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

Last updated: April 27, 2023
Sponsor: Theralase® Technologies Inc.
Overall Status: Active - Recruiting

Phase

2

Condition

Urothelial Cancer

Bladder Cancer

Treatment

Ruvidar® (TLD-1433) Bladder infusion and PDT

Clinical Study ID

NCT03945162
Ruvidar® (TLD-1433) NMIBC PDT
  • Ages > 18
  • All Genders

Study Summary

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 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 within 12 months after finishing the second course of BCG therapy are considered BCG-Unresponsive. The Study will consist of approximately 100 to 125 patients who will undergo two (2) PDT treatments employing 0.70 mg/cm^2 of Ruvidar® (TLD-1433) at Day 0 and Day 180.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. Be willing and able to provide a written Informed Consent Form ("ICF") for the Study.
  2. Be > 18 years of age on day of signing ICF.
  3. Have histologically confirmed NMIBC CIS via biopsy with/without resected papillarydisease (Ta, T1) (high grade) using the 2004 World Health Organization ("WHO") /International Society of Urologic Pathology classification system. The most recentcystoscopy / TURBT must have been performed within 12 weeks of the Study Treatmentdate to confirm: histology, grade and stage.
  4. Intolerant to BCG or considered BCG-Unresponsive, which is at least one of thefollowing:
  • At least five of six doses of an initial induction course, plus at least two ofthree doses of maintenance therapy, or
  • At least five of six doses of an initial induction course, plus at least two ofsix doses of a second induction course.
  1. Are not candidates for cystectomy on medical grounds or refuse radical cystectomy.
  2. Have an Eastern Cooperative Oncology Group ("ECOG") performance score of 0 to 2.
  3. Have satisfactory bladder function. Ability to retain Study Drug for a minimum of 60minutes.
  4. Are available for the duration of the Study including follow-up (approximately 15months).
  5. Female patients of childbearing potential must have a negative Human ChorionicGonadotropin ("HCG") pregnancy test taken during the screening visit and confirmedprior to the Study Treatment.
  6. Female patients of childbearing potential must be willing to use 2 methods of birthcontrol (i.e.: oral contraceptive, pills, diaphragm or condoms) or be surgicallysterile, or abstain from heterosexual activity for two weeks after the StudyTreatment. Patients of childbearing potential are those who have not been surgicallysterilized or have not been free from menses for >1 year.

Exclusion

Exclusion Criteria:

  1. Past or current muscle invasive (i.e.: T2, T3, T4) or metastatic urothelial carcinoma.
  2. Has concurrent extravesical (i.e.: urethra, ureter, renal pelvis, prostate orprostatic ducts) non-muscle invasive transitional cell carcinoma of the urothelium. (confirmed by staging to exclude extravesical disease, which may include radiologicalimaging and/or biopsy) within 3 months of enrollment: If previous work up occurred more than 3 months prior to enrollment, staging forextravesical disease must be repeated prior to enrolment in order to determineeligibility.
  3. Active gross hematuria.
  4. Have a known additional malignancy that is progressing or requires active treatment.Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of theskin that has undergone potentially curative therapy, in situ cervical cancer orlocalized prostate cancer under active surveillance with Gleason 6 disease. A historyof prostate cancer that was treated with definitive intent (surgically or throughradiation therapy) is acceptable, provided that the following criteria are met: StageT2N0M0 or lower Prostate-Specific Antigen ("PSA") undetectable for 2 years while offandrogen deprivation therapy or no more than 2 consecutive rising PSAs.
  5. Have a history or current evidence of any condition, therapy, surgery or laboratoryabnormality that, in the opinion of the PI, might confound the results of the Study,interfere with the patient's participation in the Study, or is not in the bestinterest of the patient to participate.
  6. Currently receiving treatment with a prohibited concomitant therapy (refer to 12.2.1,Prohibited Medications).
  7. Participated in a study with an investigational agent or device within 1 month fromthe first dose of current Study treatment.
  8. Prior treatment with an intravesical chemotherapeutic agent within 1 month of thefirst dose of current Study Drug, with the exception of a single perioperative dose ofchemotherapy immediately post-TURBT (not considered treatment).
  9. Have an active infection requiring systemic therapy, including active or intractableUrinary Tract Infection ("UTI"), not resolved prior to the procedure.
  10. Has any contraindication to general or spinal anesthesia.
  11. Is pregnant or breastfeeding within the projected duration of Study II, starting withthe screening visit through to two weeks following the second Ruvidar® (TLD-1433)instillation.

Study Design

Total Participants: 125
Treatment Group(s): 1
Primary Treatment: Ruvidar® (TLD-1433) Bladder infusion and PDT
Phase: 2
Study Start date:
August 30, 2019
Estimated Completion Date:
December 31, 2025

Study Description

  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.

Connect with a study center

  • Site 01-005 - The Vancouver Prostate Centre - Diamond Health Care Centre - Vancouver General Hospital

    Vancouver, British Columbia V5Z 1M9
    Canada

    Active - Recruiting

  • Site 01-004 - Nova Scotia Health Authority - Centre for Applied Urology Research

    Halifax, Nova Scotia B3H 2Y9
    Canada

    Active - Recruiting

  • Site 01-002- London Health Sciences Centre - Victoria Hospital

    London, Ontario N6A 5W9
    Canada

    Active - Recruiting

  • Site 01-001 - University Health Network - Princess Margaret Cancer Centre

    Toronto, Ontario M5G 2C4
    Canada

    Active - Recruiting

  • Site 01-003 - McGill University Health Centre - Glen-Cedars Cancer Centre

    Montréal, Quebec H4A 3J1
    Canada

    Active - Recruiting

  • Site 02-012 - University of Chicago

    Chicago, Illinois 60637
    United States

    Active - Recruiting

  • Site 02-008 - MidLantic Urology

    Bala-Cynwyd, Pennsylvania 19087
    United States

    Active - Recruiting

  • Site 02-006 - Carolina Urologic Research Center

    Myrtle Beach, South Carolina 29572
    United States

    Active - Recruiting

  • Site 02-007 - Urology Associates, P. C

    Nashville, Tennessee 37209
    United States

    Active - Recruiting

  • Site 02-010 - Urology San Antonio P. A

    San Antonio, Texas 78229
    United States

    Active - Recruiting

  • Site 02-009 - Virginia Urology

    Richmond, Virginia 23235
    United States

    Terminated

  • Site 02-011 - University of Wisconsin Health University Hospital

    Madison, Wisconsin 53792
    United States

    Active - Recruiting

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