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

Primary Purpose

Prostate Cancer

Status
Completed
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
Fluvastatin
Pimonidazole
Sponsored by
University Health Network, Toronto
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Prostate Cancer

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)MaleDoes not accept healthy volunteers

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:

  1. Men >18 and < 75 years of age
  2. Willing and able to provide informed consent, either alone or with the aid of a translator
  3. Histologically confirmed prostate cancer as determined by transrectal ultrasound (TRUS) guided prostate biopsy performed within 6 months of study enrolment
  4. Prostate cancer that is Gleason grade ≥ 7 involving at least 30% of one unfragmented biopsy core
  5. Candidates for radical prostatectomy considered surgically resectable, either open or robotic, by urologic evaluation
  6. 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

  7. 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:

  1. 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)
  2. History of receiving radiation to the pelvic area
  3. Past or current use of 5-alpha reductase inhibitors finasteride and/or dutasteride
  4. History of bilateral orchiectomy, adrenalectomy, or hypophysectomy
  5. Statin use within 2 years of prostate cancer diagnosis
  6. Known hypersensitivity towards any component of the investigational medicinal product.
  7. 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
  8. 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
  9. 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
  10. 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.
  11. Use of any drug listed in Prohibited Medications List
  12. Mental incapacity or language barrier precluding adequate understanding or co operation
  13. 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
  14. Patients who are unable or unwilling to undergo MRI testing

Sites / Locations

  • University Health Network- The Princess Margaret Cancer Centre

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Fluvastatin/Pimonidazole

Arm Description

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.

Outcomes

Primary Outcome Measures

Pre and post treatment effect on the Ki-67 proliferation index

Secondary Outcome Measures

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)

Full Information

First Posted
November 18, 2013
Last Updated
October 24, 2017
Sponsor
University Health Network, Toronto
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1. Study Identification

Unique Protocol Identification Number
NCT01992042
Brief Title
Novel Window of Opportunity Trial to Evaluate the Impact of Statins to Oppose Prostate Cancer
Official Title
Novel Window of Opportunity Trial to Evaluate the Impact of Statins to Oppose Prostate Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
October 2017
Overall Recruitment Status
Completed
Study Start Date
February 2014 (Actual)
Primary Completion Date
October 2016 (Actual)
Study Completion Date
December 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Health Network, Toronto

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
33 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Fluvastatin/Pimonidazole
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Fluvastatin
Other Intervention Name(s)
Lescol
Intervention Description
HMG-CoA reductase inhibitors that lowers cholesterol levels. 40mg twice daily
Intervention Type
Drug
Intervention Name(s)
Pimonidazole
Primary Outcome Measure Information:
Title
Pre and post treatment effect on the Ki-67 proliferation index
Time Frame
Week 8
Secondary Outcome Measure Information:
Title
Comparison of immunohistochemical staining in Biopsy and post-RP tissues
Description
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)
Time Frame
Week 8

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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
Facility Information:
Facility Name
University Health Network- The Princess Margaret Cancer Centre
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G2M9
Country
Canada

12. IPD Sharing Statement

Citations:
PubMed Identifier
32203069
Citation
Longo J, Hamilton RJ, Masoomian M, Khurram N, Branchard E, Mullen PJ, Elbaz M, Hersey K, Chadwick D, Ghai S, Andrews DW, Chen EX, van der Kwast TH, Fleshner NE, Penn LZ. A pilot window-of-opportunity study of preoperative fluvastatin in localized prostate cancer. Prostate Cancer Prostatic Dis. 2020 Dec;23(4):630-637. doi: 10.1038/s41391-020-0221-7. Epub 2020 Mar 13.
Results Reference
derived

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

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