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

NCT05411718 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: 2022-0117NCI-2022-047941R01CA257375-01
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

T Cells; Colorectal Cancer; Lynch Syndrome

Outcome Measures

Primary Outcomes (1)

• To establish the effect of naproxen or aspirin on the abundance of T cells and other immune

  through study completion, an average of 1 year

Study Arms (2)

Naproxen

EXPERIMENTAL

Participants will take two (2) naproxen matching capsules by mouth 1 time every day, at about the same time each day

Drug: Naproxen

Aspirin

ACTIVE COMPARATOR

Participants will take two (2) aspirin matching capsules by mouth 1 time every day, at about the same time each day

Drug: Aspirin

Interventions

Naproxen DRUG

Given by PO

Naproxen

Aspirin DRUG

Given by PO

Aspirin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have Lynch syndrome defined as meeting any of the following:
• "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).
• "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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Institutes of Health (NIH): collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Colorectal Neoplasms; Colorectal Neoplasms, Hereditary Nonpolyposis

Interventions

Naproxen; Aspirin

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplastic Syndromes, Hereditary; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Naphthaleneacetic Acids; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives

Study Officials

• Eduardo Vilar-Sanchez, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Eduardo Vilar-Sanchez, MD

CONTACT

(713) 563-4743; evilar@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 1, 2022
• First Posted: June 9, 2022
• Study Start: March 21, 2023
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): November 30, 2026
• Last Updated: November 13, 2025

Record last verified: 2025-11

Locations

US (1)