Metformin and Simvastatin Use in Bladder Cancer

• Status: Unknown status
• Trial end date: 2018-01-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: London Health Sciences Centre
• Treatments: Metformin; Simvastatin

Criteria

Inclusion Criteria

1. Age ≥18 years and 85≤.

2. Patients must have biopsy proven invasive bladder cancer by TURBT, previously untreated prior to TURBT by systemic chemotherapy.

3. Patients must be able to swallow and tolerate oral medication

4. Hemoglobin A1c ≤ 6.5%.

5. Able to comprehend written and verbal study instructions related to study protocol and provide informed consent.

6. Any women with childbearing potential must use a highly effective contraception method, of which include: hormonal contraceptives (e.g. combined oral contraceptives, patch, vaginal ring, injectables, and implants); intrauterine device (IUD) or intrauterine system (IUS); vasectomy and tubal ligation.

Exclusion Criteria

1. Patient has been treated for a prior cancer diagnosis with cisplatin-derived chemotherapy regimens or has had pelvic radiation therapy.

2. Previous or current diagnosis of type 1 or 2 diabetes mellitus.

3. Metformin exposure within the previous 12 months.

4. Expected or simultaneous use of sulfonylureas, thiazolidinediones, or insulin.

5. Known metformin allergy or intolerance.

6. Participation in another drug trial either within 30 days prior to study enrollment or during the time when they are on study protocol.

7. Serious cardiovascular disease including myocardial infarction within 6 months, unstable angina, serious cardiac arrythmias excluding atrial fribrillation, or cerebrovascular accident within 6 months prior to screening visit.

8. Abnormal liver function tests: Total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), or alkaline phosphatase (ALP) > 1.8 X upper limit of normal

9. Estimated glomerular filtration rate (eGFR) of ≤40 mL/min.

10. History of other malignancy, except non-muscle invasive bladder cancer, treated non-melanoma skin cancer, stage I melanoma and solid tumors adequately treated, with no persistent evidence of disease for 5 years.

11. Concomitant medical condition predisposing to metformin hydrochloride-associated lactic acidosis; examples include NYHA class III or IV congestive heart failure, history of acidosis and chronic alcohol intake averaging ≥ 4 beverages per day.

12. A history of rhabdomyolysis.

13. The use of medications including niacin and colchicine, as well as strong inhibitors of cytochrome p-450 3A4 (see list in section 4.2).

14. Untreated hypothyroidism.

15. Pregnancy.

16. Breastfeeding