A Phase II Clinical Study of Intravesical Ruvidar® in Patients With BCG-Unresponsive Non-Muscle Invasive Bladder Cancer ("NMIBC") Carcinoma In-Situ ("CIS") or Patients Who Are Intolerant to BCG Therapy ("Study II")

Study Identifier:
TLD-1433-2
CT.gov Identifier:
NCT03945162
EudraCT Identifier:
N/A
EU Trial (CTIS) Number:
N/A
Study Contact Information:
N/A
Recruitment Complete

Considering participating in a START clinical trial?

Get Started

Study Summary

To evaluate efficacy of TLD-1433 in patients with non-muscle invasive bladder cancer. To study intravesical photodynamic therapy in patients with BCG-unresponsive non-muscle invasive bladder cancer ("NMIBC") or patients who are intolerant to BCG therapy. To discover if the TLD-1433 (“Study Drug”) combined with TLC-3200 (“Study Device”) (collectively the “Study Treatment”) are effective in the destruction of Bacillus Calmette-Guérin (“BCG”)-Unresponsive Non-Muscle Invasive Bladder Cancer (“NMIBC”).

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
  • Bladder
    • Phase
    The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
    II
    Sex
    Female & Male
    Age
    18+ years
    Study Drug
  • Drug: Participant Group/Arm:
    • Read More
  • Drug: Treatment and follow-up of 100 patients providing them two Theralase PDT treatments, one at Day 0 and one at Day 180. Experimental: 0.7 mg/cm^2 TLD-1433 Bladder infusion and Photodynamic Therapy A single instillation of TLD-1433 (at the therapeutic dose of 0.7 mg/cm^2) will be infused intravesically into the bladder for approximately 60 minutes. Photodynamic therapy treatment is performed after TLD1433 has been rinsed from the bladder. Two treatment procedures will be performed, a primary treatment at Day 0 and a secondary treatment at Day 180 post primary treatment. Combination Product: TLD-1433 Bladder infusion and Photodynamic Therapy TLD1433 is infused into the bladder, followed by repeated rinsing and treatment of bladder wall with photodynamic therapy (PDT). 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. 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. Key patient withdrawal criteria of NMIBC progression, which includes Progression to Muscle Invasive Bladder Cancer (MIBC”)” and Progression to metastatic disease”. Patients treated with two Study Treatments (Day 0 and Day 180) consisting of an intravesical instillation of the photosensitizer TLD-1433 (0.70 mg/cm2) followed by activation with a 520 nm intravesical laser under general anesthesia (Study Device TLC-3200) to a total of 90 J/cm2 of laser light
    • Study Status
    Indicates the current recruitment status or the expanded access status
    Recruitment Complete

    Requirements information
    Inclusion criteria
    • Be willing and able to provide a written Informed Consent Form ("ICF") for the Study.Be > 18 years of age on day of signing ICF.Have histologically confirmed NMIBC CIS via biopsy with/without resected papillary disease (Ta, T1) (high grade) using the 2004 World Health Organization ("WHO") / International Society of Urologic Pathology classification system. The most recent cystoscopy / TURBT must have been performed within 12 weeks of the Study Procedure date to confirm: histology, grade and stage.Intolerant to BCG or considered BCG-Unresponsive, which 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, orAt least five of six doses of an initial induction course, plus at least two of six doses of a second induction course.Are not candidates for cystectomy on medical grounds or refuse radical cystectomy.Have an Eastern Cooperative Oncology Group ("ECOG") performance score of 0 to 2.Have satisfactory bladder function. Ability to retain Study Drug for a minimum of 60 minutes.Are available for the duration of the Study including follow-up (approximately 15 months).Female patients of childbearing potential must have a negative Human Chorionic Gonadotropin ("HCG") pregnancy test taken during the screening visit and confirmed prior to the Study Procedure.Female patients of childbearing potential must be willing to use 2 methods of birth control (i.e.: oral contraceptive, pills, diaphragm or condoms) or be surgically sterile, or abstain from heterosexual activity for two weeks after the Study Procedure. Patients of childbearing potential are those who have not been surgically sterilized or have not been free from menses for >1 year.
    Exclusion criteria
    • Past or current muscle invasive (i.e.: T2, T3, T4) or metastatic urothelial carcinoma.Has concurrent extravesical (i.e.: urethra, ureter, renal pelvis, prostate or prostatic ducts) non-muscle invasive transitional cell carcinoma of the urothelium. (confirmed by staging to exclude extravesical disease, which may include radiological imaging and/or biopsy) within 3 months of enrollment:If previous work up occurred more than 3 months prior to enrollment, staging for extravesical disease must be repeated prior to enrolment in order to determine eligibility.Active gross hematuria.Have a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, in situ cervical cancer or localized prostate cancer under active surveillance with Gleason 6 disease. A history of prostate cancer that was treated with definitive intent (surgically or through radiation therapy) is acceptable, provided that the following criteria are met: Stage T2N0M0 or lower Prostate-Specific Antigen ("PSA") undetectable for 2 years while off androgen deprivation therapy or no more than 2 consecutive rising PSAs.Have a history or current evidence of any condition, therapy, surgery or laboratory abnormality 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 best interest of the patient to participate.Currently receiving treatment with a prohibited concomitant therapy (refer to 12.2.1, Prohibited Medications).Participated in a study with an investigational agent or device within 1 month from the first dose of current Study Procedure.Prior treatment with an intravesical chemotherapeutic agent within 1 month of the first dose of current Study Drug, with the exception of a single perioperative dose of chemotherapy immediately post-TURBT (not considered treatment).Have an active infection requiring systemic therapy, including active or intractable Urinary Tract Infection ("UTI"), not resolved prior to the procedure.Has any contraindication to general or spinal anesthesia.Is pregnant or breastfeeding within the projected duration of Study II, starting with the screening visit through to two weeks following the last Study Procedure.

    Clinical Study Information for Healthcare Providers

    By clicking the button below you will find in-depth information about this clinical trial, including study design, primary and secondary endpoints, and more. This information is intended for healthcare professionals seeking to review the scientific and operational aspects of the study.

    View Study Information

    Study Locations

    Location
    Investigator
    Status
    Condition(s) Treated at Site
    Location
    START Carolinas
    Myrtle Beach, SC, United States, 29572
    Investigator
    Neal Shore
    Status
    Recruiting
    Condition(s) Treated at Site
    Bladder