This phase I/II trial studies the side effects and best dose of gemcitabine when given together with BCG vaccine and to see how well they work in treating patients with high-grade non-muscle invasive bladder cancer that has come back after previous BCG treatment (BCG-relapsing). Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. BCG vaccine may help the body build an effective immune response to kill tumor cells. Re-treatment with BCG in combination with gemcitabine may be an effective way to treat patients with BCG-relapsing high-grade non-muscle invasive bladder cancer.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT04179162.
PRIMARY OBJECTIVES:
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)
SECONDARY OBJECTIVES:
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)
EXPLORATORY OBJECTIVES:
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 on weeks 2, 3, 5, 6, 8 and 9. Treatment continues in the absence of disease progression or unacceptable toxicity.
Lead OrganizationMemorial Sloan Kettering Cancer Center
Principal InvestigatorEugene J Pietzak
