Testing Atorvastatin to Lower Colon Cancer Risk in Longstanding Ulcerative Colitis

NCT04767984 | Active Not Recruiting Phase 2 DMC FDA Drug

• 6 other identifiers: NCI 20-02-02P30CA060553UG1CA242643NCI-2021-01261NCI20-02-02NWU20-02-02
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Ulcerative Colitis; Colorectal Carcinoma

Outcome Measures

Primary Outcomes (1)

• Reduction in mutant p53 staining in biopsy samples obtained during colonoscopies done before and after intervention

  Counted as p53 positive cells/100 epithelial cells under at least 5 high powered fields per slide or 100 crypts or 2000 cells/slide per biopsy, measured by immunohistochemistry (IHC) staining. The level of biomarker expression will be determined by chromogenic staining. Because multiple samples will be obtained per participant, participant-level %p53 mutation will be summarized as the average %p53 across these samples. Descriptive statistics will be used to summarize changes in each arm, as well as the difference in change between arms. Analysis will be conducted using a two-sample t-test comparing within-subject changes in average percentage (%) p53 between treatment arms. A more comprehensive analysis will be done using a linear mixed effects model, where the outcome variable will be %p53 staining in each sample evaluated at baseline and post-treatment.

  Up to 2 years

Secondary Outcomes (4)

• Levels of biomarkers of Ki-67 (cell proliferation), Waf1p21 (wild type p53 allele reactivated signal), and cleaved caspase-3 (wild type p53-induced cell apoptosis)

  Up to 2 years

• Histological analysis for grading the severity of histologic inflammation in colorectal biopsies

  Up to 2 years

• Plasma concentration of cholesterol, high density lipoprotein (HDL) and low density lipoprotein (LDL)

  Up to 2 years

• Clinical efficacy on UC related symptoms

  Up to 2 years

Other Outcomes (1)

• Analysis of spectrum, hotspot and load of TP53 gene mutations

  Up to 2 years

Study Arms (2)

Arm I (atorvastatin, biospecimen collection)

EXPERIMENTAL

Patients receive atorvastatin PO QD for 12 months. Patients also undergo colonoscopy with biopsy, and collection of blood on the trial.

Drug: Atorvastatin Calcium; Procedure: Biopsy of Colon; Procedure: Biospecimen Collection; Other: Questionnaire Administration

Arm II (placebo, biospecimen collection)

PLACEBO COMPARATOR

Patients receive placebo PO QD for 12 months. Patients also undergo colonoscopy with biopsy, and collection of blood on the trial.

Procedure: Biopsy of Colon; Procedure: Biospecimen Collection; Drug: Placebo Administration; Other: Questionnaire Administration

Interventions

Atorvastatin Calcium DRUG

Given PO

Also known as: ATORVASTATIN CALCIUM TRIHYDRATE, CI-981, Lipitor

Arm I (atorvastatin, biospecimen collection)

Biopsy of Colon PROCEDURE

Undergo colonoscopy with biopsy

Also known as: Colonoscopic Biopsy, Colonoscopy and Biopsy

Arm I (atorvastatin, biospecimen collection); Arm II (placebo, biospecimen collection)

Biospecimen Collection PROCEDURE

Undergo collection of blood samples

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Arm I (atorvastatin, biospecimen collection); Arm II (placebo, biospecimen collection)

Placebo Administration DRUG

Given PO

Arm II (placebo, biospecimen collection)

Questionnaire Administration OTHER

Ancillary studies

Arm I (atorvastatin, biospecimen collection); Arm II (placebo, biospecimen collection)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 \< 3)
• 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 =\< 2 (Karnofsky \>= 60%)
• White blood cell count within normal institutional limits or 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
• 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)
• For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
• Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
• Participants on chronic suppressive antiviral therapy for herpes simplex virus (HSV) are eligible

You may not qualify if:

• 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)
• Participants with medical conditions that, in the opinion of the investigator, would preclude the treatment intervention and colonoscopy, or limit ability to comply with therapy
• Participants with pancolitis or localized UC with total Mayo score \>= 3 including Mayo endoscopic sub-score \< 3 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 (biliary cirrhosis) and severe liver functional alteration
• Uncontrolled intercurrent illness or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant or breastfeeding participants are excluded
• Human immunodeficiency virus (HIV)-positive participants 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)

Sponsors & Collaborators

• Northwestern University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

University of Kansas Cancer Center

Kansas City, Kansas, 66160, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Colitis, Ulcerative

Interventions

Atorvastatin; Colonoscopy; Biopsy; Specimen Handling

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Colitis; Gastroenteritis; Inflammatory Bowel Diseases

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids; Endoscopy, Gastrointestinal; Endoscopy, Digestive System; Diagnostic Techniques, Digestive System; Diagnostic Techniques and Procedures; Diagnosis; Endoscopy; Diagnostic Techniques, Surgical; Digestive System Surgical Procedures; Surgical Procedures, Operative; Minimally Invasive Surgical Procedures; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Investigative Techniques

Study Officials

• Stephen B Hanauer, MD

  Northwestern University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 23, 2021
• First Posted: February 24, 2021
• Study Start: September 24, 2021
• Primary Completion: December 4, 2025
• Study Completion (Estimated): November 30, 2026
• Last Updated: January 21, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share

Locations

US (3)