Dose Escalation Study With QLT0074 for Benign Prostatic Hyperplasia
The primary objective of this study is to assess the safety and tolerance of transurethral photodynamic therapy (PDT) with QLT0074.
Secondary objectives are:
- To determine if transurethral PDT with QLT0074 has a therapeutic effect on benign prostatic hyperplasia (BPH), evaluated by the American Urological Association Symptom Index (AUA SI), urinary flow rate (Qmax), and post-void residual volume (PVR).
- To determine the extent of systemic exposure to QLT0074 following transurethral intraprostatic injection.
- To select up to two transurethral PDT drug-light regimens for further clinical development.
Benign Prostatic Hyperplasia
Drug: Photodynamic therapy
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I/II Dose Escalation Study to Assess the Safety, Tolerability, and Preliminary Efficacy of Transurethral Photodynamic Therapy With QLT0074 for Benign Prostatic Hyperplasia|
|Study Start Date:||March 2003|
|Study Completion Date:||May 2005|
|Primary Completion Date:||May 2005 (Final data collection date for primary outcome measure)|
This will be a multicenter, uncontrolled, dose escalation, exploratory study in subjects with symptomatic BPH. Six study centers are planned.
Each subject will receive a fixed dose of QLT0074 (0.4 mg) injected transurethrally into the prostate followed by transurethral light application to activate the drug. Five light dose cohorts will be investigated sequentially (25, 50, 80, 120, and 150 J/cm2), with 3 subjects in the first cohort and 6 subjects in cohorts 2-5 for a total of 27 subjects. The follow-up period for each subject is 180 days. There will be a minimum 30-day interval between treatment of the last subject in one cohort (Day 0) and treatment of the first subject in the next cohort to monitor predefined toxicities and ensure safety and tolerance in subjects of the previous cohort.
A Safety Monitoring Committee will evaluate toxicity related to PDT effects, and approve escalation of the light dose for each cohort. The light dose will not be escalated if any of the following predefined toxicity criteria occur and are judged to be related to a PDT effect by the Safety Monitoring Committee:
- 1 or more subjects in the cohort experience macroscopic urinary bleeding not resolved by Day 14, or
- 2 or more subjects in the cohort experience intolerable urinary pain not controlled with over-the-counter medication by Day 14, or
- 1 or more subjects in the cohort experience any other clinically significant urological adverse event, as judged by the Investigator and confirmed by the Safety Monitoring Committee.
In addition to the above events, the Safety Monitoring Committee will evaluate the incidence, timing, severity, and frequency of other adverse events and serious adverse events to assess the safety of transurethral PDT and the treatment procedures (such as the use of the cystoscope, InjectTx device, treatment balloon-catheter, etc).
To prevent treating subjects with a light dose greater than that which already provides substantial clinical benefit, the Safety Monitoring Committee will review preliminary efficacy data (AUA SI scores and Qmax values) after all subjects in a cohort (for each of the first 4 cohorts) have completed the Day 90 visit. Further enrollment will be curtailed if more than 75% of subjects in a cohort experience both of the following efficacy stopping criteria by Day 90:
- greater or equal to 75% reduction in the AUA SI score and,
- greater or equal to 100% increase in Qmax.
|United States, California|
|Raymond Fay, MD, Inc|
|San Francisco, California, United States, 94108|
|United States, District of Columbia|
|George Washington University Medical Center|
|Washington, District of Columbia, United States, 20037|
|United States, Florida|
|Advanced Research Institute Inc|
|New Port Richey, Florida, United States, 34652|
|United States, South Carolina|
|Carolina Urologic Research Center|
|Myrtle Beach, South Carolina, United States, 29572|
|United States, Texas|
|North Texas Veteran Affairs Health Care System|
|Dallas, Texas, United States, 75216|
|Canada, British Columbia|
|The Prostate Centre at Vancouver General Hospital|
|Vancouver, British Columbia, Canada, V5Z 3J5|
|Royal Victoria Hospital|
|Montreal, Quebec, Canada, H3A 1A1|