Atorvastatin ± Aspirin in Lynch Syndrome Syndrome

NCT04379999 | Completed Early Phase 1 FDA Drug

• 1 other identifier: 18-1039
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this study is to investigate that a common cholesterol lowering agent (atorvastatin) alone or combining with a nonsteroidal anti-inflammatory drug (aspirin) would reduce the risk of colorectal cancer (CRC) in high-risk individuals with Lynch syndrome.

Conditions

Lynch Syndrome

Keywords

HNPCC; MLH1; MSH2; MSH6; PMS2; EPCAM; LYNCH

Outcome Measures

Primary Outcomes (2)

• Proliferation (Ki-67) and apoptosis (active caspase 3) by immunohistochemical staining

  Effect of Atorvastatin or/and Aspirin on normal colonic proliferation and apoptosis will be evaluated by comparing of immunohistochemical staining of Ki-67 and active caspase 3 using formalin-fixed paraffin-embedded biopsies collected before and at the 6 weeks of drug treatments. Number of positive cells and total number of evaluated cells will be collected for both assays. Data of cells with positive Ki-67 or active caspase 3 will be expressed as % of positive cells (# positive cells/#total evaluated cells x 100). Statistical analyses will be performed to compare the difference between baseline and 6-weeks data.

  Changes from baseline to 6 weeks

• Genome-wide expression analyses using RNA-Seq

  Effect of Atorvastatin or/and Aspirin on gene expressions in normal colonic epithelial cells will be analyzed using RNA-Seq. Total RNA will be extracted from frozen biopsies. RNASeq libraries will be generated and sequenced on an Illumina platform and analyzed. Differential expression between samples at baseline and 6-weeks of drug treatment will be assessed for statistical significance. Genes with false discovery rat ≤ 0.05 and a fold-change ≥ 2 will be considered significant.

  Changes from baseline to 6 weeks

Secondary Outcomes (3)

• Rate of adherence of healthy patients with Lynch Syndrome to a 6-week of the treatment regimen (atorvastatin ± aspirin).

  6 weeks

• Frequency of adverse events among patients administered atorvastatin ± aspirin for 6 weeks

  6 weeks

• Acceptability of the pilot study intervention and the willingness of the subject to participate in a similar larger study.

  6 weeks

Study Arms (2)

Atorvastatin

ACTIVE COMPARATOR

Atorvastatin (LIPITOR) 20 milligram tablet daily for 6 weeks

Drug: Atorvastatin 20mg

Atorvastatin and Aspirin

ACTIVE COMPARATOR

Atorvastatin (LIPITOR) 20 milligram tablet and Aspirin 325 mg tablet daily for 6 weeks

Drug: Atorvastatin 20mg AND Aspirin 325 mg

Interventions

Atorvastatin 20mg DRUG

No history of colorectal cancer and no colorectal adenomas within 5 years.

Also known as: Lipitor 20mg

Atorvastatin

Atorvastatin 20mg AND Aspirin 325 mg DRUG

History of colorectal cancer and/or history of colorectal adenomas within 5 years.

Also known as: Lipitor 20mg AND Aspirin 325mg

Atorvastatin and Aspirin

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects who are 18 years of age or older
• Able to read and sign an informed consent document in English
• Eligible subjects will have molecular evidence of Lynch Syndrome (mutation in MLH1, MSH2, MSH6, EPCAM or PMS2)
• History of colorectal cancer if surgically cured and \> 1 year from completion of adjuvant chemotherapy

You may not qualify if:

• Are \<18 years of age
• Unable to read and sign an informed consent document in English
• Have active cancer or are less than 3 years post hormonal maintenance therapy for cancer
• Have statin intolerance or contraindication for aspirin or atorvastatin use
• Are pregnant or are actively breast feeding

Sponsors & Collaborators

• Fox Chase Cancer Center: lead
• Prevent Cancer Foundation: collaborator

Study Sites (1)

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms, Hereditary Nonpolyposis

Interventions

Atorvastatin; Aspirin

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Neoplastic Syndromes, Hereditary; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Michael J Hall, MD, MS

  Fox Chase Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: One group receives atorvastatin 20 mg, and the other group receives atorvastatin 20 mg+ aspirin 325mg

Study Record Dates

• First Submitted: January 3, 2020
• First Posted: May 8, 2020
• Study Start: September 10, 2018
• Primary Completion: August 4, 2025
• Study Completion: August 4, 2025
• Last Updated: August 7, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Time Frame: beginning 9 months and ending 3 years following article publication
• Access Criteria: Investigators whose proposed use of data has been approved by a review committee identified for this purpose.Proposals should be directed to Michael.Hall@fccc.edu. To gain access, data requestors will need to sign a data access agreement.

Locations

US (1)