A Phase 3, Randomized, Active-Controlled, Open-Label, Multicenter Study To Evaluate The Efficacy And Safety Of EN3348 (MCC) as Compared With Mitomycin C In The Intravesical Treatment Of Subjects With BCG Recurrent Or Refractory Non-Muscle Invasive Bladder Cancer
试验速览
- 阶段
- 3 期
- 状态
- Other
- 入组人数
- 450
- 试验地点
- 11
- 主要终点
- The primary objective of this study is to evaluate the efficacy of EN3348 as compared with mitomycin C in the treatment of subjects with BCG recurrent or refractory NMIBC
研究概览
简要总结
This is a phase 3 randomized, active-controlled, open-label, multicenter study that will be conducted in approximately 120 investigational sites worldwide. Subjects with either BCG recurrent or refractory NMIBC (Ta high grade, T1 low or high grade, CIS) will be eligible for participation in this study. Refractory disease is defined as failure to achieve tumor-free status by 6 months of initiation of adequate BCG therapy (minimum of 5 weekly doses of BCG (induction) followed by a second course (induction or maintenance) in which subject received a minimum of 2 doses).xml:namespace prefix = o ns = "urn:schemas-microsoft-com:office:office" /
Recurrent disease is defined as reappearance of disease after achieving a tumor-free status by 6 months after initiation of adequate BCG therapy. Subjects with recurrent disease must have recurred within 18 months following the last dose of BCG.
Approximately 450 subjects will be randomized. The randomization will be 1:1 and stratified by geographic region (North America, xml:namespace prefix = st1 ns = "urn:schemas-microsoft-com:office:smarttags" /India, Europe), tumor pathology (CIS versus no CIS), prior BCG response (refractory versus recurrent), and prior intravesical (IVe) chemotherapy (yes/no).
The study will consists of 4 phases: Screening phase of 6 weeks, induction phase of 6 weeks, maintenance phase of 10 months and follow up phase of up to approximately 24 months.
研究设计
- 研究类型
- Interventional
- 分配方式
- Stratified randomization
- 盲法
- Not Applicable
入排标准
- 年龄范围
- 18.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •Subjects are eligible for inclusion into the study if the following criteria are met:
- •Males and females who are 18 years of age or older at time of consent signing
- •Have either BCG recurrent or refractory NMIBC: a.
- •Refractory disease is defined as evidence of persistent high grade bladder cancer (Ta HG, T1 and/or CIS) at least 6 months from the start of full induction course of BCG1 with or without maintenance/ re-treatment at 3 months.
- •Recurrent disease is defined as reappearance of disease after achieving a tumor-free status by 6 months following a full induction course of BCG1 with or without maintenance/ re-treatment at 3 months.
- •Subjects with recurrent disease must have recurred within 18 months following the last dose of BCG.
- •1 A full induction course of BCG is defined as at least 5 out of 6 total expected instillations of BCG within a period of 2 months, regardless of dose strength.
- •Have histologically confirmed NMIBC (according to 2004 WHO classification) within 8 weeks prior to randomization: a.
- •High grade Ta papillary lesion(s) b.
- •CIS, with or without Ta or T1 papillary tumor(s) of any grade
- •Have had all visible papillary and resectable CIS lesion(s) removed by TURBT within 8 weeks prior to randomization
- •Available for the duration of the study including follow-up (approximately 36 months)
- •Have an Eastern Cooperative Oncology Group (ECOG) performance status grade of 2 or less
- •Have no evidence of urothelial carcinoma involving the upper urinary tract or the urethra (confirmed by extravesical work up, which may include radiological imaging and/or biopsy) within 6 months prior to randomization: a.
- •If previous work up occurred more than 6 months prior to randomization, extravesical work up must be repeated prior to randomization in order to determine eligibility
- •Subjects (male and female) of child-bearing potential (including female subjects who are post-menopausal for less than 1 year) must be willing to practice effective contraception (as defined by the Investigator) during the study and be willing and able to continue contraception for 30 days after their last dose of study treatment.
- •Is able to understand and give written informed consent.
排除标准
- •Subjects meeting the following criteria will be excluded from participation in the study:
- •Current or previous history of muscle invasive bladder tumors
- •Current or previous history of positive lymph nodes and/or metastatic bladder cancer
- •Current evidence of pure squamous cell carcinoma, pure adenocarcinoma or pure undifferentiated carcinoma of the bladder
- •Currently receiving systemic anti-cancer therapy (cytotoxic/cytostatic or immunotherapy)
- •Currently receiving treatment with a prohibited therapy .
- •Current or prior history of systemic lupus erythematosus
- •Systemic immunotherapy within 6 months of randomization
- •Treatment with an investigational agent within 30 days or 5 half lives from randomization, whichever is longer
- •Prior treatment with an intravesical chemotherapeutic agent within 3 months of randomization, except for single perioperative dose of chemotherapy immediately post-TURBT
- •Prior treatment with EN3348 (MCC) or any other mycobacterial cell wall composition or formulation
- •Refractory to Mitomycin C (failure to achieve tumor-free status following minimum of a 6-week induction course of mitomycin C)
- •Contraindication to mitomycin C
- •Untreated urinary tract or bladder infection
- •ANC 1000/µL and hemoglobin 10 g/dL
- •Known cardiovascular disease such as myocardial infarction within the past 3 months, unstable angina pectoris, congestive heart failure (New York Heart Association [NYHA] Class III or IV) or uncontrolled cardiac arrhythmia
- •Female subjects who are pregnant or lactating
- •Congenital or acquired immune deficiency
- •Current or history of documented or suspected malignancy of any organ system (diagnosed, treated or untreated) within the past 5 years (with the exception of localized transitional cell carcinoma of the ureter treated with ureterectomy or nephroureterectomy, adequately treated basal cell or squamous cell carcinoma of the skin or asymptomatic non-metastatic prostrate cancer either previously successfully treated or currently under active surveillance or receiving hormone therapy only)
- •Bladder contracture or history of an inability to retain the instillate for a minimum of 1 hour, even with premedication
- •Any medical or psychiatric condition which, in the opinion of the investigator, would preclude the participant from adhering to the protocol or completing the trial per protocol.
结局指标
主要结局
The primary objective of this study is to evaluate the efficacy of EN3348 as compared with mitomycin C in the treatment of subjects with BCG recurrent or refractory NMIBC
时间窗: The primary outcome is measured as "event free survival" | Event free survival is measured from the time of randomization till an occurance of an event in a subject. | Event is defined as tumor recurrence, tumor progression to muscle invasive bladder cancer | (MIBC) or death, whichever occurs first.
次要结局
- The secondary objective is to evaluate the safety of EN3348 as compared with mitomycin C in the treatment of subjects with BCG recurrent or refractory NMIBC.(• Event-free survival rate at 1 and 2 years)