Omeprazole + Aspirin for Colorectal Cancer

Recruiting at 1 trial location

Overseen By Kirsten Tuck

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Michigan Rogel Cancer Center

Must be taking: Omeprazole, Aspirin

Must not be taking: NSAIDs, Anticoagulants

Disqualifiers: Age 76+, Genetic syndromes, Cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: 4-6 weeks

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether combining omeprazole and low-dose aspirin can prevent colorectal cancer by analyzing changes in colorectal tissue. Participants will take these medications daily for about a month and undergo biopsies during colonoscopy procedures to collect tissue samples. The trial suits individuals with five or more adenomas or serrated polyps, or an incompletely removed polyp in the colon or rectum. Participants should avoid certain medications and must not have conditions that increase bleeding risk. As an Early Phase 1 trial, this research aims to understand how the treatment works in people, offering participants a chance to contribute to groundbreaking research.

Will I have to stop taking my current medications?

Participants must stop taking non-steroidal anti-inflammatory drugs (NSAIDs) and proton pump inhibitors (PPIs) that are not provided by the study for 30 days before starting and during the study. If you are taking medications that interact with omeprazole or increase bleeding risk, you may need to stop those as well.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that both omeprazole and low-dose aspirin have been studied for safety in people. Omeprazole, a common medicine for reducing stomach acid, has not been linked to an increased risk of colorectal cancer in previous studies, indicating it is generally safe, though long-term effects remain under investigation.

Aspirin, particularly in low doses, is often used for heart health and has also been studied for safety. Most people tolerate it well, but it can sometimes cause stomach upset or increase the risk of bleeding. The low dose used in this trial matches what many people take daily for heart protection.

Overall, past research on these medications suggests they are well-tolerated in the amounts planned for this trial. However, as with any medication, individual experiences may vary. Participants should consult their healthcare provider about potential risks before joining any trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for colorectal cancer?

Researchers are excited about the combination of omeprazole and aspirin for colorectal cancer because it offers a potentially unique approach by combining a common anti-inflammatory drug with a proton pump inhibitor. While aspirin is known for its anti-inflammatory and anti-cancer properties, omeprazole helps reduce the risk of stomach irritation and bleeding, which are common side effects of long-term aspirin use. This combination could enhance the benefits of aspirin while minimizing its drawbacks, potentially offering a safer and more effective treatment option for colorectal cancer.

What evidence suggests that this treatment might be an effective preventive measure for colorectal cancer?

Studies have shown that aspirin can lower the risk of colorectal cancer and may help patients with this cancer live longer. This trial will administer a combination of aspirin and omeprazole to participants. Researchers are studying omeprazole, a common medicine for stomach issues, to understand its effects when combined with aspirin. They are investigating whether this combination influences changes in colon cells that could lead to cancer. While aspirin's potential to fight cancer is well-known, the role of omeprazole remains under investigation. Early results suggest a possible benefit, but further research is needed to confirm its effectiveness. ^{1 2 3 4 6}

Who Is on the Research Team?

Zora Djuric

Principal Investigator

University of Michigan Rogel Cancer Center

Are You a Good Fit for This Trial?

This trial is for people who've had at least 5 adenomas or serrated polyps, or an incompletely removed one in the colon/rectum. They must consent to daily medication and two tissue biopsies during colon exams.

Inclusion Criteria

I had colorectal polyps that were not completely removed.

I have a history of a specific type of colon polyps known as serrated polyps.

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 since endoscopy is not recommended during pregnancy

Exclusion Criteria

I am currently on medication that increases my risk of bleeding.

I have had stomach issues with bleeding from aspirin or NSAIDs before.

Pregnant women are excluded since endoscopy is not recommended while pregnant

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants take two 20 mg omeprazole tablets and two 81 mg aspirin tablets each day before the first meal for 25-45 days

4-6 weeks

2 visits (in-person) for biopsies

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Aspirin
• Omeprazole

Trial Overview The study tests if omeprazole (40 mg) and low-dose aspirin (162 mg) taken daily can prevent colorectal cancer by looking for changes in biomarkers from tissue samples before and after treatment.

How Is the Trial Designed?

Group I: Intervention Experimental Treatment 2 Interventions

Two 20 mg/day omeprazole tablets and two 81 mg/day aspirin tablets taken before the first meal each day for 25-45 days.

Aspirin is already approved in European Union, United States, Canada, China for the following indications:

Approved in European Union as Aspirin for:

• Pain relief
• Fever reduction
• Inflammation
• Cardiovascular disease prevention
• Preeclampsia prevention

Approved in United States as Aspirin for:

• Pain relief
• Fever reduction
• Inflammation
• Cardiovascular disease prevention
• Preeclampsia prevention

Approved in Canada as Aspirin for:

• Pain relief
• Fever reduction
• Inflammation
• Cardiovascular disease prevention
• Preeclampsia prevention

Approved in China as Aspirin for:

• Pain relief
• Fever reduction
• Inflammation
• Cardiovascular disease prevention

Who Is Running the Clinical Trial?

University of Michigan Rogel Cancer Center

Lead Sponsor

Trials

303

Recruited

20,700+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 3052 patients undergoing colonoscopy, aspirin use did not affect the diagnostic accuracy of the faecal immunochemical test (FIT) for detecting colorectal cancer (CRC) or advanced neoplasia (AN).

However, patients taking 300 mg/day or more of aspirin showed a lower prevalence of advanced neoplasia and had significantly reduced sensitivity and specificity in the FIT test, indicating that high doses of aspirin may impair test accuracy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of aspirin on the diagnostic accuracy of the faecal immunochemical test for colorectal advanced neoplasia. Bujanda, L., Sarasqueta, C., Vega, P., et al.[2022]

In a study of 13,528 colorectal cancer (CRC) patients, continuous low-dose aspirin use after surgery significantly reduced CRC-related mortality by 31% and all-cause mortality by 39%.

Even patients who did not use aspirin before their CRC diagnosis benefited from starting low-dose aspirin after surgery, which lowered CRC-related mortality by 12% and all-cause mortality by 13%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-dose aspirin can reduce colorectal cancer mortality after surgery: A 10-year follow-up of 13 528 colorectal cancer patients. Sung, JJY., Ho, JMW., Chan, FCH., et al.[2019]

In a rat model of colorectal cancer, dietary omeprazole significantly reduced the incidence of total colon adenocarcinoma by up to 32% and invasive carcinoma by up to 90%, indicating its potential as a preventive treatment.

Omeprazole not only inhibited the progression of adenomas to carcinomas but also altered gene expression related to cancer progression, suggesting a mechanism of action that involves reducing cell proliferation and promoting apoptosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton Pump Inhibitor Omeprazole Suppresses Carcinogen-induced Colonic Adenoma Progression to Adenocarcinoma in F344 Rat. Madka, V., Kumar, G., Pathuri, G., et al.[2022]

In a study with male F344 rats, omeprazole significantly reduced the formation of colonic aberrant crypt foci (ACF) by approximately 30%, indicating its potential as a chemopreventive agent against colon cancer.

In human colon cancer cell lines, omeprazole induced the expression of the tumor suppressor protein p21 and decreased levels of anti-apoptotic proteins, suggesting that it may inhibit cancer cell growth and promote apoptosis in a dose-dependent manner.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-carcinogenic properties of omeprazole against human colon cancer cells and azoxymethane-induced colonic aberrant crypt foci formation in rats. Patlolla, JM., Zhang, Y., Li, Q., et al.[2013]

A meta-analysis of 27 studies involving 237,245 colorectal cancer patients found that postdiagnosis aspirin use significantly improves CRC-specific survival, with a hazard ratio of 0.74, indicating a 26% reduction in cancer-related deaths.

Patients with specific genetic markers, such as the PIK3CA mutation and high expression of COX-2, showed even greater survival benefits from aspirin, suggesting that these factors may help identify which patients could benefit most from this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meta-analysis of aspirin-guided therapy of colorectal cancer. Mädge, JC., Stallmach, A., Kleebusch, L., et al.[2022]

In a study of 2,990 colorectal cancer patients, those who used aspirin after their diagnosis had a significantly lower risk of dying from any cause (hazard ratio of 0.67) and from colorectal cancer specifically, suggesting a potential survival benefit.

The findings indicate that aspirin may play a role in improving survival rates for colorectal cancer patients, but further research is needed to confirm this relationship and determine which patient groups might benefit the most.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of aspirin post-diagnosis in a cohort of patients with colorectal cancer and its association with all-cause and colorectal cancer specific mortality. McCowan, C., Munro, AJ., Donnan, PT., et al.[2022]

Omeprazole was confirmed to be superior to placebo in preventing ulcer recurrence in chronic NSAID users, but it did not show significant superiority over a low dose of misoprostol or ranitidine for gastric ulcer prevention.

In fact, misoprostol was found to be more effective than omeprazole for preventing gastric ulcers in NSAID users, especially those with an active Helicobacter pylori infection, suggesting that the effectiveness of omeprazole may be overestimated in these populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Critical effect of Helicobacter pylori infection on the effectiveness of omeprazole for prevention of gastric or duodenal ulcers among chronic NSAID users. Graham, DY.[2019]

In a study involving patients at gastrointestinal risk taking aspirin for cardiovascular disease prevention, baseline gastric erosions were found to significantly increase the risk of developing gastric ulcers, with an odds ratio of 2.12.

The combination of enteric-coated aspirin and immediate-release omeprazole (PA32540) significantly reduced the incidence of gastric ulcers compared to enteric-coated aspirin alone, with only 4.2% of patients on PA32540 developing ulcers compared to 13.0% on aspirin alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aspirin Use in Secondary Cardiovascular Protection and the Development of Aspirin-Associated Erosions and Ulcers. Goldstein, JL., Scheiman, JM., Fort, JG., et al.[2017]

In a mouse model of colitis-associated cancer, treatment with omeprazole significantly reduced the incidence of colorectal tumors, with only 25% of treated mice developing tumors compared to 75% in the control group.

Omeprazole demonstrated cancer-preventive effects through anti-inflammatory and antioxidative mechanisms, including decreased levels of inflammatory markers and increased apoptosis in tumor tissues, suggesting its potential as a chemopreventive agent independent of its role in gastric acid suppression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel application of proton pump inhibitor for the prevention of colitis-induced colorectal carcinogenesis beyond acid suppression. Kim, YJ., Lee, JS., Hong, KS., et al.[2013]

Aspirin is the most effective agent for reducing colorectal cancer risk, although evidence for its impact on mortality is limited, while COXIBs show similar efficacy for gastrointestinal lesions but carry a higher risk of upper GI complications.

COXIBs may be beneficial for patients with familial adenomatous polyposis, but their use in older adults should be cautious due to increased GI and cardiovascular risks, suggesting that combining them with aspirin and proton-pump inhibitors may be safer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cyclooxygenase-2 inhibitors in colorectal cancer prevention: counterpoint. Jankowski, J., Hunt, R.[2021]

Aspirin and other NSAIDs show promise in preventing colorectal cancer and potentially other cancers, but more research is needed to fully understand their risk-benefit profiles and to make definitive recommendations.

Aspirin is favored for chemoprevention due to its cardiovascular benefits, but studies are required to determine the optimal dosage, treatment duration, and specific populations that would benefit most while minimizing side effects like peptic ulcers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aspirin and non-steroidal anti-inflammatory drugs for cancer prevention: an international consensus statement. Cuzick, J., Otto, F., Baron, JA., et al.[2022]

Low-dose acetyl salicylic acid (ASA) is commonly prescribed for preventing cardiovascular and cerebrovascular events, but it can lead to serious complications like gastric and duodenal ulcers.

The proton pump inhibitor esomeprazole significantly reduces the incidence of these ulcers by 70-85% and the risk of gastrointestinal bleeding by up to 90%, making it a beneficial co-treatment for patients using low-dose ASA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reducing the risk of gastroduodenal ulcers with a fixed combination of esomeprazole and low-dose acetyl salicylic acid. Yeomans, ND.[2013]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8641055/

Proton pump inhibitors and colorectal cancer: A systematic ... Treatment studies suggest that concomitant use of PPI with capecitabine use may reduce the efficacy of chemotherapy and result in poorer oncological outcomes.

2. cancer.gov cancer.gov/clinicaltrials/NCI-2023-06348

Omeprazole and Low Dose Aspirin to Identify Colorectal ... The information gained from this study could help researchers determine if giving omeprazole and low dose aspirin affects abnormal changes in colorectal cells ...

3. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/478917

A Trial of Omeprazole and Low Dose Aspirin to Identify ... This trial will obtain biomarker data on the possible preventive effects of omeprazole and low-dose aspirin in colorectal tissue.

4. withpower.com withpower.com/trial/early-phase-1-colorectal-neoplasia-4-2024-307ba

Omeprazole + Aspirin for Colorectal Cancer Research shows that aspirin can reduce the risk of developing colorectal cancer and may improve survival in patients with this cancer. Combining aspirin with a ...

5. nature.com nature.com/articles/s41598-025-05570-4

Proton pump inhibitors and all-cause mortality in colorectal ... The study indicates that PPIs are associated with increased all-cause mortality in CRC. This highlights the need for careful consideration when prescribing ...

6. gut.bmj.com gut.bmj.com/content/71/1/111

Proton pump inhibitors and risk of colorectal cancer - Gut While the use of PPIs was not associated with an overall increased risk of colorectal cancer (HR: 1.02, 95% CI 0.92 to 1.14), HRs increased with cumulative ...