Recruiting
Phase 2
Intravesical Photodynamic Therapy ("PDT") in BCG-Unresponsive/Intolerant Non-Muscle Invasive Bladder Cancer ("NMIBC") Patients
Condition(s) studied
Non-Muscle Invasive Bladder Cancer ("NMIBC") Unresponsive/Intolerant to BCG
Investigational drug(s) / intervention(s)
Ruvidar® (TLD-1433) bladder infusion and PDT
Ruvidar® (TLD-1433) bladder infusion and PDT: Ruvidar® (TLD-1433) is infused into the bladder and treatment of bladder wall with PDT light activation using the TLC-3200 system.
Study 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.
Eligibility
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 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.
4. 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.
5. Are not candidates for cystectomy on medical grounds or refuse radical cystectomy.
6. Have an Eastern Cooperative Oncology Group ("ECOG") performance score of 0 to 2.
7. Have satisfactory bladder function. Ability to retain Study Drug for a minimum of 60 minutes.
8. Are available for the duration of the Study including follow-up (approximately 15 months).
9. 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.
10. 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:
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 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.
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 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.
5. 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.
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 from the first dose of current Study Procedure.
8. 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).
9. Have an active infection requiring systemic therapy, including active or intractable Urinary 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 with the screening visit through to two weeks following the last Study Procedure.
Primary outcome measure(s)
- Efficacy, evaluated by Complete Response ("CR"). — Throughout Study II and up to the completion of the follow-up phase (15 month)
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.
Trial sites (16)
| Facility | City | Region | Status |
| Site 02-012 - University of Chicago |
Chicago |
Illinois |
Recruiting |
| Site 02-016 - Urology of Indiana |
Greenwood |
Indiana |
Recruiting |
| Site 02-015 - Associated Medical Professionals of New York |
Syracuse |
New York |
Recruiting |
| Site 02-017 - Central Ohio Urology Group |
Gahanna |
Ohio |
Recruiting |
| Site 02-008 - MidLantic Urology |
Bala-Cynwyd |
Pennsylvania |
Terminated |
| Site 02-006 - Carolina Urologic Research Center |
Myrtle Beach |
South Carolina |
Recruiting |
| Site 02-007 - Urology Associates, P. C |
Nashville |
Tennessee |
Recruiting |
| Site 02-010 - Urology San Antonio P. A |
San Antonio |
Texas |
Terminated |
| Site 02-009 - Virginia Urology |
Richmond |
Virginia |
Terminated |
| Site 02-011 - University of Wisconsin Health University Hospital |
Madison |
Wisconsin |
Recruiting |
| Site 01-005 - The Vancouver Prostate Centre - Diamond Health Care Centre - Vancouver General Hospital |
Vancouver |
British Columbia |
Recruiting |
| Site 01-004 - Nova Scotia Health Authority - Centre for Applied Urology Research |
Halifax |
Nova Scotia |
Recruiting |
| Site 01-014 - St. Joseph's Healthcare |
Hamilton |
Ontario |
Recruiting |
| Site 01-002- London Health Sciences Centre - Victoria Hospital |
London |
Ontario |
Recruiting |
| Site 01-001 - University Health Network - Princess Margaret Cancer Centre |
Toronto |
Ontario |
Recruiting |
| Site 01-003 - McGill University Health Centre - Glen-Cedars Cancer Centre |
Montreal |
Quebec |
Recruiting |