Bacillus Calmette-Guerin (BCG) Vaccine and Gemcitabine for the Treatment of BCG-Relapsing High-Grade Non-Muscle Invasive Bladder Cancer
- Recurrent high-grade NMIBC (Tis, Ta high grade [TaHG], or T1) within 24 months of the last treatment with BCG (with or without interferon [IFN])
- Pathologic confirmation of stage, grade, and urothelial histology by the Department of Pathology at Memorial Sloan Kettering (MSK)
- All visible papillary lesions macroscopically resected within 60 days of treatment initiation
- Absence of urothelial carcinoma involving the upper urinary tract (documented by radiological imaging or ureteroscopy) within 12 months from the start of treatment
- Receipt of restaging transurethral resection (TUR) for any tumor with invasion into the lamina propria (HGT1) as part of standard care
- Karnofsky performance status >= 60%
- Informed consent
- Positive pregnancy test
- Known contraindications to BCG * History of systemic hypersensitivity reaction or history of febrile systemic BCG reaction * Febrile illness or persistent gross hematuria * Active tuberculosis * Immunosuppression due to congenital or acquired immune deficiency, concurrent immune suppressive disease, systemic cancer therapy, or chronic immunosuppressive therapy other than topical or inhaled corticosteroids
- History of or currently being treated for muscle-invasive (i.e., stage T2 or higher) or metastatic urothelial cell carcinoma
- Evidence of concurrent extravesical (i.e., urethra, ureter, or renal pelvis) urothelial cell carcinoma
- BCG-unresponsive NMIBC as defined by the Food and Drug Administration (FDA): * HGT1 within 3 months after an induction BCG course (received >= 5 of 6 doses) * Persistent or recurrent high-grade NMIBC (Tis, Ta, T1) within 6 months of >= 5 of 6 doses of induction BCG therapy and >= 2 of 3 doses of maintenance BCG therapy
I. To determine the maximum tolerated dose (MTD) for the combination of intravesical Bacillus Calmette-Guerin (BCG) and intravesical gemcitabine in patients with relapsing but BCG-responsive non-muscle invasive bladder cancer (NMIBC). (Phase I)
II. To determine the therapeutic complete response rate to combination intravesical gemcitabine and intravesical BCG, which is defined as the proportion of patients who are disease free at 6 months after the start of treatment. (Phase II)
I. To determine the proportion of patients who are recurrence free at 12 months after starting combination intravesical gemcitabine and intravesical BCG. (Phase II)
II. To determine the proportion of patients who are progression free at 12 months after starting combination intravesical gemcitabine and intravesical BCG (progression is defined as the development of muscle-invasive disease [>= T2] or metastasis). (Phase II)
III. To determine the proportion of patients who are free from radical treatment (cystectomy or radiation) at 12 months after starting combination intravesical gemcitabine and intravesical BCG. (Phase II)
I. To determine whether changes in immune cell populations within the tumor microenvironment (TME) are associated with response to combination intravesical chemoimmunotherapy.
II. To define molecular determinants of response and resistance to combination intravesical chemoimmunotherapy.
OUTLINE: This is a phase I, dose-escalation study of gemcitabine followed by a phase II study.
Patients receive gemcitabine intravesically twice a week at weeks 1, 4, 7, and 10 for 8 doses. Patients also receive BCG vaccine intravesically once per week at weeks 2, 3, 5, 6, 8, and 9 for 6 doses. Treatment continues in the absence of disease progression or unacceptable toxicity.
Trial Phase Phase I/II
Trial Type Treatment
Memorial Sloan Kettering Cancer Center
Eugene J Pietzak
- Primary ID 19-374
- Secondary IDs NCI-2019-08319
- Clinicaltrials.gov ID NCT04179162