Pre-Prostatectomy Lovastatin on Prostate Cancer
|ClinicalTrials.gov Identifier: NCT01478828|
Recruitment Status : Suspended (The study was stopped due to an unanticipated serious adverse event.)
First Posted : November 23, 2011
Results First Posted : November 9, 2015
Last Update Posted : November 9, 2015
|Condition or disease||Intervention/treatment||Phase|
|Prostate Cancer||Drug: Lovastatin||Not Applicable|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||2 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Pharmacodynamic Trial of Pre-Prostatectomy Lovastatin on MYC (V-myc Myelocytomatosis Viral Oncogene Homolog) Down-Regulation in Localized Prostate Cancer|
|Study Start Date :||March 2012|
|Actual Primary Completion Date :||April 2013|
|Estimated Study Completion Date :||April 2016|
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.
oral qd varying dose escalations/de-escalations
Other Name: Altoprev®; Mevacor®
- Number of Participants That Can Achieve 60% MYC Modulation Response [ Time Frame: 1 year ]To determine the dose of continuous daily oral lovastatin needed to achieve MYC down-regulation in prostatectomy specimens in intermediate-/high-risk localized prostate cancer patients.
- Number of Participants Who Experience Specific Adverse Events at Different Dosing Points Prior to Surgery. [ Time Frame: 1 year ]1. To assess the tolerability and toxicity of the different doses of continuous daily oral lovastatin in generally healthy men with prostate cancer prior to surgery.
- To Estimate What the Doses Given to Men With MYC Target Inhibition When Factoring in Their Tumor Biopsies Before and After Lovastatin Treatment. [ Time Frame: 1 year ]2. To estimate an overall and per dose proportion of men with MYC target inhibition in prostate tumor tissue using paired tumor biopsies before and after lovastatin administration.
- Number and Type of Cholesterol Changes After Lovastatin Treatments. [ Time Frame: 1 year ]3. To characterize the effect of continuous daily oral lovastatin on cholesterol level in this patient population, at the doses tested in this trial.
- Capture the Pharmacodynamic Changes in Participants After the Pre-treatment Biopsy. [ Time Frame: 1 year ]4. To assess the relationship of pharmacodynamic target inhibition of MYC with pretreatment prostate biopsy Gleason sum, Ki-67, and degree of MYC overexpression.
- Capture the Associated Changes in Participants With Regards to the Relationship Between MYC and Increased Apoptosis. [ Time Frame: 1 year ]5. To assess an association of pharmacodynamic target inhibition of MYC with markers of increased apoptosis (cleaved caspase-3) and proliferation (Ki-67).
- Number of Participants Who Follow All of the Study Rules. [ Time Frame: 1 year ]6. To assess the study compliance.
- Capture Difference in MYC Downregulation Between Treated Participants and Non-treated Patients [ Time Frame: 1 year ]7. To compare the MYC downregulation between our prostatectomy samples treated with high-dose lovastatin and up to 21 matched prostatectomy reference samples from untreated patients from a pre-existing reference dataset.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01478828
|United States, Maryland|
|The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins|
|Baltimore, Maryland, United States, 21231|
|Principal Investigator:||Phouc Tran, M.D.||Johns Hopkins University|