Omega 3 Fatty Acids in Preventing Colorectal Cancer in Patients with Lynch Syndrome
- Ability of participant OR legally authorized representative (LAR) to understand this study, and participant or LAR willingness to sign a written informed consent.
- Candidate for elective endoscopy procedure.
- Participants with known Lynch syndrome with germline mutation in one of the deoxyribonucleic acid (DNA) mismatch repair (MMR) genes (MLH1, MSH2, MSH6, PMS2) or loss of expression of MSH2 due to deletion in the EPCAM genes.
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
- Willing to undergo a colonoscopy and biopsy at baseline and another colonoscopy and biopsy at 12 months visit.
- Participants taking aspirin for chemoprevention must agree to stop it for at least 4 weeks prior to study entry and throughout the trial period.
- Leukocytes >= 3 K / UL.
- Absolute neutrophil count >= 1.5 K / UL.
- Platelets >= 100 K / UL.
- Total bilirubin =< 1.5 X institutional upper limit of normal.
- Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT]) =< 2.5 X institutional upper limit of normal.
- Alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal.
- Creatinine: Measured creatinine clearance (CL) > 40 mL/min.
- Women of child-bearing potential and men with partners of child-bearing potential must agree to practice sexual abstinence, or to use two forms of adequate contraception (hormonal AND barrier method of birth control) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. If a woman becomes pregnant or suspects she is pregnant while participating in this study, she should inform her treating physician immediately.
- Men of child-bearing potential must not father a child or donate sperm while on this study and for 90 days after their last study treatment.
- Current or anticipated use of other investigational agents while participating in this study.
- Psychiatric illness/social situations that could limit compliance with study requirements.
- Pregnant or breast feeding. There is a potential for congenital abnormalities and for this regimen to harm breast feeding infants.
- Familial adenomatous polyposis, Putz-Jeghers disease, ulcerative colitis, or Crohn’s disease.
- Previous or known active malignancies, except non-melanoma skin cancers, unless curatively treated and with no evidence of recurrence for > 5 years, with the exception of prior microsatellite instable (MSI) high stage 1-3 colorectal cancer (CRC) which has been treated with no evidence of recurrence and with last chemotherapy > 6 months before study enrollment/registration.
- Current use of anticoagulation therapy.
- Current use of therapeutic doses of aspirin for reasons other than chemoprevention.
- Use of omega 3 fatty acids or flaxseed supplements within 4 weeks before this study’s screening/baseline colonoscopy.
- Use of high dose omega 3 fatty acids within the past 3 months prior to study baseline/screening.
- Current, regular use of non-steroidal anti-inflammatory drugs (NSAIDS) (> 7 tablets weekly).
- Allergy to fish and/or fish products.
- Uncontrolled infectious disease.
- Malabsorption syndrome, disease affecting gastrointestinal function, or previous resection of the stomach or small bowel.
- Unable to swallow and retain oral medication.
I. To determine the feasibility of an intervention with 2 grams orally per day of omega-3-acid ethyl esters (generic Lovaza) administered for 12 months to participants with Lynch syndrome.
I. To assess safety and tolerability of 2 grams orally per day omega-3-acid ethyl esters (generic Lovaza), administered for 12 months to participants with Lynch syndrome.
I. To determine the effect of 2 grams orally per day omega-3-acid ethyl esters (generic Lovaza) on colon mucosal tissue proliferation. (colon specimens will be subjected to immunohistochemistry [IHC] for markers of proliferation and apoptosis (Ki-67 and Caspase-3)
II. To assess the effect of 2 grams orally per day omega-3-acid ethyl esters (generic Lovaza) on PGE-2 levels, COX-2 & β-Catenin and EPA:AA ratios in urine, colon tissue, and blood.
III. To assess the impact of 2 grams orally per day omega-3-acid ethyl esters (generic Lovaza) on gene expression related to proliferation, apoptosis, and cell survival in colon tissue: NF-kB and Wnt pathways.
IV. To assess the impact of 2 grams orally per day omega-3-acid ethyl esters (generic Lovaza) on intestinal microbiota.
Patients receive omega-3-acid ethyl esters orally (PO) once daily (QD) on days 1-28. Cycles repeat every 28 days for 12 months in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 and 90 days.
Trial Phase Phase I
Trial Type Prevention
University of Kansas Cancer Center
- Primary ID IIT-2018-Omega3-CRC-Prev
- Secondary IDs NCI-2019-04003
- Clinicaltrials.gov ID NCT03831698