Phase I/II Trial of Bacillus Calmette-Guérin (BCG) and Intravesical Gemcitabine for Patients With BCG-Relapsing High-Grade Non-Muscle Invasive Bladder Cancer
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 54
- 试验地点
- 16
- 主要终点
- evaluate the MTD (Phase I)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Bacillus Calmette-Guérin (BCG) and Gemcitabine
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.
干预措施: Gemcitabine (Drug)
Bacillus Calmette-Guérin (BCG) and Gemcitabine
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.
干预措施: Bacillus Calmette-Guérin (BCG) (Drug)
结局指标
主要结局
evaluate the MTD (Phase I)
时间窗: 1 year
Describe the toxicities by frequency and by grade.This study will use CTCAE version 5.0 for toxicity and serious adverse event reporting.
proportion of patients who are disease free
时间窗: 6 months after the start of treatment
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).
次要结局
未报告次要终点