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Pharmacodynamic Trial of Pre-Prostatectomy Lovastatin on MYC (V-myc Myelocytomatosis Viral Oncogene Homolog) Down-Regulation in Localized Prostate Cancer

18 Years
Not Enrolling
Prostate Cancer

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Trial Information

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.

Inclusion Criteria:

1. Adenocarcinoma of the prostate, without evidence of spread beyond to lymph nodes,
bone, or visceral organs, stage T1c or higher.

2. 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).

3. Age ≥18 years of age.

4. Radical prostatectomy scheduled at Johns Hopkins.

5. Willingness to sign and ability to understand informed consent.

6. No history of treatment with any statin-class medication within 6 months of entry
into the trial.

7. ECOG (Eastern Cooperative Oncology Group) performance status 0-1.

8. 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:

1. Patients with evidence of metastatic prostate cancer, including bone, visceral,
brain, and lymph node metastases.

2. Other histologic prostate cancers, including ductal, sarcomatous, lymphoma, small
cell, and neuroendocrine tumors.

3. 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.

4. Concurrent malignancy other than prostate cancer.

5. Inability to provide informed consent.

6. Concomitant use of azole antifungals, cyclosporine, clarithromycin, erythromycin,
fibric acid derivatives, lopinavir/ritonavir, niacin, ritonavir/saquinavir

7. Prior chemotherapy, radiation therapy, biologic therapy, or immunotherapy for
prostate cancer.

8. Poor performance status (ECOG >1).

9. Prostatectomy at other hospital other than Johns Hopkins.

10. Prior history of allergy or severe reaction to statins or statin derivatives.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Number of participants that can achieve 60% MYC modulation response

Outcome Description:

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.

Outcome Time Frame:

1 year

Safety Issue:


Principal Investigator

Phouc Tran, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Johns Hopkins University


United States: Institutional Review Board

Study ID:




Start Date:

March 2012

Completion Date:

April 2013

Related Keywords:

  • Prostate Cancer
  • Prostatic Neoplasms



The Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsBaltimore, Maryland  21231