Metformin and Simvastatin Use in Bladder Cancer
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|ClinicalTrials.gov Identifier: NCT02360618|
Recruitment Status : Recruiting
First Posted : February 10, 2015
Last Update Posted : July 11, 2016
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.
|Condition or disease||Intervention/treatment||Phase|
|Bladder Cancer||Drug: Metformin Drug: Simvastatin||Phase 2|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||44 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Window of Opportunity Study to Evaluate the Role of the Combination of Metformin and Simvastatin as a Neoadjuvant Therapy in Invasive Bladder Cancer|
|Study Start Date :||October 2015|
|Estimated Primary Completion Date :||January 2018|
|Estimated Study Completion Date :||January 2018|
Experimental: 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.
See Group Description
Other Name: No other namesDrug: Simvastatin
See Group Description
Other Name: No other names
- Bladder tumor proliferation rate [ Time Frame: 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 [ Time Frame: 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.
- Toxicity in patients who participate in the treatment regimen of Metformin and Simvastatin therapy [ Time Frame: The participant will be followed for the duration of the pre-surgical preparation period. This is expected to be fewer than 12 weeks ]This study will assess the rate of grade 3 or higher toxicity caused by the study drug combination as defined by the CTCAE 4.03.
- Level of apoptosis observed in tumor cells of patients who undergo Metformin and Simvastatin therapy before cystectomy. [ Time Frame: The participant will be followed for the duration of the pre-surgical preparation period. This is expected to be fewer than 12 weeks ]Tissue will be analyzed for the change in the marker of apoptosis Terminal deoxynucleotidyl Transferase-mediated dUTP nick end labeling (TUNEL) staining between TURBT and cystectomy tissue samples.
- Impact of Metformin and Simvastatin therapy on the signalling pathways involved in invasive urothelial carcinoma. [ Time Frame: The participant will be followed for the duration of the pre-surgical preparation period. This is expected to be fewer than 12 weeks ]Various signalling pathways involved in cell proliferation and metformin response that may be affected by the combination of study drugs will be evaluated by analyzing tissue samples obtained from the patient during TURBT and then cystectomy. These experiments will be done to assess whether the combination of study drugs are able to inhibit the cellular signalling pathways that contribute to cancer cell growth by comparing the signaling levels between pre and post treatment samples. These pathways include PI3K/Akt/mTOR and AMPK. We will also evaluate the effect of the levels of PTEN and p53 on the cell response to therapy.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02360618
|Contact: Jonathan Izawa, MD||519-685-8500 ext firstname.lastname@example.org|
|Contact: Catherine Hildebrand, PhD||519-685-8500 ext 53535||Catherine.Hildebrand@lhsc.on.ca|
|London Health Sciences Center; Victoria Hospital||Recruiting|
|London, Ontario, Canada, N6A 5W9|
|Contact: Jonathan Izawa, MD|
|Principal Investigator:||Jonathan Izawa, MD||London Health Sciences Centre|