Pharmacodynamic Trial of Pre-Prostatectomy Lovastatin on MYC (V-myc Myelocytomatosis Viral Oncogene Homolog) Down-Regulation in Localized Prostate Cancer
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.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Number of participants that can achieve 60% MYC modulation response
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.
Phouc Tran, M.D.
Johns Hopkins University
United States: Institutional Review Board
|The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins||Baltimore, Maryland 21231|