Testing Atorvastatin to Lower Colon Cancer Risk in Longstanding Ulcerative Colitis

January 20, 2026 updated by: Northwestern University

A Randomized and Placebo-Controlled Phase II Trial Targeting Dominant-Negative Missense Mutant P53 by Atorvastatin for Reducing the Risk of Longstanding Ulcerative Colitis-Associated Cancer

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

PRIMARY OBJECTIVE:

I. To determine the effect of atorvastatin calcium (atorvastatin) treatment on reducing the fraction of colonic epithelial cells expressing mutant p53 protein detected via immunohistochemical staining in biopsy samples of colorectal mucosa obtained during colonoscopies done before and after atorvastatin intervention and compared to placebo control.

SECONDARY OBJECTIVES:

I. Examination of the effect of atorvastatin on the levels of biomarkers including Ki-67 (cell proliferation), Waf1p21 (wild type p53 allele reactivated signal), and cleaved caspase-3 (wild type p53-induced cell apoptosis) using immunohistochemistry (IHC) approach for colorectal biopsy specimens.

II. Examination of the effect of atorvastatin on the severity of histologic inflammation in colorectal biopsies using the Geboes grading system.

III. Examination of the effect of atorvastatin on the plasma concentration of cholesterol, high density lipoprotein (HDL) and low density lipoprotein (LDL) for monitoring atorvastatin effect on lowering cholesterol and its correlation with the levels of biomarkers in the colorectal biopsies.

IV. Examination of the effect of atorvastatin on the clinical efficacy on ulcerative colitis (UC) related symptoms using the Ulcerative Colitis Disease Activity Index (i.e. the Mayo score).

EXPLORATORY OBJECTIVES I. Examination of the effect of atorvastatin on the spectrum, hotspot and load of TP53 gene mutations using next generation sequencing and droplet digital polymerase chain reaction (PCR).

II. Will bank colorectal biopsies and blood samples and ribonucleic acid (RNA) and germline deoxyribonucleic acid (DNA) for future analyses, particularly on proteomics/prenylated protein profile, cytokine/chemokine profile, inflammatory lipid-mediator profile, RNA sequencing (RNAseq) and Chaperon/Co-chaperon proteins, etc.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive atorvastatin orally (PO) once daily (QD) for 12 months. Patients also undergo colonoscopy with biopsy, and collection of blood on the trial.

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

After completion of study treatment, patients are followed up at 2 weeks.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
42

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University
      • Chicago, Illinois, United States, 60637
        • University of Chicago Comprehensive Cancer Center
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • University of Kansas Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 66 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 < 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
  • 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)
  • 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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Arm I (atorvastatin, biospecimen collection)
Patients receive atorvastatin PO QD for 12 months. Patients also undergo colonoscopy with biopsy, and collection of blood on the trial.
Other: Questionnaire Administration
Ancillary studies
Procedure: Biospecimen Collection
Undergo collection of blood samples
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
Drug: Atorvastatin Calcium
Given PO
Other Names:
  • Lipitor
  • CI-981
  • ATORVASTATIN CALCIUM TRIHYDRATE
Procedure: Biopsy of Colon
Undergo colonoscopy with biopsy
Other Names:
  • Colonoscopic Biopsy
  • Colonoscopy and Biopsy
Placebo Comparator: Arm II (placebo, biospecimen collection)
Patients receive placebo PO QD for 12 months. Patients also undergo colonoscopy with biopsy, and collection of blood on the trial.
Other: Questionnaire Administration
Ancillary studies
Procedure: Biospecimen Collection
Undergo collection of blood samples
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
Drug: Placebo Administration
Given PO
Procedure: Biopsy of Colon
Undergo colonoscopy with biopsy
Other Names:
  • Colonoscopic Biopsy
  • Colonoscopy and Biopsy

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Reduction in mutant p53 staining in biopsy samples obtained during colonoscopies done before and after intervention
Time Frame: Up to 2 years
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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)
Time Frame: Up to 2 years
Using IHC approach for colorectal biopsy specimens.
Up to 2 years
Histological analysis for grading the severity of histologic inflammation in colorectal biopsies
Time Frame: Up to 2 years
Using the Geboes grading system (grading score: 0 - 4). Highest grade histology and extent of UC (pancolitis vs localized UC) across multiple samples will be used at each time point. Changes in scores from baseline to post-treatment will be calculated, and compared between arms using the Wilcoxon rank sum test.
Up to 2 years
Plasma concentration of cholesterol, high density lipoprotein (HDL) and low density lipoprotein (LDL)
Time Frame: Up to 2 years
Will monitor atorvastatin effect on lowering cholesterol and its correlation with the levels of biomarkers in the colorectal biopsies. Changes in plasma concentration of cholesterol, HDL and LDL (for monitoring atorvastatin effect on lowering cholesterol) will be compared between treatment arms using similar approaches as the primary analysis of %TP53 described above. The association of plasma concentration of cholesterol, HDL and LDL with the levels of biomarkers in the colorectal biopsies will be analyzed using linear mixed models as described above with plasma level added to the model as a fixed effect. Separate models will be fitted for each type of cholesterol (total, HDL and LDL).
Up to 2 years
Clinical efficacy on UC related symptoms
Time Frame: Up to 2 years
Using the Ulcerative Colitis Disease Activity Index (activity score: 0 - 4) (i.e. the Mayo score).
Up to 2 years

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Analysis of spectrum, hotspot and load of TP53 gene mutations
Time Frame: Up to 2 years
Using next generation sequencing and droplet digital polymerase chain reaction (PCR) technologies. The spectrum of TP53 mutations will be analyzed for frequency of each hotspot mutation in each group. For analyzing binary variables (presence or absence of each hot spot mutation), a Pearson's chi-squared test will be used. Frequency of each hotspot mutation for each noted group will be provided as descriptive measures of location and variance. The load of TP53 mutations in the biopsy specimens will be quantified as the ratio of mutant allele to wild-type allele using droplet digital PCR and allele-specific primers. Descriptive statistics will be used to summarize these at each time point for each treatment arm. Changes in TP53 mutation load, a continuous biomarker, will be compared between treatment arms using similar approaches as the primary analysis of %TP53 described above.
Up to 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Northwestern University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Cancer Institute (NCI)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Stephen B Hanauer, MD, Northwestern University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 24, 2021

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 4, 2025

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 30, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 23, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 23, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 24, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 21, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 20, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • NCI 20-02-02
  • P30CA060553 (U.S. NIH Grant/Contract)
  • UG1CA242643 (U.S. NIH Grant/Contract)
  • NCI-2021-01261 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • NCI20-02-02 (Other Identifier: Northwestern University)
  • NWU20-02-02 (Other Identifier: DCP)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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