Omeprazole + Aspirin for Colorectal Cancer
Palo Alto (17 mi)Overseen byZora Djuric
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase < 1
Recruiting
Sponsor: University of Michigan Rogel Cancer Center
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.
What safety data exists for the combination of Omeprazole and Aspirin in treating colorectal cancer?The safety data for the combination of Omeprazole and Aspirin, particularly in the context of colorectal cancer, is not directly addressed in the provided research. However, related studies indicate that Omeprazole, a proton pump inhibitor, has been shown to reduce gastrointestinal risks associated with Aspirin use, such as ulcers and bleeding. For instance, the PA32540 trial demonstrated that combining Omeprazole with Aspirin significantly reduced the development of gastric ulcers compared to Aspirin alone. Additionally, Omeprazole has shown potential anti-carcinogenic properties in colon cancer models, suggesting a possible chemopreventive role. While these findings are promising, specific safety data for the combination in colorectal cancer treatment would require further clinical trials.14568
Is the drug Aspirin, Omeprazole promising for colorectal cancer?Yes, Aspirin and Omeprazole show promise for colorectal cancer. Aspirin is known to reduce the risk of colorectal cancer and may lower mortality after surgery. Omeprazole, typically used for acid reflux, has been shown in studies to prevent the progression of early cancerous lesions in the colon, making it a potential option for cancer prevention.2691011
What data supports the idea that Omeprazole + Aspirin for Colorectal Cancer is an effective drug?The available research shows that aspirin, when used with standard care, can improve survival rates for patients with colorectal cancer. Aspirin is noted as the best option for reducing the risk of colorectal cancer, despite some weak evidence on decreasing mortality. It is also associated with a reduced risk of developing colorectal cancer. Combining aspirin with a proton-pump inhibitor like omeprazole is being investigated to reduce side effects like peptic ulcers, making it a potentially effective combination for treatment.237912
Do I have to stop taking my current medications for the trial?Yes, you may need to stop some medications. You must avoid non-steroidal anti-inflammatory drugs (NSAIDs) and proton pump inhibitors not provided by the study for 30 days before starting and during the trial. If you're taking medications that interact with omeprazole or increase bleeding risk, you may need to stop those as well. The protocol specifies a 30-day washout period for certain medications.
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 had 5 or more polyps found in my last colonoscopy.
I have had 5 or more sessile serrated polyps found in my last colonoscopy.
I am between 18 and 75 years old.
I have a history of a specific type of colon polyps known as serrated polyps.
Exclusion Criteria
I have had stomach issues with bleeding from aspirin or NSAIDs before.
I am currently on medication that increases my risk of bleeding.
I am not taking any medications that interact with omeprazole.
I have a bleeding disorder such as hemophilia or Von Willebrand disease.
I have genetic mutations linked to colon cancer risk.
I do not have any serious illnesses or social situations that would stop me from following the study's requirements.
Treatment Details
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.
1Treatment groups
Experimental Treatment
Group I: InterventionExperimental Treatment2 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
Find a clinic near you
Research locations nearbySelect from list below to view details:
The University of Michigan Rogel Cancer CenterAnn Arbor, MI
Ohio State University Comprehensive Cancer CenterColumbus, OH
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Who is running the clinical trial?
University of Michigan Rogel Cancer CenterLead Sponsor
National Cancer Institute (NCI)Collaborator
References
Critical effect of Helicobacter pylori infection on the effectiveness of omeprazole for prevention of gastric or duodenal ulcers among chronic NSAID users. [2019]The recently reported OMNIUM and ASTRONAUT NSAID ulcer prevention trials using omeprazole to prevent endoscopic ulcer recurrence among chronic NSAID users suggested superiority over misoprostol or ranitidine.
Cyclooxygenase-2 inhibitors in colorectal cancer prevention: counterpoint. [2021]Aspirin is the best chemoprevention agent for colorectal cancer risk reduction despite the fact that the evidence for a decrease in mortality is weak. The cyclooxygenase-2 selective agents (COXIBS) have an efficacy similar to that of aspirin for most gastrointestinal (GI) lesions but not esophagus. Specifically, there are beneficial short term effects of COXIBs on the risk of colorectal adenoma as shown in the Approve, PreSAP, and APC studies. However, there is still an increased risk of upper GI complications with COXIBs when compared with placebo, and this risk may increase further in some people when aspirin is also consumed. Whereas aspirin reduces the risk of cardiovascular events, COXIBs and most traditional nonsteroidal anti-inflammatory drugs (but not all) are both associated with an increased risk of thrombotic cardiovascular events compared with placebo. In conclusion, COXIBs have a niche role for patients with familial adenomatous polyposis. The value of aspirin remains with respect for efficacy, mainly in the esophagus, and the side effect profile, especially in the elderly if given with acid suppression therapy. COXIBs should be used in younger populations, but if they are considered in the elderly because of increased GI risks, and the cardiovascular risk is also increased, then combination treatment with aspirin and a proton-pump inhibitor should also be considered instead, such as in the ASPECT trial.
Aspirin and non-steroidal anti-inflammatory drugs for cancer prevention: an international consensus statement. [2022]Evidence clearly shows a chemopreventive effect for aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) on colorectal cancer and probably other cancer types; however, data on the risk-benefit profile for cancer prevention are insufficient and no definitive recommendations can be made. Aspirin has emerged as the most likely NSAID for use in chemoprevention because of its known cardiovascular benefit and available safety and efficacy data. Other traditional NSAIDs, particularly sulindac, and selective COX-2 inhibitors are now given to patients at high risk of colorectal cancer, although these drugs do not provide cardioprotection. More studies of aspirin and cancer prevention are needed to define the lowest effective dose, the age at which to initiate therapy, the optimum treatment duration, and the subpopulations for which the benefits of chemoprevention outweigh the risks of adverse side-effects. Although it might be possible to answer some of these questions with longer follow-up of existing clinical trials, randomised controlled trials with new study designs will be needed. Future projects should investigate the effects of aspirin treatment on multiple organ systems. Cancers of interest are colorectal, breast, prostate, lung, stomach, and oesophageal. The main side-effect of aspirin is peptic ulcers; therefore coadministration of aspirin with a proton-pump inhibitor is an attractive option and is under investigation in the AspECT trial.
Novel application of proton pump inhibitor for the prevention of colitis-induced colorectal carcinogenesis beyond acid suppression. [2013]Colitis-associated cancers arise in the setting of chronic inflammation wherein an "inflammation-dysplasia-carcinoma" sequence prevails. Based on our previous findings in which the proton pump inhibitor could impose significant levels of anti-inflammatory, antiangiogenic, and selective apoptosis induction beyond gastric acid suppression, we investigated whether omeprazole could prevent the development of colitis-associated cancer in a mouse model induced by repeated bouts of colitis. Omeprazole, 10 mg/kg, was given i.p. all through the experimental periods for colitis-associated carcinogenesis. Molecular changes regarding inflammation and carcinogenesis were compared between control groups and colitis-associated cancer groups treated with omeprazole in addition to chemopreventive outcome. Nine of 12 (75.0%) mice in the control group developed multiple colorectal tumors, whereas tumors were noted in only 3 of 12 (25.0%) mice treated with daily injections of omeprazole. The cancer-preventive results of omeprazole treatment was based on significant decreases in the levels of nitric oxide, thiobarbituric acid-reactive substance, and interleukin-6 accompanied with attenuated expressions of tumor necrosis factor-alpha, inducible nitric oxide synthase, and cyclooxygenase-2. The expressions of matrix metalloproteinase (MMP)-9, MMP-11, and MT1-MMMP were significantly decreased in mice treated with omeprazole in accordance with significant decreases in the number of beta-catenin-accumulated crypts. A significant induction of apoptosis was observed in tumor tissue treated with omeprazole. Omeprazole could block the trophic effect of gastrin in colon epithelial cells. The significant anti-inflammatory, antioxidative, and antimutagenic activities of omeprazole played a cancer-preventive role against colitis-induced carcinogenesis, and our novel in vivo evidence is suggestive of chemopreventive action independent of gastric acid suppression.
Reducing the risk of gastroduodenal ulcers with a fixed combination of esomeprazole and low-dose acetyl salicylic acid. [2013]Low-dose acetyl salicylic acid (ASA) for preventing cardiovascular and cerebrovascular events is now one of the most frequently prescribed medications in some Western countries. However, it is associated with significant morbidity and mortality as a consequence of the development of gastric and duodenal ulcers and their complications. Recent randomized controlled trials in patients who are at moderately increased risk of ulcers have shown that the proton pump inhibitor esomeprazole (the S-isomer of racemic omeprazole) reduces the gastroduodenal ulcer incidence by approximately 70-85% and the gastrointestinal bleeding risk by as much as 90%. Case-control studies also indicate that the risk of ulcer bleeding is less in low-dose ASA users who concomitantly take a proton pump inhibitor. This article reviews the pharmacology of the component agents and the evidence for efficacy of the combination of esomeprazole and low-dose ASA.
Anti-carcinogenic properties of omeprazole against human colon cancer cells and azoxymethane-induced colonic aberrant crypt foci formation in rats. [2013]Omeprazole is a proton pump inhibitor, a widely used drug to treat ulcers and gastroesophageal refluxdisease. We have evaluated colon cancer chemopreventive properties of omeprazole using azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) in male F344 rats and analyzed cell growth inhibition and apoptosis induction in human colon cancer cells. Five-week-old male F344 rats were fed a control or experimental diet containing two doses of omeprazole (200 and 400 ppm). After one week, all animals were s.c. injected with AOM (15 mg/kg body weight, once weekly for two weeks). Rats continued on experimental diets for seven more weeks before being sacrificed. Colons were histopathologically evaluated for ACF. Human colon cancer HCT-116 and HCA-7 cells treated with omeprazole were evaluated for different markers associated with proliferation and apoptotic markers using Western blot technique. Rats fed with 200 and 400 ppm of omeprazole significantly suppressed total colonic ACF formation (~30%, P
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]Aspirin is associated with a reduced risk of developing colorectal cancer. This study examined whether patients with colorectal cancer prescribed aspirin had improved survival.
Aspirin Use in Secondary Cardiovascular Protection and the Development of Aspirin-Associated Erosions and Ulcers. [2017]Aspirin for secondary cardiovascular disease prevention is well established, but treatment discontinuation, often because of gastrointestinal mucosal injury or symptoms, can lead to increased risk for cardiovascular events. Proton pump inhibitor therapy is recommended for aspirin-treated patients at gastrointestinal risk. PA32540 [enteric-coated aspirin (EC-ASA) 325 mg + immediate-release omeprazole 40 mg] was compared with EC-ASA 325 mg alone once daily for 6 months in 2 duplicate, randomized double-blind trials in gastrointestinal-risk patients taking aspirin for ≥3 months for secondary prevention. In this post hoc analysis, we determined the prevalence of endoscopic upper gastrointestinal ulcers at screening and whether baseline endoscopic gastric erosions impacted subsequent ulcer development. At the screening endoscopy, 6% of subjects had upper gastrointestinal ulcers (not eligible for randomization) and 40% had gastric erosions. Conditional logistic regression modeling showed that baseline gastric erosions are significantly associated with endoscopic gastric ulcer development (OR = 2.12, 95% confidence interval, 1.26-3.57). In subjects with baseline gastric erosion, 4.2% of PA32540-treated versus 13.0% of EC-ASA-treated subjects (P = 0.001) subsequently developed endoscopic gastric ulcers. These data suggest that gastric injury predisposes to gastric ulcer development when taking EC-ASA, and exposure to immediate-release omeprazole in the presence of aspirin therapy significantly reduces the likelihood of progressing to gastric ulcers.
Effect of aspirin on the diagnostic accuracy of the faecal immunochemical test for colorectal advanced neoplasia. [2022]Aspirin (ASA) is a drug that can cause gastrointestinal lesions and symptoms. Colorectal cancer (CRC) is the most prevalent type of cancer in Western countries. We assessed the effect of aspirin on the diagnostic accuracy of the faecal immunochemical test (FIT) for CRC and/or advanced neoplasia (AN) in patients undergoing colonoscopy for gastrointestinal symptoms.
Low-dose aspirin can reduce colorectal cancer mortality after surgery: A 10-year follow-up of 13 528 colorectal cancer patients. [2019]The chemopreventive effect of aspirin in colorectal cancer (CRC) is well studied, but its benefit in patients after CRC diagnosis and surgery is unclear. This study aims to investigate the effects of low-dose aspirin use in mortality among CRC patients after surgery.
Proton Pump Inhibitor Omeprazole Suppresses Carcinogen-induced Colonic Adenoma Progression to Adenocarcinoma in F344 Rat. [2022]Colorectal cancer causes over 53,000 deaths annually in the United States. Its rising incidences worldwide and particularly in young adults is a major concern. Here, we evaluated the efficacy of omeprazole that is clinically approved for treating acid reflux, to enable its repurposing for colorectal cancer prevention. In the azoxymethane-induced rat colorectal cancer model, dietary omeprazole (250 and 500 ppm) was administered at early adenoma stage (8 weeks after azoxymethane) to assess the progression of early lesions to adenocarcinoma. Administration of omeprazole at 250 or 500 ppm doses led to suppression of total colon adenocarcinoma incidence by 15.7% and 32% (P < 0.01), respectively. Importantly, invasive carcinoma incidence was reduced by 59% (P < 0.0005) and 90% (P < 0.0001) in omeprazole-administered rats in a dose-dependent manner. There was also a strong and dose-dependent inhibition in the adenocarcinoma multiplicity in rats exposed to omeprazole. Administration of 250 and 500 ppm omeprazole inhibited total colon adenocarcinoma multiplicity by approximately 49% and approximately 65% (P < 0.0001), respectively. While noninvasive adenocarcinomas multiplicity was suppressed by approximately 34% to approximately 48% (P < 0.02), the invasive carcinomas multiplicity was reduced by approximately 74% to approximately 94% (P < 0.0001) in omeprazole-exposed rats in comparison with the untreated rats. Biomarker analysis results showed a decrease in cell proliferation and anti-apoptotic/pro-survival proteins with an increase in apoptosis. Transcriptome analysis of treated tumors revealed a significant increase in adenocarcinoma inhibitory genes (Olmf4; Spink4) expression and downregulation of progression promoting genes (SerpinA1, MMP21, IL6). In summary, omeprazole showed significant protection against the progression of adenoma to adenocarcinoma. PREVENTION RELEVANCE: Preventing colon cancer is urgently needed because of its high incidence and mortality rates worldwide. Toward this end, preventive efficacy of omeprazole, a common medication, was evaluated in animal model of colorectal cancer and was found to suppress colonic adenoma progression to carcinoma. These findings warrant its further evaluation in humans.
Meta-analysis of aspirin-guided therapy of colorectal cancer. [2022]Purpose colorectal cancer (CRC) is one of the most commonly diagnosed cancers worldwide. Some evidence has shown that aspirin can reduce the morbidity and mortality of CRC. The aim of this meta-analysis was to compare standard care of patients with CRC and standard care with the addition of aspirin in terms of the survival benefit.