1. Overall Study Design and Plan: Description
This is a phase II, open-label, single-arm, multi-center Study conducted in Canada
and the United States. 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 approximately 100 to 125 patients who will receive PDT
employing 0.70 mg/cm^2 (Therapeutic Dose).
2. Screening Period
Patients will be qualified for Study II 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 primary study treatment or 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
Ruvidar® (TLD-1433) for intravesical administration is supplied as a lyophilisate for
suspension in Sterile Water For Injection ("SWFI") into the bladder and is packaged in
the dark in amber USP Type III glass vials, which are stored at 3 to 8 degree Celsius. Up
to 24 hours before administration, it is reconstituted with SWFI to obtain the final
clinical dilution.
Ruvidar® (TLD-1433) will be supplied to each Study II site by Theralase®. Instillations
cannot be done immediately following biopsy taken by Trans-Urethral Resection of Bladder
Tumour ("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 Study II.
Upon determination of the bladder volume (during the screening period) through a
self-recorded voiding diary, Ruvidar® (TLD-1433) will be diluted with SWFI to the proper
concentration. On day 0 (Primary Study 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 Ruvidar® (TLD-1433) will be
infused intravesically for approximately 60 minutes, followed by 1 wash with SWFI. The
bladder will be distended using a second instillation of SWFI to prevent folds that may
prevent uniform light illumination. The Computer Operator worksheet must be completed
during the Study Treatment and data must be promptly transferred to the corresponding
electronic Case Report Form ("eCRF") page.
Positioning 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 through the cystoscope 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. 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.
4.1 Dosing Schedule
Two Study Treatments are planned, a primary Study Treatment at Day 0 and a maintenance
Study Treatment at Day 180. Each Study Treatment is a single whole bladder intravesical
PDT with Ruvidar® (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.