Metformin and Simvastatin Use in Bladder Cancer

NCT02360618 | Unknown Phase 2 DMC

• 1 other identifier: MS_1
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Bladder Cancer

Keywords

Bladder Cancer; Metformin; Simvastatin; Combination Therapy

Outcome Measures

Primary Outcomes (2)

• Bladder tumor proliferation rate

  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.

  The participant will be followed for the duration of the pre-surgical preparation period. This is expected to be fewer than 12 weeks

• Feasibility of performing neoadjuvant window of opportunity trials using drugs with potential bioactivity against invasive bladder cancer

  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.

  The participant will be followed for the duration of the pre-surgical preparation period. This is expected to be fewer than 12 weeks

Secondary Outcomes (3)

• 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

• 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

Study Arms (1)

Metformin and Simvastatin Treatment

EXPERIMENTAL

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.

Drug: Metformin; Drug: Simvastatin

Interventions

Metformin DRUG

See Group Description

Also known as: No other names

Metformin and Simvastatin Treatment

Simvastatin DRUG

See Group Description

Also known as: No other names

Metformin and Simvastatin Treatment

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years and 85≤.
• Patients must have biopsy proven invasive bladder cancer by TURBT, previously untreated prior to TURBT by systemic chemotherapy.
• Patients must be able to swallow and tolerate oral medication
• Hemoglobin A1c ≤ 6.5%.
• Able to comprehend written and verbal study instructions related to study protocol and provide informed consent.
• 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.

You may not qualify if:

• Patient has been treated for a prior cancer diagnosis with cisplatin-derived chemotherapy regimens or has had pelvic radiation therapy.
• Previous or current diagnosis of type 1 or 2 diabetes mellitus.
• Metformin exposure within the previous 12 months.
• Expected or simultaneous use of sulfonylureas, thiazolidinediones, or insulin.
• Known metformin allergy or intolerance.
• Participation in another drug trial either within 30 days prior to study enrollment or during the time when they are on study protocol.
• 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.
• Abnormal liver function tests: Total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), or alkaline phosphatase (ALP) \> 1.8 X upper limit of normal
• Estimated glomerular filtration rate (eGFR) of ≤40 mL/min.
• 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.
• 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.
• A history of rhabdomyolysis.
• The use of medications including niacin and colchicine, as well as strong inhibitors of cytochrome p-450 3A4 (see list in section 4.2).
• Untreated hypothyroidism.
• Pregnancy.

Sponsors & Collaborators

• London Health Sciences Centre: lead

Study Sites (1)

London Health Sciences Center; Victoria Hospital

London, Ontario, N6A 5W9, Canada

RECRUITING

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

Metformin; Simvastatin

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds

Study Officials

• Jonathan Izawa, MD

  London Health Sciences Centre

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jonathan Izawa, MD

CONTACT

519-685-8500; jonathan.izawa@lhsc.on.ca

Catherine Hildebrand, PhD

CONTACT

519-685-8500; Catherine.Hildebrand@lhsc.on.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Urologic Surgeon

Study Record Dates

• First Submitted: January 13, 2015
• First Posted: February 10, 2015
• Study Start: October 1, 2015
• Primary Completion: January 1, 2018
• Study Completion: January 1, 2018
• Last Updated: July 11, 2016

Record last verified: 2016-07

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)