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

Titre officiel

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").

Sommaire:

Il s’agit d’une étude ouverte de phase II, multicentrique et à un seul groupe, menée au Canada, aux États-Unis et à l’échelle internationale. Patients atteints d’un carcinome in situ (CIS) de la vessie sans envahissement musculaire avec ou sans maladie papillaire réséquée (Ta, T1) considérés comme ne répondant pas au traitement par le bacille de Calmette-Guérin (BCG) ou ne le tolérant pas. Absence de réponse au BCG correspondant à un des profils suivants : Au moins cinq des six doses d’un traitement d’induction initial et au moins deux des trois doses du traitement d’entretien; OU, au moins cinq des six doses d’un traitement d’induction initial et au moins deux des six doses d’un deuxième traitement d’induction. Les patients présentant une récidive de la maladie moins de 12 mois après la fin du deuxième cycle de traitement par le BCG sont également considérés comme ne répondant pas au traitement. L’étude comprendra 100 patients qui subiront deux (2) traitements photodynamiques utilisant 0,70 mg/cm^2 de TLD-1433 le jour 0 et le jour 180.

Description de l'essai

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.

Voir cet essai sur ClinicalTrials.gov

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