Intravesical Photodynamic Therapy (PDT) in BCG Refractory/Intolerant Non-Muscle Invasive Bladder Cancer (NMIBC) Patients

Description

1. Overall Study Design and Plan: Description

This is a phase II, open-label, single-arm, multi-center Study conducted in Canada, the United States and internationally. Patients with NMIBC CIS with or without resected papillary disease (Ta, T1) that are considered BCG-Unresponsive or are intolerant to BCG therapy that meet the inclusion and exclusion criteria will be enrolled and treated. The Study will consist of 100 patients who will receive PDT employing 0. 70 mg/cm^2 (Therapeutic Dose).

2. Screening Period

Patients will be qualified for Study entry by review of inclusion and exclusion criteria during the Screening Period, which will last up to 45 days.

3. Follow-Up Phase

All patients enrolled and treated by the treatment procedure will be followed until the End of Study defined as completion of all required assessments after 15 months of follow-up post treatment or earlier due to early discontinuation or withdrawal of informed consent.

During the Follow-Up Phase, information on efficacy and safety will be collected. Assessments will be conducted at Day 0, 7, 30, 60, 90, 180, 187, 210, 240, 270, 360 and 450 days.

4. Study Drug and PDT Administration

TLD-1433 for intravesical administration is supplied as a lyophilisate for suspension in Sterile Water for Injection into the bladder and is packaged in the dark in amber USP Type III glass vials which can be stored at room temperature. Up to 24 hours before administration, it is reconstituted with Sterile Water for Injection to obtain the final clinical dilution.

TLD-1433 will be supplied to each Study site by Theralase. Instillations cannot be done immediately following biopsy taken by TURBT. Investigators must wait a minimum of 7 days before dosing patients after a TURBT/biopsy, and/or until any bladder wall integrity issues have resolved. Dose/volume reductions are not allowed during this Study.

Upon determination of the bladder volume (during the screening period) through a voiding diary or measuring instilled water volume, TLD-1433 to be instilled will be diluted to the proper concentration. On day 0 (treatment day), patients will be asked to restrict fluid intake 12 hours before Study Drug instillation. Study drug must be instilled into the patient's empty bladder. Before instillation, a regular transurethral catheter should be inserted and the bladder drained. A single instillation of TLD-1433 will be infused intravesically for approximately 60 minutes, followed by 3 washes with sterile water. The bladder will be distended using a fourth instillation of sterile water to prevent folds that may prevent uniform light illumination. The laser technician worksheet must be completed during the procedure and data must be promptly transferred to the corresponding electronic Case Report Form ("eCRF") page.

Insertion of the optical fiber with spherical diffuser into the bladder will be monitored under ultrasonic guidance. The optical fiber with spherical diffuser will be positioned in the geometric center of the bladder with the aid of TLC-3200 and will be locked into place using an endoscope holder for continuous irradiation for the total exposure time. Exposure time will be calculated based on power emitted from the end of the optic fiber. The optic fiber is inserted through a liquid-tight lock via a catheter into the urethra. The optical power and treatment time will be determined to provide the correct dose of laser light to the bladder surface area. Green laser light (wavelength = 532 nm, energy = 90 J/cm2) will be irradiated from the emitter optical fiber via the spherical diffuser. The bladder volume may be monitored during the procedure and water instilled or drained, as required, to keep the bladder volume as consistent as possible.

4.1 Dosing Schedule

Two treatment procedures are planned, a primary treatment at Day 0 and a secondary treatment at Day 180 post primary treatment. Each treatment procedure is a single whole bladder intravesical PDT with TLD-1433 and the TLC-3200 System.

4.2 PDT Disruption

Patients with persistent or recurrent NMIBC CIS alone or with recurrent Ta/T1 (noninvasive papillary disease/tumour invades the subepithelial connective tissue) disease within 12 months of completion of BCG therapy (BCG-Unresponsive) or who are intolerant to BCG therapy will be treated with this Protocol. If one or more papillary tumours are seen at the time of Study Treatment (maximum 12 weeks after TURBT), the patient will be resected and will be treated with this Protocol.

Details