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

Non-Muscle Invasive Bladder Cancer (NMIBC) Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04179162
• Other study ID #: 19-374
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: November 22, 2019
• Est. completion date: November 2025

Study information

• Verified date: March 2024
• Source: Memorial Sloan Kettering Cancer Center
• Contact: Eugene Pietzak, MD
• Phone: 646-422-4781
• Email: pietzake[@]mskcc.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 68
• Est. completion date: November 2025
• Est. primary completion date: November 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Non-Muscle Invasive Bladder Cancer (NMIBC)
• Urinary Bladder Neoplasms

Intervention

Drug:
• Bacillus Calmette-Guérin (BCG)
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).
• Gemcitabine
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.

Locations

Country	Name	City	State
United States	Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)	Basking Ridge	New Jersey
United States	Memorial Sloan Kettering Commack (Limited Protocol Activities)	Commack	New York
United States	Memorial Sloan Kettering Westchester (Limited Protocol Activities)	Harrison	New York
United States	Hartford Healthcare (Data Collection)	Hartford	Connecticut
United States	Memorial Sloan Kettering Monmouth (Limited Protocol Activities)	Middletown	New Jersey
United States	Memorial Sloan Kettering Bergen (Limited Protocol Activities)	Montvale	New Jersey
United States	Memorial Sloan Kettering Cancer Center (All Protocol Activities)	New York	New York
United States	Memorial Sloan Kettering Nassau (Limited Protocol Activities)	Uniondale	New York

Sponsors (1)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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

External Links

•   Memorial Sloan Kettering Cancer Center