## Protocol Section
### Identification Module
**NCT ID:** NCT06437574

**Brief Title:** Intensive Cholesterol-Lowering and CD8+ T Cells in Prostate Cancer

**Official Title:** Lowering Cholesterol in Prostate Cancer to Target Rapamycin-Insensitive Companion Of MTOR (TORC2) in T-Cell Surface Glycoprotein CD8 Alpha Chain (CD8+) Lymphocytes

#### Organization Study ID Info
**ID:** STUDY00003290
#### Organization
**Class:** OTHER
**Full Name:** Cedars-Sinai Medical Center
#### Secondary ID Infos
**ID:** R01CA280060
**Link:** https://reporter.nih.gov/quickSearch/R01CA280060
**Type:** NIH
### Status Module
#### Completion Date
**Date:** 2028-05-31

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-31

**Type:** ESTIMATED

**Last Update Submit Date:** 2024-05-29

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2028-02-29

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-07-01

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-31
**Type:** ESTIMATED
**Study First Submit Date:** 2024-05-23
**Study First Submit QC Date:** 2024-05-29
### Sponsor Collaborators Module

#### Collaborators

**Class:** NIH

**Name:** National Cancer Institute (NCI)

#### Lead Sponsor

**Class:** OTHER

**Name:** Cedars-Sinai Medical Center

#### Responsible Party

**Investigator Affiliation:** Cedars-Sinai Medical Center

**Investigator Full Name:** Hyung L. Kim, MD

**Investigator Title:** Principal Investigator

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** True

**Is US Export:** True

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** To test the hypothesis that intensive cholesterol lowering (iCL) therapy has anti-tumor immune modulating activity, the investigators will conduct an open-label, single-arm phase II trial in prostate cancer patients who are in active surveillance and undergoing a planned surveillance biopsy in 3-6 months. Eligible patients will initiate iCL with Vytorin®(group 1, 2, and 3), an FDA-approved combination of ezetimibe and simvastatin used to lower atherogenic low density lipoprotein cholesterol (LDL-C) or Ezetimibe (group 4). Starting dose will be determined by current statin use and LDL-C levels. Dose modifications of VYTORIN will be employed with the goal of achieving LDL-C \<70 mg/dl. Dose adjustment is not allowed for ezetimibe.

### Conditions Module

**Conditions:**

- Prostate Cancer

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

##### Masking Info

**Masking:** NONE

**Primary Purpose:** PREVENTION

#### Enrollment Info

**Count:** 140

**Type:** ESTIMATED

**Phases:**

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Single arm with dual agents (ezetimibe and simvastatin) target the two primary sources of cholesterol, absorption in the gut and synthesis in the liver. These 2 agents are available in a single pill that is FDA approved and sold under the trade name, Vytorin.

**Intervention Names:**

- Drug: Vytorin

**Label:** Intensive Lipid Lowering

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Intensive Lipid Lowering

**Description:** Vytorin is a drug combination (Ezetimibe and Simvastatin) that targets the two primary sources of cholesterol, absorption in the gut and synthesis in the liver.

**Name:** Vytorin

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** Our primary hypothesis is that maximum cholesterol lowering will increase CD8+ memory T cells and increase CD8+ T cell infiltration into prostate tissue. Change in CD8+ T cells in the prostate from baseline to 3 to 6 months is the primary endpoint.

**Measure:** Pre/Post-change in % prostate infiltrating CD8+ T lymphocytes.

**Time Frame:** 3 to 6 months of cholesterol-lowering intervention

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

1. Provision of signed and dated informed consent form.
2. Stated willingness to comply with all study procedures and availability for the duration of the study.
3. At least one Atherosclerotic Cardiovascular Disease (ASCVD) risk factor, such as:

   1. ≥ 50 years of age
   2. Hypertension
   3. Hypercholesterolemia
   4. Diabetes
   5. Current or former smoker
   6. First-degree family history of any cardiovascular heart disease
   7. BMI \> 25
   8. On hypertension treatment, statin, and/or aspirin therapy
4. Patients with clinically localized prostate cancer. That is Low or intermediate risk prostate cancer deﬁned as:

   1. Pre-operative PSA (Prostate Specific Antigen) 20.0 ng/ml
   2. Clinical stage T1c or cT2
   3. Gleason score 3+3 or 3+4 or 4+3
5. Patients on AS with plans for surveillance biopsy
6. No previous treatment for prostate cancer with radiotherapy, chemotherapy, or hormonal therapy
7. Ability to take oral medication and be willing to adhere to once daily, oral Vytorin or ezetimibe.
8. Agree to avoid consumption of grapefruit and grapefruit juice ≥ one quart per day throughout study duration.

Exclusion Criteria:

1. Current use of medications contraindicated for use with a statin such as strong CYP3A4 inhibitors (e.g., itraconazole, ketoconazole, posaconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors, and nefazodone).
2. Current use of medications contraindicated for use with ezetimibe (i.e., gemfibrozil, cyclosporine, or danazol).
3. History of allergic or severe reaction to a either study agent.
4. History of moderate or severe myalgia with statin use.
5. Acute liver failure or decompensated cirrhosis
6. Already on maximum VYTORIN dose (10/80)
7. Already on a PCSK9 inhibitor

**Minimum Age:** 18 Years

**Sex:** MALE

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** Amy.Hoang@cshs.org

**Name:** Amy Hoang

**Phone:** 310-423-1542

**Role:** CONTACT

**Contact 2:**

**Email:** Laura.Sarmiento@cshs.org

**Name:** Laura Sarmiento

**Phone:** 310-423-4295

**Role:** CONTACT

#### Overall Officials

**Official 1:**

**Affiliation:** Cedars-Sinai Medical Center

**Name:** Hyung Kim, MD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000005834

- Term: Genital Neoplasms, Male

- ID: D000014565

- Term: Urogenital Neoplasms

- ID: D000009371

- Term: Neoplasms by Site

- ID: D000009369

- Term: Neoplasms

- ID: D000005832

- Term: Genital Diseases, Male

- ID: D000091662

- Term: Genital Diseases

- ID: D000091642

- Term: Urogenital Diseases

- ID: D000011469

- Term: Prostatic Diseases

- ID: D000052801

- Term: Male Urogenital Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: BXS

- Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions

- Abbrev: All

- Name: All Conditions

### Condition Browse Module - Browse Leaves

- ID: M14335

- Name: Prostatic Neoplasms

- Relevance: HIGH

- As Found: Prostate Cancer

- ID: M8946

- Name: Genital Neoplasms, Male

- Relevance: LOW

- As Found: Unknown

- ID: M17315

- Name: Urogenital Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M2876

- Name: Genital Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M8944

- Name: Genital Diseases, Male

- Relevance: LOW

- As Found: Unknown

- ID: M2875

- Name: Urogenital Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M14333

- Name: Prostatic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M27095

- Name: Male Urogenital Diseases

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000011471

- Term: Prostatic Neoplasms

### Intervention Browse Module - Ancestors

- ID: D000000924

- Term: Anticholesteremic Agents

- ID: D000000960

- Term: Hypolipidemic Agents

- ID: D000000963

- Term: Antimetabolites

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

- ID: D000057847

- Term: Lipid Regulating Agents

### Intervention Browse Module - Browse Branches

- Abbrev: Lipd

- Name: Lipid Regulating Agents

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: Infe

- Name: Anti-Infective Agents

- Abbrev: ANeo

- Name: Antineoplastic Agents

- Abbrev: Hemat

- Name: Hematinics

### Intervention Browse Module - Browse Leaves

- ID: M450

- Name: Ezetimibe, Simvastatin Drug Combination

- Relevance: HIGH

- As Found: Remdesivir

- ID: M21713

- Name: Simvastatin

- Relevance: LOW

- As Found: Unknown

- ID: M21960

- Name: Sirolimus

- Relevance: LOW

- As Found: Unknown

- ID: M11110

- Name: Liver Extracts

- Relevance: LOW

- As Found: Unknown

- ID: M409

- Name: Ezetimibe

- Relevance: LOW

- As Found: Unknown

- ID: M353695

- Name: Temsirolimus

- Relevance: LOW

- As Found: Unknown

- ID: M2827

- Name: MTOR Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M340819

- Name: polysaccharide-K

- Relevance: LOW

- As Found: Unknown

- ID: M4243

- Name: Anticholesteremic Agents

- Relevance: LOW

- As Found: Unknown

- ID: M4278

- Name: Hypolipidemic Agents

- Relevance: LOW

- As Found: Unknown

- ID: M4281

- Name: Antimetabolites

- Relevance: LOW

- As Found: Unknown

- ID: M28883

- Name: Lipid Regulating Agents

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000069499

- Term: Ezetimibe, Simvastatin Drug Combination

### Misc Info Module

- Version Holder: 2024-05-31
