Atorvastatin ± Aspirin in Lynch Syndrome Syndrome

Lynch Syndrome Clinical Trial

Official title:

Impact of Atorvastatin ± Aspirin on Colorectal Biomarkers in Patients With Lynch Syndrome: a Pilot Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04379999
• Other study ID #: 18-1039
• Status: Recruiting
• Phase: Early Phase 1
• Start date: September 10, 2018
• Est. completion date: September 10, 2023

Study information

• Verified date: April 2022
• Source: Fox Chase Cancer Center
• Contact: Yana Chertock, MA
• Phone: 215-214-3216
• Email: yana.chertock[@]fccc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

This is an exploratory biomarker trial to assess the ability of atorvastatin (common cholesterol lowering agent) alone or combining with aspirin (a nonsteroidal anti-inflammatory drug) to reduce the risk of colorectal cancer in high-risk individuals with Lynch Syndrome. Subjects will be stratified based on their prior history of polyps/cancer to receive atorvastatin without or with aspirin for 6 weeks. Blood and normal colon biopsies will be obtained at Day 0 and at 6 weeks on study. Tissue endpoints for analysis include cell proliferation, apoptosis and changes in gene expression. Circulating lipid profiles and metabolic function, and post-treatment questionnaires will be used to assess the acceptability of the study.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 46
• Est. completion date: September 10, 2023
• Est. primary completion date: September 1, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Colorectal Neoplasms, Hereditary Nonpolyposis
• Lynch Syndrome
• Syndrome

Intervention

Drug:
• Atorvastatin 20mg
No history of colorectal cancer and no colorectal adenomas within 5 years.
• Atorvastatin 20mg AND Aspirin 325 mg
History of colorectal cancer and/or history of colorectal adenomas within 5 years.

Locations

Country	Name	City	State
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Fox Chase Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Rate of adherence of healthy patients with Lynch Syndrome to a 6-week of the treatment regimen (atorvastatin ± aspirin).	Medication Adherence to the 6-week course of Atorvastatin or/and Aspirin preventive therapy will be assessed by one question in the follow -up survey which participants complete at the end of the study :"Over 6 weeks of preventive therapy, how many Atorvastatin/Aspirin pills did you forget to take?" In addition, participants will be asked to return medication bottle(s) with or without pills. RA will count pills and record number of missing pills in the system.	6 weeks
Secondary	Frequency of adverse events among patients administered atorvastatin ± aspirin for 6 weeks	The adverse event assessment form is used to collect initial and follow-up information for non-serious and serious adverse events for patients participating in the study. Participants are contacted by RA every two weeks to assess side effects and toxicity. A grading scale from 1 to 5 (1-mild, 2-moderate, 3-severy, 4-life-threatining, 5- death related to AE) and causality (1-unrelated, 2-unlikly, 3-possible, 4-probable, 5-definite, NA- not assessed) are recorded for each adverse event (AE) term. Each AE is reviewed by principal investigator and entered into patient's electronic medical record (EMR)	6 weeks
Secondary	Acceptability of the pilot study intervention and the willingness of the subject to participate in a similar larger study.	Acceptability of the study approach 6 Likert-type items (7 point scale) will assess participants' perceptions of various aspects of the study design as a measure of whether changes need to be made to the study methods or design prior to a larger multi-institutional trial. Participants' scores will be summed and a mean score generated. Mean scores > 4 will be considered in the acceptable range. Our threshold target is 75% of participants with a mean score in the acceptable range.	6 weeks