Novel Window of Opportunity Trial to Evaluate the Impact of Statins to Oppose Prostate Cancer

Study Overview
=================
Brief Summary
-----------------
This research study provides a novel opportunity to examine the intra-prostatic tumour inhibitory effects of statins in men with prostate cancer undergoing surgery.

Official Title
-----------------
Novel Window of Opportunity Trial to Evaluate the Impact of Statins to Oppose Prostate Cancer

Conditions
-----------------
Prostate Cancer

Intervention / Treatment
-----------------
* Drug: Fluvastatin
* Drug: Pimonidazole


Participation Criteria
=================
Eligibility Criteria
-----------------
The study population will consist of patients with localized prostate cancer that have elected radical prostatectomy as a primary treatment. Eligible patients will have prostate cancer that is Gleason Score ≥ 7. Patients who meet all of the following inclusion criteria will be eligible to participate in this study: Men >18 and < 75 years of age Willing and able to provide informed consent, either alone or with the aid of a translator Histologically confirmed prostate cancer as determined by transrectal ultrasound (TRUS) guided prostate biopsy performed within 6 months of study enrolment Prostate cancer that is Gleason grade ≥ 7 involving at least 30% of one unfragmented biopsy core Candidates for radical prostatectomy considered surgically resectable, either open or robotic, by urologic evaluation Normal organ and marrow function as defined by the following criteria: i. absolute neutrophil count >1,500/uL ii. platelets >100,000/uL iii. total bilirubin <1.5 X institutional ULN iv. AST (SGOT) or ALT (SGPT) <1.5 X institutional ULN v. creatinine <1.5 X institutional ULN Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 Exclusion Criteria Any patient meeting one or more of the following exclusion criteria may not be entered into the study: Previous or current use of neo-adjuvant or hormonal management of prostate cancer (surgical castration or other hormonal manipulation, including GnRH receptor agonists, GnRH receptor antagonists, anti-androgens, estrogens, megestrol acetate and ketoconazole) History of receiving radiation to the pelvic area Past or current use of 5-alpha reductase inhibitors finasteride and/or dutasteride History of bilateral orchiectomy, adrenalectomy, or hypophysectomy Statin use within 2 years of prostate cancer diagnosis Known hypersensitivity towards any component of the investigational medicinal product. Previous history or presence of another malignancy, other than prostate cancer or treated squamous / basal cell carcinoma of the skin, within the last five years Clinically significant laboratory abnormalities (e.g. severe renal or hepatic impairment) which in the judgment of the Investigator would affect the patient's health or the outcome of the trial Clinically significant disorder (other than prostate cancer) including, but not limited to, renal, haematological, gastrointestinal, endocrine, cardiac, neurological, or psychiatric disease, and alcohol or drug abuse or any other condition, which may affect the patient's health or the outcome of the trial as judged by the Investigator Use of natural medicines thought to have endocrine effects on prostate cancer (e.g. saw palmetto and St. John's Wort) 4 weeks prior to enrollment. Use of any drug listed in Prohibited Medications List Mental incapacity or language barrier precluding adequate understanding or co operation Use of an investigational drug within the last 28 days preceding the Screening Visit or longer if considered to possibly influence the outcome of the current trial Patients who are unable or unwilling to undergo MRI testing

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fluvastatin/Pimonidazole<br>Patients will take 40mg BID of fluvastatin. The day before surgery patients will take a single dose of pimonidazole that will be calculate based on body surface area. | Drug: Fluvastatin<br>* HMG-CoA reductase inhibitors that lowers cholesterol levels. 40mg twice daily<br>* Other names: Lescol;Drug: Pimonidazole<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pre and post treatment effect on the Ki-67 proliferation index |  | Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of immunohistochemical staining in Biopsy and post-RP tissues | Will measure: i. Apoptosis (caspase 3) ii. Signaling (Rap1A, Rap, RhoB) iii. Mevalonate pathway proteins (HMG-CoA reductase, HMG-CoA synthase, SREBP1/2, mevalonate decarboxylase, GGPS1, GGT, FT) iv. Tumour Infiltrating Lymphocytes (TILs), CD3 (T-cells), CD20 (B-cells), CD68 (macrophages), CD56 (NK cells), IDO (negative control)) v. Growth and survival signaling (AKT, P-AKT, ERK, P-ERK) | Week 8 |