A Phase IIa Randomized, Double-Blinded Clinical Trial of Naproxen or Aspirin for Cancer Immune Interception in Lynch Syndrome

A Phase IIa Randomized, Double-Blinded Clinical Trial of Naproxen or Aspirin for Cancer Immune Interception in Lynch Syndrome (NCT05411718) is a Phase 2 interventional studying T Cells and Colorectal Cancer, sponsored by M.D. Anderson Cancer Center. RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

About This Trial

To learn about the effects of naproxen and aspirin on the normal colon in people with Lynch Syndrome.

What Stage of Research Is This?

Phase 2 trials evaluate whether a treatment actually works against T Cells and continue monitoring side effects. Phase 2 enrolls larger groups (typically 100–300 patients) and produces the first real efficacy signal. A successful Phase 2 readout is what unlocks the much larger Phase 3 confirmatory trials needed for FDA approval.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

With a target enrollment of 40 participants, this is a small study — typical of early-phase research, rare-disease trials, or pilot studies designed to generate preliminary signal before a larger study is launched.

Who May Be Eligible (Plain English)

Who May Qualify: - Participants must have Lynch syndrome defined as meeting any of the following: 1. "Mutation-Positive Lynch syndrome": carriers or obligate carriers (by pedigree) of a pathogenic mutation in one of the DNA mismatch repair (MMR) genes (i.e., MLH1, MSH2/EPCAM, MSH6, or PMS2). 2. "Mutation-Negative Lynch syndrome": patients with a personal history of a non-sporadic MMR deficient premalignant lesion (i.e., polyp) or a non-sporadic MMR deficient malignant tumor (where "non-sporadic MMR deficient" is defined by: microsatellite-instability high by either immunohistochemistry or MSI testing or both, but no evidence of MLH1 promoter methylation in cases with loss of both MLH1 and PMS2, and/or no evidence of BRAF mutation in cases with loss of both MLH1 and PMS2) but germline MMR genetic testing showed either a variant of unknown significance or mutation negative result or had declined germline MMR genetic test-ing. - Participants must not have evidence of active/recurrent malignant disease for 6 months. - Participants must be at least 6 months from any prior cancer-directed treatment (such as surgical resection, chemotherapy, immunotherapy, hormonal therapy or radiation). - Participants must have endoscopically accessible distal colon and/or rectal mucosa (i.e., partici-pants must have at least part of the descending/sigmoid colon and/or rectum intact). - Participants must consent to one standard of care lower GI endoscopy (flexible sigmoidoscopy or colonoscopy) with biopsies and one flexible sigmoidoscopy with biopsies that will be 12 months (+14 days) apart. - Participants must consent to refrain from using aspirin or NSAIDs or COX-inhibitors for the du-ration of the trial - Age ≥18 years. Because no dosing or adverse event data are currently available on the long-term use of naproxen or aspirin in patients \<18 years of age, children are excluded from this study but will be eligible for future pediatric trials, if applicable. ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language

Inclusion Criteria: * Participants must have Lynch syndrome defined as meeting any of the following: 1. "Mutation-Positive Lynch syndrome": carriers or obligate carriers (by pedigree) of a pathogenic mutation in one of the DNA mismatch repair (MMR) genes (i.e., MLH1, MSH2/EPCAM, MSH6, or PMS2). 2. "Mutation-Negative Lynch syndrome": patients with a personal history of a non-sporadic MMR deficient premalignant lesion (i.e., polyp) or a non-sporadic MMR deficient malignant tumor (where "non-sporadic MMR deficient" is defined by: microsatellite-instability high by either immunohistochemistry or MSI testing or both, but no evidence of MLH1 promoter methylation in cases with loss of both MLH1 and PMS2, and/or no evidence of BRAF mutation in cases with loss of both MLH1 and PMS2) but germline MMR genetic testing showed either a variant of unknown significance or mutation negative result or had declined germline MMR genetic test-ing. * Participants must not have evidence of active/recurrent malignant disease for 6 months. * Participants must be at least 6 months from any prior cancer-directed treatment (such as surgical resection, chemotherapy, immunotherapy, hormonal therapy or radiation). * Participants must have endoscopically accessible distal colon and/or rectal mucosa (i.e., partici-pants must have at least part of the descending/sigmoid colon and/or rectum intact). * Participants must consent to one standard of care lower GI endoscopy (flexible sigmoidoscopy or colonoscopy) with biopsies and one flexible sigmoidoscopy with biopsies that will be 12 months (+14 days) apart. * Participants must consent to refrain from using aspirin or NSAIDs or COX-inhibitors for the du-ration of the trial * Age ≥18 years. Because no dosing or adverse event data are currently available on the long-term use of naproxen or aspirin in patients \<18 years of age, children are excluded from this study but will be eligible for future pediatric trials, if applicable. * ECOG performance status ≤1 OR Karnofsky ≥70%; see Appendix A. * Participants must have normal organ and marrow function as defined below: Hemoglobin \>10 g/dL or Hematocrit \> 30 % Leukocyte count ≥3,000/microliter Platelet count ≥100,000/microliter Absolute neutrophil count ≥1,500/microliter Creatinine ≤1.5 x institutional ULN (OR GFR \>30ml/min/1.73m2) Total bilirubin ≤2 x institutional ULN AST (SGOT) ≤2.5 × institutional ULN ALT (SGPT) ≤2.5 × institutional ULN * The effects of naproxen on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because NSAIDs are known to be teratogenic, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) for the duration of study participation. Should a woman become pregnant or suspect she is pregnant at the time of study entry or while participating in this study, she should inform her study physician immediately. Women of childbearing potential must agree to base-line and pre-drug pregnancy tests. * Ability to understand and the willingness to sign a written informed consent document. * Willing and able to adhere to the prohibitions and restrictions specified in the final approved pro-tocol. * Willing to undergo yearly standard of care screening colonoscopy for the duration of the clinical trial. Exclusion Criteria: * Individuals with presence of two somatic mutations/loss of heterozygosity (LOH) in one of the four MMR genes (MLH1, MSH2, MSH6, and PMS2) in MMR-deficient neoplasm (defined as a tumor with MSI-H by PCR analysis or loss of staining in one of the four MMR proteins). * Individuals who received scheduled NSAIDs or COX-inhibitors of any kind for \>3 days during anytime within the 2 weeks prior to baseline eligibility screening visit. By exception, individuals receiving cardio-protective aspirin (e.g., 81 mg PO daily) will be eligible provided they are will-ing to stop no less than 7 days prior to starting on naproxen or aspirin in this study. * Individuals who are status post total proctocolectomy (i.e., removal of all colon and rectum). * Individuals with active gastroduodenal ulcer disease in the preceding 5 years. * Individuals with any history of transfusion-dependent gastrointestinal bleeding, gastrointestinal perforation or gastrointestinal obstruction. If any of these events had been due to a malignancy of the GI tract and the malignancy has since been removed, the patient is eligible. * Individuals with history of myocardial infarction, stroke, coronary-artery bypass draft, invasive coronary revascularization in the preceding 5 years. * Individuals taking the drugs listed below may not be randomized unless they are willing to stop the medications (and possibly change to alternative non-excluded medications to treat the same conditions) no less than 7 days prior to starting naproxen or aspirin on this study. Consultation with the participant's primary care provider may be obtained but is not required. The use of the following drugs or drug classes is prohibited during naproxen/aspirin treatment: * Investigational agents; * NSAIDs: such as ketorolac, sulindac, ibuprofen, and others; * COX-2 inhibitors: such as Celecoxib, Rofecoxib and other COX-2; * Antiplatelet agents: such as aspirin, clopidogrel, ticlopidine, dipyridamole, abciximab, tirofi-ban, eptifibatide and prasugrel; * Anticoagulants: * Heparin; * Heparinoids: such as fondaparinux, danaparoid and other heparinoids; * Low-molecular weight heparins: such as enoxaparin, dalteparin, parnaparin, reviparin, tinzaparin, ardeparin, certoparin, lepidurin, bivalidurin; * Other anticoagulants: argatroban, apixaban, dabigatran, rivaroxaban, warfarin, aceno-coumarol, dicumarol, phenindione and other anticoagulants; * Lithium; * Selective serotonin and norepinephrine reuptake inhibitors: minalcipran, fluoxetine, paroxe-tine, nefazadine, citalopram, clovoxamine, escitalopram, flesinoxan, femoxitene, duloxetine, venlafaxine, vilazodone, sibutramine, desvenlafaxine; * Anticonvulsants: phenytoin, parakdehyde, valproic acid, carbamazepine, trimethadione, phenobarbital, diazepam, chlormethiazole, mephenytoin, ethotoin, paramethadione, phenac-emide, mephobarbital, oxcarbazepine, zonisamide, piracetam, vigabatrin, felbamate, gabapentin, beclamide, phosphenytoin, stripentol, tiagabine, topiramate, pregabalin, lacosa-mide, rufinamide, caramiphen; * Antibiotics and antifungals: o Fluorquinolones: such as ofloxacin, norfloxacin, levofloxacin; * Other agents: teriflunomide, cyclosporine, tacrolimus, ginkgo, gossypol, meadowsweet, fe-verfew, beta glucan, pentosan, pentoxifylline, cilostazol, erlotinib, pemetrexed, methotrex-ate, pralatrexate. * Individuals with uncontrolled renal insufficiency or renal failure. * History of allergic reactions attributed to naproxen or aspirin. * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, uncon-trolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, cardiac ar-rhythmia, or psychiatric illness/social situations that would limit compliance with study require-ments. * Pregnant, breast-feeding, or women of childbearing potential unwilling to use a reliable contra-ceptive method. Pregnant women are excluded from this study because Naproxen/NSAIDs is an agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with naproxen or aspirin, breastfeeding should be discontinued if the mother is treated with naproxen. Inclusion of Women and Minorities: -Participants will be adult men and women of all races and ethnic groups, who are at least 18 years old, and who are deemed eligible for this trial. Children will not be recruited to the trial. Our minority recruitment strategies will include identifying participants through the University of Texas MD Anderson Cancer Center Familial High-Risk Gastrointestinal Cancer Clinic and Weill Cornell Med-ical College. We will advertise the study on minority and other national websites.

Treatments Being Tested

DRUG

Naproxen

Given by PO

DRUG

Aspirin

Given by PO

Locations (1)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

MD Anderson Cancer Center

Houston, Texas, United States

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT05411718), the sponsor (M.D. Anderson Cancer Center), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT05411718 clinical trial studying?

To learn about the effects of naproxen and aspirin on the normal colon in people with Lynch Syndrome. The full protocol is registered on ClinicalTrials.gov and includes the primary outcome measures, eligibility criteria, and study endpoints.

Who can participate in NCT05411718?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT05411718?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

Source: ClinicalTrials.gov API v2 record for NCT05411718. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT05411718. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-05-08 · Data from ClinicalTrials.gov.