Bladder (Urothelial, Transitional Cell) Cancer, NMIBC, Non-Muscle Invasive Bladder Urothelial Carcinoma, Urothelial Carcinoma Bladder
Conditions
Keywords
BCG, NMIBC, Gemcitabine, Tumor Immune MicroEnvironment, Systemic immunity, Mucosal immune response, Immune Biomarker
Brief summary
This study is being conducted to establish a novel tumor tissue- and blood-based biomarker test to assess early systemic and local response to immunomodulation by BCG immunotherapy in patients with high-risk non-muscle invasive bladder cancer. Responses will be compared between patients with high-risk NMIBC who are being treated with standard of care BCG therapy and those treated with combination chemotherapy. Local and systemic immune monitoring assays will allow early identification of patients who will not benefit from BCG immunotherapy.
Detailed description
BCG immunotherapy is the current gold standard for NMIBC. However, \ 50% of patients will eventually experience recurrence or progression. Pre-treatment immune competence of the patient, the bladder microenvironment and systemic immune responses to immunomodulation by BCG govern effectiveness. The investigators intend to utilize a novel tumor tissue and blood based biomarker test to assess early systemic responses to standard of care BCG based immunotherapy as well as alternate strategies to enhance immune responses as measured systemically as well as based on early response rates (3 month complete response or 3 month recurrence). The goal of this study is to develop strategies to identify novel more effective anti-tumor immune responses for NMIBC.
Interventions
DRUGGemcitabine + BCG
Patients will receive a single intravesical instillation of gemcitabine (2000 mg) at week 0 followed by weekly BCG (50 mg of TICE strain) for a total of 5 instillations. Biopsy will be conducted within three months of completing the induction phase.
DRUGBCG (TICE strain)
Patients will receive intravesical BCG (50 mg, TICE strain) at weekly intervals for a total of 6 instillations. Biopsy will be performed within 3 months of completing the induction phase.
Sponsors
Queen's University, Kingston, Ontario
Queen's University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with an initial diagnosis of NMIBC without previous exposure to BCG immunotherapy (BCG-naive). * Patients with pathologic diagnosis of Ta or T1 high grade NMIBC with or without CIS. * Participants older than 65 years of age.
Exclusion criteria
* Patients with prior exposure to BCG immunotherapy. * Immunosuppressed patients on steroids, transplants etc.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| BCG ImmunoScore | 3 months | Complete response at 3 months with no evidence of tumor recurrence as assessed by biopsy. Demonstrable immunological responses measured at weeks 2, and 5 post-treatment, based on a novel tissue and blood based immune biomarker. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Recurrence free survival | 12 months | Recurrence free survival at 12 months post treatment initiation. |
Countries
Canada
Contacts
Primary ContactDavid Robert Siemens, MD
Outcome results
None listed