Back to resultsAtorvastatin ± Aspirin in Lynch Syndrome Syndrome
Primary Purpose
Lynch Syndrome
Status
Recruiting
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Atorvastatin 20mg
Atorvastatin 20mg AND Aspirin 325 mg
Sponsored by
About this trial
This is an interventional prevention trial for Lynch Syndrome focused on measuring HNPCC, MLH1, MSH2, MSH6, PMS2, EPCAM, LYNCH
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
Sites / Locations
- Fox Chase Cancer CenterRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
Atorvastatin
Atorvastatin and Aspirin
Arm Description
Atorvastatin (LIPITOR) 20 milligram tablet daily for 6 weeks
Atorvastatin (LIPITOR) 20 milligram tablet and Aspirin 325 mg tablet daily for 6 weeks
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
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.
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)
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04379999
Brief Title
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
2. Study Status
Record Verification Date
April 2022
Overall Recruitment Status
Recruiting
Study Start Date
September 10, 2018 (Actual)
Primary Completion Date
September 1, 2022 (Anticipated)
Study Completion Date
September 10, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fox Chase Cancer Center
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lynch Syndrome
Keywords
HNPCC, MLH1, MSH2, MSH6, PMS2, EPCAM, LYNCH
7. Study Design
Primary Purpose
Prevention
Study Phase
Early Phase 1
Interventional Study Model
Parallel Assignment
Model Description
One group receives atorvastatin 20 mg, and the other group receives atorvastatin 20 mg+ aspirin 325mg
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
46 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Atorvastatin
Arm Type
Active Comparator
Arm Description
Atorvastatin (LIPITOR) 20 milligram tablet daily for 6 weeks
Arm Title
Atorvastatin and Aspirin
Arm Type
Active Comparator
Arm Description
Atorvastatin (LIPITOR) 20 milligram tablet and Aspirin 325 mg tablet daily for 6 weeks
Intervention Type
Drug
Intervention Name(s)
Atorvastatin 20mg
Other Intervention Name(s)
Lipitor 20mg
Intervention Description
No history of colorectal cancer and no colorectal adenomas within 5 years.
Intervention Type
Drug
Intervention Name(s)
Atorvastatin 20mg AND Aspirin 325 mg
Other Intervention Name(s)
Lipitor 20mg AND Aspirin 325mg
Intervention Description
History of colorectal cancer and/or history of colorectal adenomas within 5 years.
Primary Outcome Measure Information:
Title
Proliferation (Ki-67) and apoptosis (active caspase 3) by immunohistochemical staining
Description
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.
Time Frame
Changes from baseline to 6 weeks
Title
Genome-wide expression analyses using RNA-Seq
Description
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.
Time Frame
Changes from baseline to 6 weeks
Secondary Outcome Measure Information:
Title
Rate of adherence of healthy patients with Lynch Syndrome to a 6-week of the treatment regimen (atorvastatin ± aspirin).
Description
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.
Time Frame
6 weeks
Title
Frequency of adverse events among patients administered atorvastatin ± aspirin for 6 weeks
Description
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)
Time Frame
6 weeks
Title
Acceptability of the pilot study intervention and the willingness of the subject to participate in a similar larger study.
Description
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.
Time Frame
6 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yana Chertock, MA
Phone
215-214-3216
Email
yana.chertock@fccc.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael J Hall, MD, MS
Organizational Affiliation
Fox Chase Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fox Chase Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19111
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yana Chertock, MA
Phone
215-214-3216
Email
yana.chertock@fccc.edu
First Name & Middle Initial & Last Name & Degree
Michael Hall, MD, MS
Phone
215-728-2791
Email
michael.hall@fccc.edu
First Name & Middle Initial & Last Name & Degree
Michael J Hall, MD, MS
First Name & Middle Initial & Last Name & Degree
Margie L Clapper, PhD
First Name & Middle Initial & Last Name & Degree
Minhhuyen T Nguyen, MD,AGAF,FACP
First Name & Middle Initial & Last Name & Degree
Harry S Cooper, MD
First Name & Middle Initial & Last Name & Degree
Wen-Chi L Chang, PhD
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Individual participant data that underline the results reported in the article , after de-identification
IPD Sharing Time Frame
beginning 9 months and ending 3 years following article publication
IPD Sharing 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.
Learn more about this trial
Atorvastatin ± Aspirin in Lynch Syndrome Syndrome
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