Official Title
A Phase II Clinical Study of Intravesical Photodynamic Therapy in Patients With BCG-Unresponsive Non-Muscle Invasive Bladder Cancer ("NMIBC") Or Patients Who Are Intolerant to BCG Therapy ("Study").
Summary:
This is a phase II, open-label, single-arm, multi-centre Study conducted in Canada, the
United States and internationally. Patients with NMIBC CIS with or without resected papillary
disease (Ta, T1) that are considered bacillus Calmette-Guerin (BCG)-Unresponsive or who are
intolerant to BCG therapy. BCG-Unresponsive is at least one of the following: At least five
of six doses of an initial induction course plus at least two of three doses of maintenance
therapy; OR, At least five of six doses of an initial induction course plus at least two of
six doses of a second induction course. Patients experiencing disease relapse less than 12
months after finishing the second course of BCG therapy are also considered BCG-Unresponsive.
The Study will consist of 100 patients who will undergo two (2) PDT treatments employing 0.70
mg/cm^2 of TLD-1433 at Day 0 and Day 180.
Trial Description
Primary Outcome:
- Efficacy, evaluated by the Complete Response (CR) rate.
Secondary Outcome:
- Safety, evaluated by the incidence and severity of Adverse Events.
- Overall Study Design and Plan: Description This is a
phase II, open-label, single-arm, multi-centre 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).
- 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 28 days.
- 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 12 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
and 360.
- 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 centre 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 A single whole bladder intravesical PDT
with TLD-1433 and the TLC-3200 System is planned. Two treatment procedures will
be performed, a primary treatment at Day 0 and a secondary treatment at Day 180
post primary treatment.
4.2 PDT Disruption Patients with NMIBC CIS with or without
resected papillary disease (Ta, T1) that are considered 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 cystoscopy for laser light
application (maximum 8 weeks after TURBT), a patient will be rescheduled for a
TURBT procedure to resect the papillary tumour(s) and a new treatment procedure
date will be set, even though previously instilled with TLD-1433.
View this trial on ClinicalTrials.gov
