Clinical trial NCT04179162: Bacillus Calmette-Guérin (BCG) and Gemcitabine in People With High-Grade Non-Muscle Invasive Bladder Cancer That Came Back After BCG Treatment
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Non-Muscle Invasive Bladder Cancer (NMIBC)
Keywords: Bacillus Calmette-Guérin (BCG)
Gemcitabine
19-374
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
First posted: 2019-11-27
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention 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).
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: evaluate the MTD (Phase I)
timeFrame: 1 year
measure: proportion of patients who are disease free
timeFrame: 6 months after the start of treatment
Secondary outcomes:
Other outcomes:
Locations:
city: Hartford
country: United States
facility: Hartford Healthcare (Data Collection)
state: Connecticut
city: Basking Ridge
country: United States
facility: Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)
state: New Jersey
city: Middletown
country: United States
facility: Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
state: New Jersey
city: Montvale
country: United States
facility: Memorial Sloan Kettering Bergen (Limited Protocol Activities)
state: New Jersey
city: Commack
country: United States
facility: Memorial Sloan Kettering Commack (Limited Protocol Activities)
state: New York
city: Harrison
country: United States
facility: Memorial Sloan Kettering Westchester (Limited Protocol Activities)
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center (All Protocol Activities)
state: New York
city: Uniondale
country: United States
facility: Memorial Sloan Kettering Nassau (Limited Protocol Activities)
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Eugene Pietzak, MD
role: PRINCIPAL_INVESTIGATOR
References: