A Window of Opportunity Study to Evaluate the Role of the Combination of Metformin and Simvastatin as a Neoadjuvant Therapy in Invasive Bladder Cancer
试验速览
- 阶段
- 2 期
- 入组人数
- 44
- 试验地点
- 1
- 主要终点
- Bladder tumor proliferation rate
研究概览
简要总结
A single arm, single center window of opportunity trial of using a combination of metformin and simvastatin as a neoadjuvant treatment for patients with invasive bladder cancer who are to undergo cystectomy. The study will assess the feasibility of conducting window of opportunity trials in invasive bladder cancer the drug combination's affects on a variety of important clinicopathologic variables.
The goal is to enroll 44 patients within 18 months. An interim analysis will be conducted at 12 months, and the study will be prematurely closed if fewer than 10 patients have been enrolled at that time. Patients will be administered 850mg of metformin twice daily along with 20mg of Simvastatin. Patients will be enrolled following the formal diagnosis of invasive bladder cancer or at first visit following referral to the London Health Sciences Center (LHSC). Patient's will receive metformin and simvastatin from the time of enrollment until the night prior to their operation in the absence of safety or tolerability concerns.
详细描述
This is a single centre window of opportunity trial. A total of 44 patients with a diagnosis of invasive bladder cancer diagnosed by pathologic evaluation of transurethral resection of bladder tumor (TURBT) specimens and meeting all eligibility criteria will be enrolled in the study. Study participants will receive Metformin 850mg twice daily and simvastatin 20mg once daily until the night before of their scheduled cystectomy, which is a time period which will last approximately 12 weeks or less. Pre-treatment TURBT tissue samples and the Cystectomy post-therapy tissue samples will be analyzed and compared. Samples will be analyzed for cell proliferation markers and to determine whether or not the combination of metformin and simvastatin is able to produce a synergistic effect that will result in the decrease of the growth of these aggressive cancer cells. The anticipated recruitment period will be approximately 18 months. Participants in this study will be asked to attend the following clinic visits for this study:
Baseline Visit:
During this visit, the study doctor will conduct a physical exam and take vital signs as well as height and weight measurements. Blood will also be drawn for analysis and research purposes. Females that are of child bearing potential will have a pregnancy test to confirm that they are not pregnant. Pregnant women will be removed from the study. We will also be collecting blood samples.
Clinic Visits Participants will have follow-up clinic visits or phone interviews scheduled every 4 weeks until the time of their surgery. At least 1 visit will be in person before surgery. At these times they will have blood drawn for analysis, have their medication reviewed, and confirm that they are taking the medication in adherence with the study protocol.
Day of Surgery On the day of surgery, the participants will have their height and weight measured, have blood drawn for analysis and research purposes, and drug compliance will be assessed.
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 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Metformin and Simvastatin Treatment
Patients in this group will receive 850 mg of Metformin and 20 mg of Simvastatin daily from the time they are enrolled in the study until the day before their surgery (approximately 12 weeks), in the absence of any safety or tolerability concerns.
干预措施: Metformin (Drug)
Metformin and Simvastatin Treatment
Patients in this group will receive 850 mg of Metformin and 20 mg of Simvastatin daily from the time they are enrolled in the study until the day before their surgery (approximately 12 weeks), in the absence of any safety or tolerability concerns.
干预措施: Simvastatin (Drug)
结局指标
主要结局
Bladder tumor proliferation rate
时间窗: The participant will be followed for the duration of the pre-surgical preparation period. This is expected to be fewer than 12 weeks
The primary endpoint of this trial will be the assessment of the tumor proliferation rate. This will be investigated through the analysis of the change in Ki67 (cellular marker of cell proliferation) tissue staining between the TURBT tissue samples and the cystectomy tissue.
Feasibility of performing neoadjuvant window of opportunity trials using drugs with potential bioactivity against invasive bladder cancer
时间窗: The participant will be followed for the duration of the pre-surgical preparation period. This is expected to be fewer than 12 weeks
This trial is also designed to establish the framework and evaluate the feasibility of performing neoadjuvant window of opportunity trials using drugs with potential bioactivity against invasive bladder cancer at the London Health Sciences Center. The goal is to accrue 44 patients within 18 months to the trial, and the study will be prematurely closed if fewer than 10 patients are recruited within 12 months.
次要结局
- Impact of Metformin and Simvastatin therapy on the signalling pathways involved in invasive urothelial carcinoma.(The participant will be followed for the duration of the pre-surgical preparation period. This is expected to be fewer than 12 weeks)
- Toxicity in patients who participate in the treatment regimen of Metformin and Simvastatin therapy(The participant will be followed for the duration of the pre-surgical preparation period. This is expected to be fewer than 12 weeks)
- Level of apoptosis observed in tumor cells of patients who undergo Metformin and Simvastatin therapy before cystectomy.(The participant will be followed for the duration of the pre-surgical preparation period. This is expected to be fewer than 12 weeks)
研究者
Dr. Jonathan Izawa
Urologic Surgeon
London Health Sciences Centre