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

NCT03945162 | Recruiting Phase 2 DMC FDA Drug FDA Device

• 1 other identifier: Ruvidar® (TLD-1433) NMIBC PDT
• Study Type: interventional
• Target: 90
• Locations: 2 countries
• Sites: 16

Brief Summary

This is a phase II, open-label, single-arm, multi-center Study conducted in Canada and the United States. Patients with Non-Muscle Invasive Bladder Cancer ("NMIBC") Carcinoma In-Situ ("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 90 patients who will undergo one (1) Study Procedure, with up to two (2) additional re-induction Study Procedures based on patient response.

Conditions

Non-Muscle Invasive Bladder Cancer ("NMIBC") Unresponsive/Intolerant to BCG

Keywords

Photodynamic Therapy; Non-muscle invasive bladder cancer ("NMIBC"); Urothelial carcinoma; Ta bladder cancer; T1 bladder cancer; Unresponsive/Intolerant to BCG

Outcome Measures

Primary Outcomes (1)

• Efficacy, evaluated by Complete Response ("CR").

  The primary endpoint of Study II is efficacy, evaluated by the Complete Response ("CR") at any time point in patients with Carcinoma In-Situ ("CIS") with resected papillary disease. Patient CR is defined as at least one of the following: * Negative cystoscopy and negative (including atypical) urine cytology * Positive cystoscopy with biopsy-proven benign or low-grade NMIBC and negative cytology * Negative cystoscopy with malignant urine cytology, if urothelial cancer is suspected in the upper tract or prostatic urethra and random bladder biopsies are negative.

  Throughout Study II and up to the completion of the follow-up phase (15 month)

Secondary Outcomes (2)

• Efficacy, evaluated by the duration of CR

  Throughout Study II and up to the completion of the follow-up phase (15 month)

• Three year patient assessments, for observation only.

  Follow-up phase from 15 to 36 months for those who remain in Study.

Other Outcomes (1)

• Safety, evaluated by the incidence and severity of Adverse Events.

  Throughout the study and up to the completion of the follow-up phase (15 month)

Study Arms (1)

0.70 mg/cm^2 Ruvidar® (TLD-1433) Bladder instillation and Photodynamic Therapy

EXPERIMENTAL

Each Study Procedure is a single instillation of Ruvidar® (TLD-1433) (at the therapeutic dose of 0.70 mg/cm\^2) will be infused intravesically into the bladder for approximately 60 minutes, followed by PDT treatment using the TLC-3200 system, which is performed after Ruvidar® (TLD-1433) has been rinsed from the bladder. One Study Procedure will be performed, with up to 2 additional re-induction Study Procedures based on patient response.

Combination Product: Ruvidar® (TLD-1433) bladder infusion and PDT

Interventions

Ruvidar® (TLD-1433) bladder infusion and PDT COMBINATION_PRODUCT

Ruvidar® (TLD-1433) is infused into the bladder and treatment of bladder wall with PDT light activation using the TLC-3200 system.

0.70 mg/cm^2 Ruvidar® (TLD-1433) Bladder instillation and Photodynamic Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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, or
• At 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Theralase® Technologies Inc.: lead

Study Sites (16)

Site 02-012 - University of Chicago

Chicago, Illinois, 60637, United States

RECRUITING

Site 02-016 - Urology of Indiana

Greenwood, Indiana, 46143, United States

RECRUITING

Site 02-015 - Associated Medical Professionals of New York

Syracuse, New York, 13210, United States

RECRUITING

Site 02-017 - Central Ohio Urology Group

Gahanna, Ohio, 43230, United States

RECRUITING

Site 02-008 - MidLantic Urology

Bala-Cynwyd, Pennsylvania, 19004, United States

TERMINATED

Site 02-006 - Carolina Urologic Research Center

Myrtle Beach, South Carolina, 29572, United States

RECRUITING

Site 02-007 - Urology Associates, P. C

Nashville, Tennessee, 37209, United States

RECRUITING

Site 02-010 - Urology San Antonio P. A

San Antonio, Texas, 78229, United States

TERMINATED

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

RECRUITING

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

Vancouver, British Columbia, V5Z 1M9, Canada

RECRUITING

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

Halifax, Nova Scotia, B3H 2Y9, Canada

RECRUITING

Site 01-014 - St. Joseph's Healthcare

Hamilton, Ontario, L8N 4A6, Canada

RECRUITING

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

London, Ontario, N6A 5W9, Canada

RECRUITING

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

Toronto, Ontario, M5G 2C4, Canada

RECRUITING

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

Montreal, Quebec, H4A 3J1, Canada

RECRUITING

MeSH Terms

Conditions

Non-Muscle Invasive Bladder Neoplasms; Carcinoma, Transitional Cell

Interventions

1-phenyl-3,3-dimethyltriazene

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urinary Bladder Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Study Officials

• Girish Kulkarni, MD, FRCSC

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Arkady Mandel, MD, PhD, DSc

CONTACT

416-699-5273; amandel@theralase.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2019
• First Posted: May 10, 2019
• Study Start: August 30, 2019
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: November 24, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (10); CA (6)