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Colorectal CarcinomaPhase 2NCT04767984

Testing Atorvastatin to Lower Colon Cancer Risk in Longstanding Ulcerative Colitis

A Phase 2 study testing Atorvastatin Calcium, Biopsy of Colon and Biospecimen Collection in people with Colorectal Carcinoma and Ulcerative Colitis, run by Northwestern University at 3 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Colorectal Carcinoma, Ulcerative Colitis
What is being tested?
Atorvastatin Calcium, Biopsy of Colon and Biospecimen Collection
Type of treatment
Surgery or procedure
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
42 participants
Where
3 sitesUnited States
Study dates
24 Sep 2021to 30 Nov 2026
Phase
Phase 2
Are there results?
Not yet: the study is under way

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 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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%)
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  • 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

Who cannot join

  • 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
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  • 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)

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Northwestern University

    Chicago, Illinois, 60611

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

  • University of Kansas Cancer Center

    Kansas City, Kansas, 66160

Other trials in United States

About this study

Official title: 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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. 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:

  1. 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.

Being tested
Atorvastatin Calcium, Biopsy of Colon, Biospecimen Collection, Placebo Administration, Questionnaire Administration
Medical subject headings
Colorectal Neoplasms, Colitis, Ulcerative

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Atorvastatin CalciumDrug

    Also called ATORVASTATIN CALCIUM TRIHYDRATE, CI-981, Lipitor

    Given PO

  • Biopsy of ColonProcedure or surgery

    Also called Colonoscopic Biopsy, Colonoscopy and Biopsy

    Undergo colonoscopy with biopsy

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection

    Undergo collection of blood samples

  • Placebo AdministrationDrug

    Given PO

  • Questionnaire AdministrationOther

    Ancillary studies

Study groups in NCT04767984
Study groupRoleWhat they receive
Arm I (atorvastatin, biospecimen collection)ExperimentalPatients receive atorvastatin PO QD for 12 months. Patients also undergo colonoscopy with biopsy, and collection of blood on the trial.
Receives: Drug: Atorvastatin Calcium; Procedure: Biopsy of Colon; Procedure: Biospecimen Collection; Other: Questionnaire Administration
Arm II (placebo, biospecimen collection)Placebo comparatorPatients receive placebo PO QD for 12 months. Patients also undergo colonoscopy with biopsy, and collection of blood on the trial.
Receives: Procedure: Biopsy of Colon; Procedure: Biospecimen Collection; Drug: Placebo Administration; Other: Questionnaire Administration

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Up to 2 years

Secondary outcomes (4)

  1. 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)

    Using IHC approach for colorectal biopsy specimens.

    Measured: Up to 2 years

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

    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.

    Measured: Up to 2 years

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

    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).

    Measured: Up to 2 years

  4. Clinical efficacy on UC related symptoms

    Using the Ulcerative Colitis Disease Activity Index (activity score: 0 - 4) (i.e. the Mayo score).

    Measured: Up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Feb 2021
  2. Study start24 Sep 2021
  3. Primary completion4 Dec 2025
  4. Study completion30 Nov 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
42 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04767984
Sponsor's protocol ID
NCI 20-02-02
Other IDs
P30CA060553, UG1CA242643, NCI-2021-01261, NCI20-02-02, NWU20-02-02
Status last verified
Jan 2026
First submitted
23 Feb 2021
Last updated
21 Jan 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Atorvastatin Calcium, Biopsy of Colon and Biospecimen Collection in people with Colorectal Carcinoma and Ulcerative Colitis, run by Northwestern University at 3 sites 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 17 inclusion and 15 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: under way, not looking for participants, as of the sponsor's last update on 21 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites 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. Some participants in this study may receive a placebo. 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?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

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?

Reduction in mutant p53 staining in biopsy samples obtained during colonoscopies done before and after intervention (time frame: Up to 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04767984.

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 21 Jan 2026; AzTrials last refreshed its copy on 6 Nov 2026.

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