation.

Description

Time Frame

one year

Secondary Outcome Measure Information:

Title

To determine the toxicity profile of OGX-427 when administered intravesically.

Time Frame

One year

Title

To measure evidence of OGX-427 effect on expression of Hsp27.

Time Frame

one year

Title

To determine the bladder PK and PD profile of OGX-427 after intravesical administration.

Time Frame

one year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patient age must be > 18 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 No intravesical therapies within the previous 6 months No evidence of metastatic disease as determined by physical exam, CT scan or chest- x-ray, where indicated. ECOG status must be 0, 1, or 2 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 Patient must be able to complete the quality of life questionnaires in either English or French Patients must provide written informed consent. Exclusion Criteria: Patients with "indeterminate" or "negative" results from biopsy or cytology will be ineligible for the trial. 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. Pregnant or lactating women Patients not accessible for follow-up 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 Patients with contraindication to spinal or general anesthesia required for a transurethral resection or radical cystectomy Recent (<14 days) urethral trauma or inability to perform catheterization or cystoscopy safely Patients known to have a serious illness or medical condition that would impair protocol treatment delivery.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Maureen Palmer, RN

Phone

604-875-5675

Maureen.Palmer@vch.ca

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Alan I So, MD, FRCSC

Organizational Affiliation

Vancouver Coastal Health

Official's Role

Principal Investigator

Facility Information:

Facility Name

The Prostate Centre at Vancouver General Hospital

City

Vancouver

State/Province

British Columbia

ZIP/Postal Code

V5Z 1M9

Country

Canada

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Maureen Palmer, RN

Phone

604-875-5675

Maureen.Palmer@vch.ca

First Name & Middle Initial & Last Name & Degree

Alan I So, MD, FRCSC

First Name & Middle Initial & Last Name & Degree

Peter C Black, MD, FRCSC

First Name & Middle Initial & Last Name & Degree

Edward C Jones, MD, FRCPC, LMCC

12. IPD Sharing Statement

Learn more about this trial

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

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