Prostate CancerEarly Phase 1NCT02534376
Cellular Effect of Cholesterol-Lowering Prior to Prostate Removal
A Early Phase 1 study testing ezetimibe 10mg-simvastatin 40mg in people with Prostate Cancer, run by Cedars-Sinai Medical Center at 1 site in United States.
Trial summary
There is evidence in human studies as well as animal studies that treatments to lower cholesterol can reduce the risk of dying from prostate cancer.To decide if cholesterol-lowering therapy can slow the growth of prostate cancer, the investigators would like to lower cholesterol prior to surgery and then measure the… Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostate Cancer
- What is being tested?
- ezetimibe 10mg-simvastatin 40mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 63 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2015to 28 Feb 2019
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Biopsy containing ≥ 10 tissue cores sampled
- Biopsy positive for adenocarcinoma of the prostate containing any quantity of Gleason 3 component (e.g. Gleason score 3+3, 3+4, 4+3)
- Scheduled to undergo robotic radical prostatectomy
- Serum Prostate-Specific Antigen (PSA) <20 ng/ml
- Ability to understand and the willingness to sign a written informed consent
Who cannot join
- Pharmacologic therapy (e.g. statins or ezetimibe) to lower cholesterol within 30 days prior to registration.
- Prior treatment for CaP by surgery, irradiation, local ablative (e.g. cryosurgery or high intensity focused ultrasound) or androgen deprivation therapy.
- 5-alpha reductase inhibitors (e.g. finasteride or dutasteride) within 180 days prior to registration.
- Hypersensitivity to simvastatin or ezetimibe.
- Pharmacologic therapy with agents reported to produce adverse drug-drug interactions. (Table 2)
Trial locations and contacts
1 site in 1 country.
United States1 site
Cedars Sinai Medical Center
Los Angeles, California, 90048
About this study
Official title: Phase 0 Trial of Presurgical Cholesterol-lowering on Prostate Cancer Cell Growth
There is evidence in human studies as well as animal studies that treatments to lower cholesterol can reduce the risk of dying from prostate cancer.To decide if cholesterol-lowering therapy can slow the growth of prostate cancer, the investigators would like to lower cholesterol prior to surgery and then measure the growth of prostate cancers cells when the prostate has been removed. The investigators will use the combination of two drugs that is approved by the U.S. Food and Drug Administration to lower cholesterol. The drug combination is commercially available with a doctor's prescription and sold as Vytorin®. It is known that maximal cholesterol-lower effects are seen after 2 weeks of treatment with Vytorin®. Therefore, study patients receive at least 2 weeks, but no more than 6 weeks of Vytorin® prior to surgery.
Read the detailed description
BACKGROUND AND RATIONALE
Prostate cancer is the most commonly diagnosed cancer and the second leading cause of cancer death among men in North America. In the US, there are more than 200,000 newly diagnosed cases and nearly 40,000 deaths from prostate cancer (CaP) annually. Although elevated lipid levels are understood to increase risk of coronary heart disease, their importance for CaP is not understood. Epidemiologic studies consistently show an association between lipid lowering interventions and decreased risk of advanced CaP. There are no reports of prospective studies of lipid-lowering interventions directed at CaP.
Epidemiologic studies and preclinical observations suggest that interventions to lower cholesterol will decrease the risk of developing lethal CaP. However, a definitive, phase III study of cholesterol-lowering effects on advanced CaP development is needed prior to clinical implementation of this intervention. Such a trial will require a massive commitment of resources for the large number of patients needing long follow-up. A rational intermediate step is to conduct a presurgical intervention study to lower cholesterol in men undergoing radical prostatectomy. Molecular evidence of treatment effect will provide a sound rationale for definitive clinical trials, and may provide predictive biomarkers that can be validated in these future trials.
The investigators propose a prospective trial to assess the effects on the human prostate of a maximal cholesterol lowering strategy using dual agents in men already scheduled to undergo radical prostatectomy for prostate cancer.
Simvastatin is a cholesterol-lowering drug approved by the FDA in 1991 and is now commercially available as Zocor (Merck) or as a generic agent. After ingestion, it is converted from an inactive lactone to the corresponding β-hydroxyacid, which inhibits HMG-CoA reductase and the conversion of HMG-CoA to mevalonate. Ezetimibe is a cholesterol-lowering agent that operates by a distinct mechanism from HMG-CoA reductase inhibitors. It was FDA approved in 2002 and is commonly administered alone or in combination with a statin. It specifically inhibits a cholesterol transporter in the small intestines and selectively inhibits the absorption of cholesterol and related sterols.
A single pill that combines simvastatin and ezetimibe is available from Merck (Vytorin). This commercially available agent at its standard dose is used in this trial. This study uses the combination of simvastatin and ezetimibe to achieve maximal cholesterol lowering prior to prostatectomy.
- Conditions
- Prostate Cancer
- Being tested
- ezetimibe 10mg-simvastatin 40mg
- Keywords
- prostatectomy, cholesterol, statin
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ezetimibe 10mg-simvastatin 40mgDrug
Also called Vytorin
Vytorin (ezetimibe 10mg-simvastatin 40mg) will be given on an outpatient basis. The drug will be taken orally each day until the subject undergoes radical prostatectomy. The start of Vytorin is timed so that patients get the last dose the day before surgery. Subjects receive a two to four weeks of Vytorin.
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | Vytorin (ezetimibe 10mg-simvastatin 40mg) Receives: Drug: ezetimibe 10mg-simvastatin 40mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Growth of Gleason grade 3 prostate cancer
Prostate tissue removed at the time of surgery will be examined to measure cellular growth using molecular assays.
Measured: following 2-6 weeks of cholesterol lowering intervention.
Secondary outcomes (2)
Growth of benign prostate glands
Prostate tissue removed at the time of surgery will be examined to measure cellular growth using molecular assays.
Measured: following 2-6 weeks of cholesterol lowering intervention.
Growth of high grade prostate cancer (e.g. Gleason grade 4/5)
Prostate tissue removed at the time of surgery will be examined to measure cellular growth using molecular assays.
Measured: following 2-6 weeks of cholesterol lowering intervention.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Aug 2015 (estimated)
- Study startSep 2015
- Primary completion28 Feb 2019
- Study completion28 Feb 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- More trials run by Cedars-Sinai Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 63 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cedars-Sinai Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Roswell Park Cancer Institute
- Responsible party
- Principal investigator, Hyung L. Kim, MD, Cedars-Sinai Medical Center
- Investigators
- Hyung L Kim, MD, Principal investigator, Cedars-Sinai Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02534376
- Sponsor's protocol ID
- Pro00040945
- Status last verified
- Feb 2023
- First submitted
- 25 Aug 2015
- Last updated
- 22 Feb 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 0 Trial of Presurgical Cholesterol-lowering on Prostate Cancer Cell Growth
- ClinicalTrials.gov ID
- NCT02534376
- Acronym / sponsor ID
- Pro00040945
- Conditions
- Prostate Cancer
- Keywords
- prostatectomy, cholesterol, statin
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 63 participants (actual)
- Lead sponsor
- Cedars-Sinai Medical CenterUniversity, hospital or other
- Collaborators
- Roswell Park Cancer Institute
- Study start
- Sep 2015 (actual)
- Primary completion
- 28 Feb 2019 (actual)
- Study completion
- 28 Feb 2019 (actual)
- First posted
- 27 Aug 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
There is evidence in human studies as well as animal studies that treatments to lower cholesterol can reduce the risk of dying from prostate cancer.To decide if cholesterol-lowering therapy can slow the growth of prostate cancer, the investigators would like to lower cholesterol prior to surgery and then measure the growth of prostate cancers cells when the prostate has been removed. The investigators will use the combination of two drugs that is approved by the U.S. Food and Drug Administration to lower cholesterol. The drug combination is commercially available with a doctor's prescription and sold as Vytorin®. It is known that maximal cholesterol-lower effects are seen after 2 weeks of treatment with Vytorin®. Therefore, study patients receive at least 2 weeks, but no more than 6 weeks of Vytorin® prior to surgery.
Detailed description
BACKGROUND AND RATIONALE
Prostate cancer is the most commonly diagnosed cancer and the second leading cause of cancer death among men in North America. In the US, there are more than 200,000 newly diagnosed cases and nearly 40,000 deaths from prostate cancer (CaP) annually. Although elevated lipid levels are understood to increase risk of coronary heart disease, their importance for CaP is not understood. Epidemiologic studies consistently show an association between lipid lowering interventions and decreased risk of advanced CaP. There are no reports of prospective studies of lipid-lowering interventions directed at CaP.
Epidemiologic studies and preclinical observations suggest that interventions to lower cholesterol will decrease the risk of developing lethal CaP. However, a definitive, phase III study of cholesterol-lowering effects on advanced CaP development is needed prior to clinical implementation of this intervention. Such a trial will require a massive commitment of resources for the large number of patients needing long follow-up. A rational intermediate step is to conduct a presurgical intervention study to lower cholesterol in men undergoing radical prostatectomy. Molecular evidence of treatment effect will provide a sound rationale for definitive clinical trials, and may provide predictive biomarkers that can be validated in these future trials.
The investigators propose a prospective trial to assess the effects on the human prostate of a maximal cholesterol lowering strategy using dual agents in men already scheduled to undergo radical prostatectomy for prostate cancer.
Simvastatin is a cholesterol-lowering drug approved by the FDA in 1991 and is now commercially available as Zocor (Merck) or as a generic agent. After ingestion, it is converted from an inactive lactone to the corresponding β-hydroxyacid, which inhibits HMG-CoA reductase and the conversion of HMG-CoA to mevalonate. Ezetimibe is a cholesterol-lowering agent that operates by a distinct mechanism from HMG-CoA reductase inhibitors. It was FDA approved in 2002 and is commonly administered alone or in combination with a statin. It specifically inhibits a cholesterol transporter in the small intestines and selectively inhibits the absorption of cholesterol and related sterols.
A single pill that combines simvastatin and ezetimibe is available from Merck (Vytorin). This commercially available agent at its standard dose is used in this trial. This study uses the combination of simvastatin and ezetimibe to achieve maximal cholesterol lowering prior to prostatectomy.
Study design
- Primary purpose
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Drug: ezetimibe 10mg-simvastatin 40mgVytorin (ezetimibe 10mg-simvastatin 40mg) |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Biopsy containing ≥ 10 tissue cores sampled
- Biopsy positive for adenocarcinoma of the prostate containing any quantity of Gleason 3 component (e.g. Gleason score 3+3, 3+4, 4+3)
- Scheduled to undergo robotic radical prostatectomy
- Serum Prostate-Specific Antigen (PSA) <20 ng/ml
- Ability to understand and the willingness to sign a written informed consent
Key exclusion criteria (5 listed)
- Pharmacologic therapy (e.g. statins or ezetimibe) to lower cholesterol within 30 days prior to registration.
- Prior treatment for CaP by surgery, irradiation, local ablative (e.g. cryosurgery or high intensity focused ultrasound) or androgen deprivation therapy.
- 5-alpha reductase inhibitors (e.g. finasteride or dutasteride) within 180 days prior to registration.
- Hypersensitivity to simvastatin or ezetimibe.
- Pharmacologic therapy with agents reported to produce adverse drug-drug interactions. (Table 2)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ezetimibe 10mg-simvastatin 40mgAlso: VytorinVytorin (ezetimibe 10mg-simvastatin 40mg) will be given on an outpatient basis. The drug will be taken orally each day until the subject undergoes radical prostatectomy. The start of Vytorin is timed so that patients get the last dose the day before surgery. Subjects receive a two to four weeks of Vytorin. | Drug | Treatment |
Primary outcome
Growth of Gleason grade 3 prostate cancer
Time frame: following 2-6 weeks of cholesterol lowering intervention.
Prostate tissue removed at the time of surgery will be examined to measure cellular growth using molecular assays.
2 secondary outcomes
Growth of benign prostate glands
Time frame: following 2-6 weeks of cholesterol lowering intervention.
Growth of high grade prostate cancer (e.g. Gleason grade 4/5)
Time frame: following 2-6 weeks of cholesterol lowering intervention.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Feb 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hyung L Kim, MD principal investigator
Cedars-Sinai Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing ezetimibe 10mg-simvastatin 40mg in people with Prostate Cancer, run by Cedars-Sinai Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Growth of Gleason grade 3 prostate cancer (time frame: following 2-6 weeks of cholesterol lowering intervention.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Feb 2023.