Omeprazole + Aspirin for Colorectal Cancer

Recruiting at1 trial location

Overseen by Zora Djuric

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase < 1

Recruiting

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

Trial Summary

What is the purpose of this trial?

This trial will obtain biomarker data on the possible preventive effects of omeprazole and low-dose aspirin in colorectal tissue. Persons who have had 5 or more adenomas, 5 or more serrated polyps, or an incompletely removed adenoma or serrated polyp in the colon or rectum are potentially eligible. Before participating in the study, study staff will explain the study and review the consent form. If you are interested and provide consent, study staff will then confirm your eligibility. Once enrolled, participants will take two 20 mg omeprazole tablets and two 81 mg aspirin tablets each day before the first meal each day for 25-45 days. The study does involve biopsies of the colorectal tissue before and after taking the study medications. The biopsies are samples of tissue, about the size of a grain of rice, that will be taken from the colon or rectum before and after taking the study medications. This is done during a usual, clinical colonoscopy exam and during one more limited exam, called flexible sigmoidoscopy, that is done for the research study. The flexible sigmoidoscopy requires less preparation. Which procedure comes first depends on what fits best with each participant's clinical scenario. Biopsies of both normal mucosa and polyps (if possible) are collected.

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.

What data supports the effectiveness of the drug 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 proton-pump inhibitor like omeprazole is being studied to reduce side effects and enhance benefits. ^{1 2 3 4 5}

Is the combination of omeprazole and aspirin safe for humans?

The combination of omeprazole and aspirin has been studied for safety, particularly in reducing the risk of stomach ulcers when aspirin is used for heart disease prevention. Omeprazole, a drug that reduces stomach acid, can help protect the stomach lining from damage caused by aspirin, which is known to cause stomach issues like ulcers. ^{6 7 8 9 10}

How does the drug combination of Omeprazole and Aspirin work for colorectal cancer?

The combination of Omeprazole and Aspirin for colorectal cancer is unique because Omeprazole, typically used for acid reflux, has shown potential in preventing the progression of early colon lesions to cancer, while Aspirin is known for its cancer risk reduction properties. This combination may offer a novel approach by leveraging Omeprazole's ability to suppress cancer progression and Aspirin's chemopreventive effects. ^{1 3 7 11 12}

Research Team

Zora Djuric

Principal Investigator

University of Michigan Rogel Cancer Center

Eligibility Criteria

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

Trial Timeline

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

Treatment Details

Interventions

• Aspirin (Antiplatelet Agent)
• Omeprazole (Proton Pump Inhibitor)

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.

Participant Groups

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 Canada, China for the following indications:

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+

Marschall S. Runge

University of Michigan Rogel Cancer Center

Chief Executive Officer since 2015

MD, PhD

Eric R. Fearon

University of Michigan Rogel Cancer Center

Chief Medical Officer since 2016

MD, PhD

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Findings from Research

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]

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]

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]

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 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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Effect of aspirin on the diagnostic accuracy of the faecal immunochemical test for colorectal advanced neoplasia. [2022]

2. Germany pubmed.ncbi.nlm.nih.gov

Meta-analysis of aspirin-guided therapy of colorectal cancer. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Cyclooxygenase-2 inhibitors in colorectal cancer prevention: counterpoint. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Aspirin and non-steroidal anti-inflammatory drugs for cancer prevention: an international consensus statement. [2022]

5. England 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. [2022]

6. England 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. [2019]

7. Greece 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. [2013]

8. United States pubmed.ncbi.nlm.nih.gov

Aspirin Use in Secondary Cardiovascular Protection and the Development of Aspirin-Associated Erosions and Ulcers. [2017]

9. United States pubmed.ncbi.nlm.nih.gov

Novel application of proton pump inhibitor for the prevention of colitis-induced colorectal carcinogenesis beyond acid suppression. [2013]

10. England pubmed.ncbi.nlm.nih.gov

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

11. Australia 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. [2019]

12. United States pubmed.ncbi.nlm.nih.gov

Proton Pump Inhibitor Omeprazole Suppresses Carcinogen-induced Colonic Adenoma Progression to Adenocarcinoma in F344 Rat. [2022]