Lynch SyndromeEarly Phase 1NCT04379999
Atorvastatin ± Aspirin in Lynch Syndrome Syndrome
A Early Phase 1 study testing Atorvastatin 20mg and Atorvastatin 20mg AND Aspirin 325 mg in people with Lynch Syndrome, run by Fox Chase Cancer Center at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Lynch Syndrome
- What is being tested?
- Atorvastatin 20mg and Atorvastatin 20mg AND Aspirin 325 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 43 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Sep 2018to 4 Aug 2025
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
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 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
About this study
Official title: Impact of Atorvastatin ± Aspirin on Colorectal Biomarkers in Patients With Lynch Syndrome: a Pilot Study
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.
Read the detailed 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.
- Conditions
- Lynch Syndrome
- Being tested
- Atorvastatin 20mg, Atorvastatin 20mg AND Aspirin 325 mg
- Keywords
- HNPCC, MLH1, MSH2, MSH6, PMS2, EPCAM, LYNCH
- Medical subject headings
- Colorectal Neoplasms, Hereditary Nonpolyposis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Atorvastatin 20mgDrug
Also called Lipitor 20mg
No history of colorectal cancer and no colorectal adenomas within 5 years.
Atorvastatin 20mg AND Aspirin 325 mgDrug
Also called Lipitor 20mg AND Aspirin 325mg
History of colorectal cancer and/or history of colorectal adenomas within 5 years.
| Study group | Role | What they receive |
|---|---|---|
| Atorvastatin | Active comparator | Atorvastatin (LIPITOR) 20 milligram tablet daily for 6 weeks Receives: Drug: Atorvastatin 20mg |
| Atorvastatin and Aspirin | Active comparator | Atorvastatin (LIPITOR) 20 milligram tablet and Aspirin 325 mg tablet daily for 6 weeks Receives: Drug: Atorvastatin 20mg AND Aspirin 325 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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).
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.
Measured: 6 weeks
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)
Measured: 6 weeks
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.
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 May 2020
- Study start10 Sep 2018
- Primary completion4 Aug 2025
- Study completion4 Aug 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lynch SyndromeStudies of the same condition, open and under way.
- More trials run by Fox Chase Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- One group receives atorvastatin 20 mg, and the other group receives atorvastatin 20 mg+ aspirin 325mg
- Masking
- None (open label)
- Enrolment
- 43 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fox Chase Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Prevent Cancer Foundation
- Responsible party
- Sponsor
- Investigators
- Michael J Hall, MD, MS, Principal investigator, Fox Chase Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04379999
- Sponsor's protocol ID
- 18-1039
- Status last verified
- Aug 2025
- First submitted
- 3 Jan 2020
- Last updated
- 7 Aug 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data that underline the results reported in the article , after de-identification
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Atorvastatin ± Aspirin on Colorectal Biomarkers in Patients With Lynch Syndrome: a Pilot Study
- ClinicalTrials.gov ID
- NCT04379999
- Acronym / sponsor ID
- 18-1039
- Conditions
- Lynch Syndrome
- Keywords
- HNPCC, MLH1, MSH2, MSH6, PMS2, EPCAM, LYNCH
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 43 participants (actual)
- Lead sponsor
- Fox Chase Cancer CenterUniversity, hospital or other
- Collaborators
- Prevent Cancer Foundation
- Study start
- 10 Sep 2018 (actual)
- Primary completion
- 4 Aug 2025 (actual)
- Study completion
- 4 Aug 2025 (actual)
- First posted
- 8 May 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- One group receives atorvastatin 20 mg, and the other group receives atorvastatin 20 mg+ aspirin 325mg
| Arm | Type | Receives |
|---|---|---|
| Atorvastatin | Active comparator | Drug: Atorvastatin 20mgAtorvastatin (LIPITOR) 20 milligram tablet daily for 6 weeks |
| Atorvastatin and Aspirin | Active comparator | Drug: Atorvastatin 20mg AND Aspirin 325 mgAtorvastatin (LIPITOR) 20 milligram tablet and Aspirin 325 mg tablet daily for 6 weeks |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Atorvastatin 20mgAlso: Lipitor 20mgNo history of colorectal cancer and no colorectal adenomas within 5 years. | Drug | Atorvastatin |
| Atorvastatin 20mg AND Aspirin 325 mgAlso: Lipitor 20mg AND Aspirin 325mgHistory of colorectal cancer and/or history of colorectal adenomas within 5 years. | Drug | Atorvastatin and Aspirin |
Primary outcome
Proliferation (Ki-67) and apoptosis (active caspase 3) by immunohistochemical staining
Time frame: Changes from baseline to 6 weeks
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.
Genome-wide expression analyses using RNA-Seq
Time frame: Changes from baseline to 6 weeks
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.
3 secondary outcomes
Rate of adherence of healthy patients with Lynch Syndrome to a 6-week of the treatment regimen (atorvastatin ± aspirin).
Time frame: 6 weeks
Frequency of adverse events among patients administered atorvastatin ± aspirin for 6 weeks
Time frame: 6 weeks
Acceptability of the pilot study intervention and the willingness of the subject to participate in a similar larger study.
Time frame: 6 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2025.
- Individual participant dataSharing planned: Yes. Individual participant data that underline the results reported in the article , after de-identification
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael J Hall, MD, MS principal investigator
Fox Chase Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Atorvastatin 20mg and Atorvastatin 20mg AND Aspirin 325 mg in people with Lynch Syndrome, run by Fox Chase Cancer Center at 1 site 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 4 inclusion and 5 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: finished, as of the sponsor's last update on 7 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Proliferation (Ki-67) and apoptosis (active caspase 3) by immunohistochemical staining (time frame: Changes from baseline to 6 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 7 Aug 2025.