An interventional study of Lovastatin in Prostate Cancer, sponsored by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins. Terminated at 1 site in United States. Open to male participants aged 18 Years to 100 Years. Per ClinicalTrials.gov, last updated 2019-03-27.
Sponsored by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins · Not applicable, Interventional, and Treatment
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.
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.
6,484 studies on the registry are indexed under Prostatic Neoplasms; 1,415 are open to participants now.
This study's enrollment of 2 is below the median of 58 across 4,908 interventional studies indexed under Prostatic Neoplasms.
Browse Prostatic Neoplasms studies →Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins is the lead sponsor of 582 studies on the registry; 72 are open to participants now.
Of its 113 completed or terminated interventional studies of FDA-regulated products, 67 (59%) have results posted.
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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:
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.
Drug: Lovastatin
oral qd varying dose escalations/de-escalations
Also known as: Altoprev®; Mevacor®
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.
Time frame: 1 year
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.
Time frame: 1 year
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.
Time frame: 1 year
Change in Cholesterol Level After Lovastatin Treatments.
Change in cholesterol level with each tested dose of oral lovastatin.
Time frame: 1 year
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.
Time frame: 1 year
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).
Time frame: 1 year
Study Compliance as Assessed by Number of Participants Who Follow All of the Study Rules.
Time frame: 1 year
Number of Participants With MYC Downregulation
Number of participants with MYC downregulation after high-dose lovastatin.
Time frame: 1 year
| Milestone | Lovastatin |
|---|---|
| Started | 2 |
| Completed | 1 |
| Not completed | 1 |
| Withdrew: Adverse event | 1 |
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.
| Participants | Lovastatin |
|---|---|
| Number of Participants That Can Achieve 60% MYC Modulation Response | 0 |
Toxicity of the different doses of continuous daily oral lovastatin in generally healthy men with prostate cancer prior to surgery.
No measurements were reported for this outcome.
Proportion of men with MYC target inhibition in prostate tumor tissue using paired tumor biopsies before and after lovastatin administration.
No measurements were reported for this outcome.
Change in cholesterol level with each tested dose of oral lovastatin.
No measurements were reported for this outcome.
Number of participants with target inhibition of MYC in relationship with pretreatment prostate biopsy Gleason sum, Ki-67, and degree of MYC overexpression.
No measurements were reported for this outcome.
Number of participants with target inhibition of MYC and markers of increased apoptosis (cleaved caspase-3) and proliferation (Ki-67).
No measurements were reported for this outcome.
No measurements were reported for this outcome.
Number of participants with MYC downregulation after high-dose lovastatin.
No measurements were reported for this outcome.
Collected over up to 1 year. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Lovastatin | 0/2 (0%) | 1/2 (50%) | 0/2 (0%) |
| Event | Lovastatin |
|---|---|
| rhabdomyolysisMusculoskeletal and connective tissue disorders | 1/2 |
| Age, Categorical(Participants) | Lovastatin |
|---|---|
| <=18 years | 0 |
| Between 18 and 65 years | 2 |
| >=65 years | 0 |
| Sex/Gender, Customized(Participants) | Lovastatin |
|---|---|
| Male | 2 |
| Region of Enrollment(Participants) | Lovastatin |
|---|---|
| United States | 2 |
Ran from Jul 2012 to primary completion in Apr 2013, 8 months.
Results were first posted in Nov 2015, 2 years 7 months after primary completion.
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This study is terminated, as verified in Mar 2019. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Lovastatin
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