Pre-Prostatectomy Lovastatin on Prostate Cancer

Tracking Information
First Submitted Date ICMJE	November 3, 2011
First Posted Date ICMJE	November 23, 2011
Results First Submitted Date	January 13, 2015
Results First Posted Date	November 9, 2015
Last Update Posted Date	November 9, 2015
Study Start Date ICMJE	March 2012
Actual Primary Completion Date	April 2013 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: April 6, 2012)	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.
Original Primary Outcome Measures ICMJE; (submitted: November 21, 2011)	Dose Determination [ 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.
Change History	Complete list of historical versions of study NCT01478828 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: April 6, 2012)	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.
Original Secondary Outcome Measures ICMJE; (submitted: November 21, 2011)	Number of Participants with Cholesterol Related Adverse Events [ Time Frame: 1 year ]To characterize the effect of continuous daily oral lovastatin on cholesterol level in this patient population, at the doses tested in this trial.; Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 1 year ]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.; Pharmacodynamics [ Time Frame: 1 year ]To assess the relationship of pharmacodynamic target inhibition of MYC with pretreatment prostate biopsy Gleason sum, Ki-67, and degree of MYC overexpression.; Target Inhibition [ Time Frame: 1 year ]To assess an association of pharmacodynamic target inhibition of MYC with markers of increased apoptosis (cleaved caspase-3) and proliferation (Ki-67).; Study Compliance [ Time Frame: 1 year ]To assess the study compliance.
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Pre-Prostatectomy Lovastatin on Prostate Cancer
Official Title ICMJE	Pharmacodynamic Trial of Pre-Prostatectomy Lovastatin on MYC (V-myc Myelocytomatosis Viral Oncogene Homolog) Down-Regulation in Localized Prostate Cancer
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.
Study Type ICMJE	Interventional
Study Phase	Not Applicable
Study Design ICMJE	Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Prostate Cancer
Intervention ICMJE	Drug: Lovastatin; oral qd varying dose escalations/de-escalations; Other Name: Altoprev®; Mevacor®
Study Arms	Experimental: Lovastatin; 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: Drug: Lovastatin
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Suspended
Actual Enrollment ICMJE; (submitted: April 9, 2013)	2
Original Estimated Enrollment ICMJE; (submitted: November 21, 2011)	25
Estimated Study Completion Date	April 2016
Actual Primary Completion Date	April 2013 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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.
Sex/Gender	Sexes Eligible for Study: Male
Ages	18 Years to 100 Years (Adult, Older Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01478828
Other Study ID Numbers ICMJE	J-1153; NA_00048234 ( Other Identifier: Johns Hopkins University School of Medicine )
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study Sponsor ICMJE	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators ICMJE	Not Provided
Investigators ICMJE	Principal Investigator: Phouc Tran, M.D. Johns Hopkins University
PRS Account	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Verification Date	October 2015
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP