Pre-Prostatectomy Lovastatin on Prostate Cancer

This study has been terminated.
(The study was stopped due to an unanticipated serious adverse event.)
Sponsor:
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT01478828
First received: November 3, 2011
Last updated: April 9, 2013
Last verified: April 2013

November 3, 2011
April 9, 2013
March 2012
April 2013   (final data collection date for primary outcome measure)
Number of participants that can achieve 60% MYC modulation response [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
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.
Dose Determination [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
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.
Complete list of historical versions of study NCT01478828 on ClinicalTrials.gov Archive Site
  • Number of Participants who experience specific adverse events at different dosing points prior to surgery. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    6. To assess the study compliance.
  • Capture difference in MYC downregulation between treated participants and non-treated patients [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    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.
  • Number of Participants with Cholesterol Related Adverse Events [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    To assess the study compliance.
Not Provided
Not Provided
 
Pre-Prostatectomy Lovastatin on Prostate Cancer
Pharmacodynamic Trial of Pre-Prostatectomy Lovastatin on MYC (V-myc Myelocytomatosis Viral Oncogene Homolog) Down-Regulation in Localized Prostate Cancer

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.

Interventional
Not Provided
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Prostate Cancer
Drug: Lovastatin
oral qd varying dose escalations/de-escalations
Other Name: Altoprev®; Mevacor®
Not Provided
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
2
April 2013
April 2013   (final data collection date for primary outcome measure)

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.
Male
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01478828
J-1153, NA_00048234
Yes
Sidney Kimmel Comprehensive Cancer Center
Sidney Kimmel Comprehensive Cancer Center
Not Provided
Principal Investigator: Phouc Tran, M.D. Johns Hopkins University
Sidney Kimmel Comprehensive Cancer Center
April 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP