Clinical trial NCT04379999: Atorvastatin ± Aspirin in Lynch Syndrome Syndrome
Official title: Impact of Atorvastatin ± Aspirin on Colorectal Biomarkers in Patients With Lynch Syndrome: a Pilot Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Lynch Syndrome
Keywords: HNPCC
MLH1
MSH2
MSH6
PMS2
EPCAM
LYNCH
Lead sponsor: Fox Chase Cancer Center
Sponsor class: OTHER
First posted: 2020-05-08
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: One group receives atorvastatin 20 mg, and the other group receives atorvastatin 20 mg+ aspirin 325mg
Primary purpose: PREVENTION

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Proliferation (Ki-67) and apoptosis (active caspase 3) by immunohistochemical staining
timeFrame: Changes from baseline to 6 weeks
measure: Genome-wide expression analyses using RNA-Seq
timeFrame: Changes from baseline to 6 weeks
Secondary outcomes:
measure: Rate of adherence of healthy patients with Lynch Syndrome to a 6-week of the treatment regimen (atorvastatin ± aspirin).
timeFrame: 6 weeks
measure: Frequency of adverse events among patients administered atorvastatin ± aspirin for 6 weeks
timeFrame: 6 weeks
measure: Acceptability of the pilot study intervention and the willingness of the subject to participate in a similar larger study.
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
Study officials:
affiliation: Fox Chase Cancer Center
name: Michael J Hall, MD, MS
role: PRINCIPAL_INVESTIGATOR
References: