Testing Atorvastatin to Lower Colon Cancer Risk in Longstanding Ulcerative Colitis

• Status: Recruiting
• Trial end date: 2024-03-31
• Target enrollment: 0
• Participant gender: All

Summary

This phase II trial studies the effect of atorvastatin in treating patients with ulcerative colitis who have a dominant-negative missense P53 mutation and are at risk of developing large intestinal cancer. Patients with ulcerative colitis are known to have an increased risk of developing large intestinal cancer. Better ways to control ulcerative colitis and more knowledge about how to prevent colon cancer are needed. Atorvastatin is a drug used to lower the amount of cholesterol in the blood and to prevent stroke, heart attack, and angina (chest pain). It blocks an enzyme that helps make cholesterol in the body. It also causes an increase in the breakdown of cholesterol. The information gained from this study may help doctors learn more about atorvastatin as an agent in cancer prevention, and may help to improve public health.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Cancer Institute (NCI)
• Treatments: Atorvastatin; Calcium; Calcium, Dietary

Criteria

Inclusion Criteria:

• Participants must have ulcerative colitis with > 8 years history and clinical remission (including the clinical remission for an extraintestinal manifestation/complication) confirmed by yearly surveillance endoscopy examination (Mayo grading 0 or 1)

• They must be stable on maintenance therapy with mesalamine, thiopurines or biologics for over 3 months (Ulcerative Colitis Disease Activity Index [UCDAI] =< 1)

• A history of segmental colon resection is allowed

• UC in clinical remission, but with dysplasia-associated lesion or mass (DALM) at entry endoscope examination and DALM was completely resected by endoscopic mucosa resection, is allowed

• Participants 18-70 years old (both men and women). This is the standard age range for routine ulcerative colitis surveillance in adults

• Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)

• Absolute neutrophil count >= 1,500/uL

• Platelets >= 100,000/uL

• Total bilirubin within normal institutional limits, unless known to have Gilberts syndrome

• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (SGPT) =< 1.5 X institutional upper limit of normal (ULN)

• Creatinine =< 1.5 X institutional ULN

• International normalized ratio (INR) =< 1.5

• Plasma level of cholesterol < 240 mg/dl or LDL-C < 190 mg/dl (since cholesterol > 240 mg/dl and LDL-C > 190 mg/dl need high dose (40 - 80 mg) atorvastatin per day to control hypercholesterolemia)

• Atorvastatin is contraindicated in pregnancy since it affects cholesterol synthesis pathway. For this reason, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) from the time of baseline pregnancy test, throughout the duration of the study, and for 1 month following cessation of study drug. Females must begin adequate contraception immediately following screening pregnancy test. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately. If she is pregnant, she will be immediately withdrawn from the study and followed until the birth of the child

• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Ulcerative proctitis (since patients with ulcerative proctitis have a significantly lower risk of developing colorectal cancer [CRC] than those with pancolitis or localized UC in left colon)

• Subjects with medical conditions that, in the opinion of the investigator, would preclude the treatment intervention and colonoscopy, or limit ability to comply with therapy

• Subjects with pancolitis or localized UC with Mayo grading >= 2 are excluded

• Use of corticosteroid therapy in the past 3 months due to high potential of relapse of active disease

• Use of statins in the last 12 months

• Use of any investigational drugs within the past 3 months

• A history of high-grade dysplasia or CRC or pan/severe colitis with total proctocolectomy

• History of chemotherapy within 2 years of screening

• History of allergic reactions attributed to atorvastatin

• Concomitant primary sclerosing cholangitis (PSC) with stage 4 liver fibrosis and severe liver functional alteration

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

• Pregnant or lactating subjects are excluded

• Human immunodeficiency virus (HIV)-positive subjects are excluded due to anti-retroviral therapy that affect atorvastatin effect

• Children are excluded from this study since disease duration is usually < 8 years and there is no data about p53 mutation in this patient population

• Current use of cyclosporine, fibrates (e.g., gemfibrozil, fenofibrate), strong CYP3A4 inhibitors (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, human immunodeficiency virus (HIV) protease inhibitors, boceprevir, telaprevir, erythromycin, clarithromycin, telithromycin, nefazodone, or cobicistat-containing products), or strong CYP3A4 inducers (e.g., carbamazepine, phenytoin, rifampin, St. John's wort, bosentan, efavirenz, etravirine, modafinil, nafcillin)