Bacillus Calmette-Guérin (BCG) and Gemcitabine in People With High-Grade Non-Muscle Invasive Bladder Cancer That Came Back After BCG Treatment

Study Overview
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Brief Summary
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This study will test the safety of BCG and gemcitabine in people who have BCG-relapsing Non-Muscle Invasive Bladder Cancer (NMIBC). The researchers will test increasing doses of gemcitabine to find the highest dose that causes few or mild side effects when combined with BCG. The study will also look at whether this combination of drugs is effective in treating BCG-relapsing NMIBC.

Official Title
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Phase I/II Trial of Bacillus Calmette-Guérin (BCG) and Intravesical Gemcitabine for Patients With BCG-Relapsing High-Grade Non-Muscle Invasive Bladder Cancer

Conditions
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Non-Muscle Invasive Bladder Cancer (NMIBC)

Intervention / Treatment
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* Drug: Bacillus Calmette-Guérin (BCG)
* Drug: Gemcitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Recurrent for persistent high-grade NMIBC Ta/T1/Tis (Ta/T1 with CIS is preferred, but not required) within 24 months of the last treatment with BCG (with or without IFN) o Up to 26 months from the last BCG treatment is allowed for the treating physician to perform a transurethral resection of bladder tumor (TURBT) so long as there is evidence of recurrent disease (by positive cytology, imaging, or office cystoscopy) within 24 months of last BCG transurethral resection of bladder tumor (TURBT) Pathologic confirmation of stage, grade, and urothelial histology by the Department of Pathology at 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 Age ≥18 years Karnofsky performance status ≥60% Informed consent Exclusion Criteria: 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 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: This is a phase I/II trial of intravesical gemcitabine given between doses of BCG in patients who have relapsing but BCG-responsiveNon-Muscle Invasive Bladder Cancer (NMIBC).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bacillus Calmette-Guérin (BCG) and Gemcitabine<br>Eligible patients will receive combination intravesical chemoimmunotherapy. Treatment is sequential, with twice-weekly intravesical gemcitabine given at weeks 1, 4, 7, and 10, for a total of 8 doses, administered in a standard fashion. In phase I, the dose of gemcitabine will depend on the dose level being assessed for the determination of the MTD. phase II, 1 dose level will be given (the MTD from phase I). Fixed doses of once-weekly intravesical BCG therapy (TICE strain, 50 mg) will be given at weeks 2 (+/- 2 days), 3 (+/- 2 days), 5 (+/- 2 days), 6 (+/- 2 days), 8 (+/- 2 days), and 9 (+/- 2 days), for a total of 6 doses, also administered in a standard fashion. All intravesical therapy will be administered in the chemotherapy suite on an outpatient basis, in accordance with standard clinical practice. Intravesical therapies will be retained in the bladder for up to 2 h (BCG) or 1 h (gemcitabine), or as tolerated. | Drug: Bacillus Calmette-Guérin (BCG)<br>* Patients will receive once-weekly intravesical BCG therapy (TICE strain, 50 mg) at weeks 2 (+/- 2 days), 3 (+/- 2 days), 5 (+/- 2 days), 6(+/- 2 days), 8 (+/- 2 days), and 9 (+/- 2 days).<br>Drug: Gemcitabine<br>* Patients will receive gemcitabine at their specified dose level, given in a twice weekly fashion, with 72 to 96 h (+/- 1 day) between doses, at weeks 1, 4, 7, and 10.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| evaluate the MTD (Phase I) | Describe the toxicities by frequency and by grade.This study will use CTCAE version 5.0 for toxicity and serious adverse event reporting. | 1 year | 
| proportion of patients who are disease free | Will be assessed by both urine cytology and cystoscopy at 6 months after initiation of therapy. Disease free (i.e., complete treatment response) is defined as no evidence of disease (negative cytology and cystoscopy). | 6 months after the start of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bacillus Calmette-Guérin (BCG), Gemcitabine, 19-374