Back to resultsPre-Prostatectomy Lovastatin on Prostate Cancer
Primary Purpose
Prostate Cancer
Status
Terminated
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Lovastatin
Sponsored by
About this trial
This is an interventional treatment trial for Prostate Cancer
Eligibility Criteria
Inclusion Criteria:
- Adenocarcinoma of the prostate, without evidence of spread beyond to lymph nodes, bone, or visceral organs, stage T1c or higher.
- Tumor Gleason sum of 7 (4+3 and 3+4 allowed) in at least one core, after central review of prostate biopsy at Johns Hopkins. However, in accordance with standard clinical practices, adenocarcinoma must be present in at least two discrete biopsy sections ( may vary in Gleason score).
- Age ≥18 years of age.
- Radical prostatectomy scheduled at Johns Hopkins.
- Willingness to sign and ability to understand informed consent.
- No history of treatment with any statin-class medication within 6 months of entry into the trial.
- ECOG (Eastern Cooperative Oncology Group) performance status 0-1.
- Adequate bone marrow, hepatic, and renal function as determined by:
WBC (white blood cells) >3,500 cells/mm3 ANC (absolute neutrophil count) >1,500 cells/mm3 Hemoglobin >9 g/dl Platelet count >100,000 cells/mm3 Serum creatinine < 2.6 mg/dl Serum bilirubin <2 mg/dl ALT (alanine aminotransferase), AST (aspartate aminotransferase), and Alkaline Phosphatase <2 times the upper limit of normal Triglycerides and total cholesterol <3 times the upper limit of normal
Exclusion Criteria:
- Patients with evidence of metastatic prostate cancer, including bone, visceral, brain, and lymph node metastases.
- Other histologic prostate cancers, including ductal, sarcomatous, lymphoma, small cell, and neuroendocrine tumors.
- Uncontrolled medical conditions that could potentially increase the risk of toxicities or complications of this therapy including active liver disease, unexplained persistent elevation of serum transaminases, or medications that interfere with the metabolism of lovastatin, or gastrointestinal disease that would limit the ability to swallow or take oral medications or absorb them.
- Concurrent malignancy other than prostate cancer.
- Inability to provide informed consent.
- Concomitant use of azole antifungals, cyclosporine, clarithromycin, erythromycin, fibric acid derivatives, lopinavir/ritonavir, niacin, ritonavir/saquinavir
- Prior chemotherapy, radiation therapy, biologic therapy, or immunotherapy for prostate cancer.
- Poor performance status (ECOG >1).
- Prostatectomy at other hospital other than Johns Hopkins.
- Prior history of allergy or severe reaction to statins or statin derivatives.
Sites / Locations
- The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Lovastatin
Arm Description
After informed consent and central pathology review of the core prostate biopsy, eligible patients who decide to undergo prostatectomy at Johns Hopkins will be scheduled to receive po lovastatin following a four times a day schedule, at the starting dose of 20 mg/kg/day. Following an initial period of monitoring for safety at this entry dose level of one month, we will then accrue patients to dose de-escalation (to 1, and 10 mg/kg/day) cohorts.
Outcomes
Primary Outcome Measures
Number of Participants That Can Achieve 60% MYC Modulation Response
Number of participants who achieve V-myc Myelocytomatosis Viral Oncogene Homolog (MYC) down-regulation in prostatectomy specimens in intermediate-/high-risk localized prostate cancer patients.
Secondary Outcome Measures
Number of Participants Who Experience Specific Adverse Events at Different Dosing Points Prior to Surgery.
Toxicity of the different doses of continuous daily oral lovastatin in generally healthy men with prostate cancer prior to surgery.
Proportion of Men With MYC Target Inhibition in Prostate Tumor Tissue
Proportion of men with MYC target inhibition in prostate tumor tissue using paired tumor biopsies before and after lovastatin administration.
Change in Cholesterol Level After Lovastatin Treatments.
Change in cholesterol level with each tested dose of oral lovastatin.
Pharmacodynamic Changes in Participants After the Pre-treatment Biopsy as Measured by Number of Participants With Target Inhibition of MYC
Number of participants with target inhibition of MYC in relationship with pretreatment prostate biopsy Gleason sum, Ki-67, and degree of MYC overexpression.
Number of Participants With Target Inhibition of MYC and Increased Apoptosis and Proliferation
Number of participants with target inhibition of MYC and markers of increased apoptosis (cleaved caspase-3) and proliferation (Ki-67).
Study Compliance as Assessed by Number of Participants Who Follow All of the Study Rules.
Number of Participants With MYC Downregulation
Number of participants with MYC downregulation after high-dose lovastatin.
Full Information
NCT ID
NCT01478828
First Posted
November 3, 2011
Last Updated
March 14, 2019
Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators
Patrick C Walsh Prostate Cancer Research Fund
1. Study Identification
Unique Protocol Identification Number
NCT01478828
Brief Title
Pre-Prostatectomy Lovastatin on Prostate Cancer
Official Title
Pharmacodynamic Trial of Pre-Prostatectomy Lovastatin on MYC (V-myc Myelocytomatosis Viral Oncogene Homolog) Down-Regulation in Localized Prostate Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
March 2019
Overall Recruitment Status
Terminated
Why Stopped
The study was stopped due to an unanticipated serious adverse event.
Study Start Date
July 13, 2012 (Actual)
Primary Completion Date
April 8, 2013 (Actual)
Study Completion Date
April 8, 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators
Patrick C Walsh Prostate Cancer Research Fund
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
To determine the dose of continuous daily oral lovastatin needed to achieve MYC [v-myc myelocytomatosis viral oncogene homolog (avian)] down-regulation in prostatectomy specimens in intermediate-/high-risk localized prostate cancer patients.
Detailed Description
Pharmacodynamic Phase 0 trial of pre-prostatectomy lovastatin to downregulate MYC in localized prostate cancer.
Rationale: Based on available clinical and preclinical data, the investigators theorize that high-dose lovastatin therapy will decrease MYC levels in human prostate cancers shown to have MYC overexpression on biopsy.
Experimental Methods: The investigators propose a prospective, dose-finding pharmacodynamic study of lovastatin in intermediate/high-grade localized prostate cancer. The study will involve 30 eligible patients with localized prostate cancer with a Gleason sum of 7 to 10 who elect to undergo prostatectomy at Johns Hopkins. Five eligible men will be scheduled to receive oral lovastatin following a four times a day schedule, at the starting dose of 12 mg/kg/day. Patients will receive 2 weeks (14 days) of daily oral lovastatin prior to surgery. Following an initial safety monitoring period of a month, the investigators enroll at the next dose level (20 mg/kg/day). Similar dose de-escalation will continue over three more dose levels (1, 4 and 8 mg/kg/day) until 25 patients total are enrolled. Following surgery, prostatectomy specimens will undergo MYC immunohistochemistry (IHC) and compared to MYC IHC from matched biopsy samples. Pharmacodynamic efficacy (PE) will be defined as greater than 60% inhibition of MYC expression by IHC in greater than 60% of patients in prostatectomy tumor specimens compared to the matched biopsy.
Expected Results: The investigators expect lovastatin will enforce the downregulation of MYC levels in prostatectomy samples as compared to pre-lovastatin treatment core biopsy samples. The investigators also expect little toxicity to patients as reported in prior phase I and II trials using similar doses of lovastatin.
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
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
2 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Lovastatin
Arm Type
Experimental
Arm Description
After informed consent and central pathology review of the core prostate biopsy, eligible patients who decide to undergo prostatectomy at Johns Hopkins will be scheduled to receive po lovastatin following a four times a day schedule, at the starting dose of 20 mg/kg/day. Following an initial period of monitoring for safety at this entry dose level of one month, we will then accrue patients to dose de-escalation (to 1, and 10 mg/kg/day) cohorts.
Intervention Type
Drug
Intervention Name(s)
Lovastatin
Other Intervention Name(s)
Altoprev®; Mevacor®
Intervention Description
oral qd varying dose escalations/de-escalations
Primary Outcome Measure Information:
Title
Number of Participants That Can Achieve 60% MYC Modulation Response
Description
Number of participants who achieve V-myc Myelocytomatosis Viral Oncogene Homolog (MYC) down-regulation in prostatectomy specimens in intermediate-/high-risk localized prostate cancer patients.
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Number of Participants Who Experience Specific Adverse Events at Different Dosing Points Prior to Surgery.
Description
Toxicity of the different doses of continuous daily oral lovastatin in generally healthy men with prostate cancer prior to surgery.
Time Frame
1 year
Title
Proportion of Men With MYC Target Inhibition in Prostate Tumor Tissue
Description
Proportion of men with MYC target inhibition in prostate tumor tissue using paired tumor biopsies before and after lovastatin administration.
Time Frame
1 year
Title
Change in Cholesterol Level After Lovastatin Treatments.
Description
Change in cholesterol level with each tested dose of oral lovastatin.
Time Frame
1 year
Title
Pharmacodynamic Changes in Participants After the Pre-treatment Biopsy as Measured by Number of Participants With Target Inhibition of MYC
Description
Number of participants with target inhibition of MYC in relationship with pretreatment prostate biopsy Gleason sum, Ki-67, and degree of MYC overexpression.
Time Frame
1 year
Title
Number of Participants With Target Inhibition of MYC and Increased Apoptosis and Proliferation
Description
Number of participants with target inhibition of MYC and markers of increased apoptosis (cleaved caspase-3) and proliferation (Ki-67).
Time Frame
1 year
Title
Study Compliance as Assessed by Number of Participants Who Follow All of the Study Rules.
Time Frame
1 year
Title
Number of Participants With MYC Downregulation
Description
Number of participants with MYC downregulation after high-dose lovastatin.
Time Frame
1 year
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Adenocarcinoma of the prostate, without evidence of spread beyond to lymph nodes, bone, or visceral organs, stage T1c or higher.
Tumor Gleason sum of 7 (4+3 and 3+4 allowed) in at least one core, after central review of prostate biopsy at Johns Hopkins. However, in accordance with standard clinical practices, adenocarcinoma must be present in at least two discrete biopsy sections ( may vary in Gleason score).
Age ≥18 years of age.
Radical prostatectomy scheduled at Johns Hopkins.
Willingness to sign and ability to understand informed consent.
No history of treatment with any statin-class medication within 6 months of entry into the trial.
ECOG (Eastern Cooperative Oncology Group) performance status 0-1.
Adequate bone marrow, hepatic, and renal function as determined by:
WBC (white blood cells) >3,500 cells/mm3 ANC (absolute neutrophil count) >1,500 cells/mm3 Hemoglobin >9 g/dl Platelet count >100,000 cells/mm3 Serum creatinine < 2.6 mg/dl Serum bilirubin <2 mg/dl ALT (alanine aminotransferase), AST (aspartate aminotransferase), and Alkaline Phosphatase <2 times the upper limit of normal Triglycerides and total cholesterol <3 times the upper limit of normal
Exclusion Criteria:
Patients with evidence of metastatic prostate cancer, including bone, visceral, brain, and lymph node metastases.
Other histologic prostate cancers, including ductal, sarcomatous, lymphoma, small cell, and neuroendocrine tumors.
Uncontrolled medical conditions that could potentially increase the risk of toxicities or complications of this therapy including active liver disease, unexplained persistent elevation of serum transaminases, or medications that interfere with the metabolism of lovastatin, or gastrointestinal disease that would limit the ability to swallow or take oral medications or absorb them.
Concurrent malignancy other than prostate cancer.
Inability to provide informed consent.
Concomitant use of azole antifungals, cyclosporine, clarithromycin, erythromycin, fibric acid derivatives, lopinavir/ritonavir, niacin, ritonavir/saquinavir
Prior chemotherapy, radiation therapy, biologic therapy, or immunotherapy for prostate cancer.
Poor performance status (ECOG >1).
Prostatectomy at other hospital other than Johns Hopkins.
Prior history of allergy or severe reaction to statins or statin derivatives.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Phouc Tran, M.D.
Organizational Affiliation
Johns Hopkins University
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21231
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Pre-Prostatectomy Lovastatin on Prostate Cancer
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