Lifestyle Changes + Aspirin + Vitamin D for Colorectal Cancer

Recruiting in Palo Alto (17 mi)

Overseen by Scott Kopetz, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: M.D. Anderson Cancer Center

Must be taking: Aspirin, Vitamin D

Must not be taking: Anticoagulants

Disqualifiers: Concurrent malignancy, Active bleeding, Pregnancy, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial is testing if healthy lifestyle changes, along with daily aspirin and vitamin D, can help prevent colorectal cancer from coming back in patients who have a small amount of cancer left after treatment. The goal is to see if these interventions can clear the remaining cancer cells and reduce the chance of it coming back. The study will measure how well these methods work over time. Aspirin has been shown in multiple studies to reduce the risk of colorectal cancer incidence, coming back, and death.

Do I need to stop my current medications to join the trial?

The trial requires that you do not use certain blood thinners like warfarin, Eliquis, or Xarelto. If you are on these medications, you would need to stop them to participate.

What data supports the effectiveness of the treatment Lifestyle Changes + Aspirin + Vitamin D for Colorectal Cancer?

Research shows that aspirin can help prevent colorectal cancer and may reduce cancer recurrence when used regularly. Additionally, lifestyle changes like increased physical activity and a healthy diet, along with vitamin D, are associated with a lower risk of colorectal cancer and improved outcomes for those already diagnosed. ^{1 2 3 4 5}

Is the combination of lifestyle changes, aspirin, and vitamin D safe for humans?

Aspirin is generally safe for humans but can cause side effects like peptic ulcers (sores in the stomach lining) and may increase the risk of bleeding, including hemorrhagic stroke (bleeding in the brain). Regular physical exercise and a healthy diet are safe and beneficial for overall health. Vitamin D is also generally safe, but high doses can lead to health issues like kidney damage. ^{3 6 7 8 9}

How does the treatment of lifestyle changes, aspirin, and vitamin D for colorectal cancer differ from other treatments?

This treatment is unique because it combines lifestyle changes with aspirin and vitamin D, which are not typically used together for colorectal cancer. Aspirin is known for its potential to reduce colorectal cancer risk, and vitamin D may have health benefits, but combining these with lifestyle changes could offer a more holistic approach to prevention and management. ^{2 4 7 10 11}

Research Team

Scott Kopetz, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for adults over 18 with high-risk stage II, III, or IV colorectal cancer who've had surgery or ablation and show no signs of disease. They must have a certain blood cell count, be able to consent and fill out questionnaires. It's not for those allergic to vitamin D or aspirin, on active treatment for another cancer, with kidney issues, pregnant/nursing women, prone to hypercalcemia or urinary stones, have GI bleeding/ulcers, are on certain blood thinners or can't exercise safely.

Inclusion Criteria

No radiographic evidence of disease by contrast enhanced CT chest/abdomen/pelvis

My blood test shows cancer DNA that matches my tumor.

I have finished all my standard cancer treatments.

Exclusion Criteria

I currently have active stomach bleeding or ulcers.

My doctor thinks it's unsafe for me to do physical activities.

I am currently taking blood thinners like warfarin, Eliquis, or Xarelto.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daily aspirin and vitamin D, along with lifestyle interventions such as diet and exercise, for up to 90 days

12 weeks

Follow-up

Participants are monitored for ctDNA dynamics and recurrence rate every 3 months after treatment, up to 12 months

9 months

Treatment Details

Interventions

• Aspirin (Nonsteroidal Anti-inflammatory Drug)
• Behavioral Support Counseling Sessions (Behavioral Intervention)
• Diet (Behavioral Intervention)
• Physical Activity (Behavioral Intervention)
• Vitamin D (Vitamin)

Trial Overview The study tests if lifestyle changes like diet and exercise along with daily aspirin and vitamin D can prevent advanced colorectal cancer from returning. Participants will also receive behavioral support counseling sessions to help maintain these lifestyle adjustments.

Participant Groups

Group I: Aspirin, Vitamin D Experimental Treatment 5 Interventions

by mouth every day for up to 90 days

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Dr. Peter WT Pisters

M.D. Anderson Cancer Center

Chief Executive Officer since 2017

MD from University of Western Ontario

Dr. Jeffrey E. Lee

M.D. Anderson Cancer Center

Chief Medical Officer

MD from Stanford University School of Medicine

Findings from Research

Non-aspirin NSAIDs were found to be the most effective agents for preventing advanced metachronous neoplasia in individuals with a history of colorectal neoplasia, based on a systematic review of 15 trials involving 12,234 patients.

Low-dose aspirin, while less effective than non-aspirin NSAIDs, was ranked as the safest option among the chemoprevention agents, indicating a favorable risk-to-benefit profile for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemoprevention of colorectal cancer in individuals with previous colorectal neoplasia: systematic review and network meta-analysis. Dulai, PS., Singh, S., Marquez, E., et al.[2022]

Clinicians believe that low-dose aspirin is a safe and cost-effective option for reducing the risk of colorectal cancer in adults aged 50-70, but there are barriers to implementing the new guidelines, such as uncertainty about dosage and the strength of the evidence.

General practitioners (GPs) are seen as crucial for the successful adoption of these guidelines, and support from trusted organizations like Cancer Council Australia could facilitate wider implementation in the community.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinicians' opinions on recommending aspirin to prevent colorectal cancer to Australians aged 50-70 years: a qualitative study. Milton, S., McIntosh, J., Yogaparan, T., et al.[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]

A study reanalyzing data from two Japanese clinical trials found that the effectiveness of low-dose aspirin (100 mg/day) in preventing colorectal tumors is influenced by variations in the CYP2A6 gene, which affects enzyme activity.

Participants with the wild-type CYP2A6 genotype showed reduced chemopreventive effects from aspirin, suggesting that CYP2A6 genotyping could help personalize colorectal cancer prevention strategies using aspirin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of polymorphic cytochrome P450 2A6 genotypes on chemoprevention against colorectal tumors in single Japanese cohort using daily low-dose aspirin: insights into future personalized treatments. Yamazaki, H., Shimizu, M., Otani, T., et al.[2021]

Increased physical activity and avoiding a Western pattern diet after a colorectal cancer diagnosis are linked to lower recurrence rates and better overall survival, based on prospective observational studies.

Obesity (BMI ≥35 kg/m²) is associated with a higher risk of cancer recurrence, while regular use of aspirin or COX-2 inhibitors may help reduce recurrence rates and improve vitamin D levels in colorectal cancer survivors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beyond standard adjuvant therapy for colon cancer: role of nonstandard interventions. Meyerhardt, JA.[2021]

Regular aspirin use is associated with a significant reduction in the risk of colorectal cancer and polyps, with studies indicating a risk reduction of about 50% in most cases, based on seven recent epidemiologic studies.

However, a randomized trial found that a standard dose of aspirin (325 mg every other day) did not lower colorectal cancer incidence over five years, highlighting the need for further research to clarify optimal dosing, duration, and the effects of discontinuation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aspirin and the prevention of colorectal cancer: a review of the evidence. Paganini-Hill, A.[2019]

Aspirin chemoprophylaxis, while potentially reducing colorectal cancer risk by 30%, was found to be non-cost-effective as an adjunct to screening methods like sigmoidoscopy or colonoscopy, leading to increased costs and fewer life-years gained due to complications.

The study suggests that aspirin should not replace colorectal cancer screening, and public health efforts should prioritize improving adherence to screening protocols rather than relying on aspirin for cancer prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aspirin as an adjunct to screening for prevention of sporadic colorectal cancer. A cost-effectiveness analysis. Ladabaum, U., Chopra, CL., Huang, G., et al.[2019]

A randomized trial involving 1107 patients found that a combination of calcitriol, aspirin, and calcium carbonate did not significantly reduce the recurrence of colorectal adenomas over a 3-year period, leading to the study's early termination due to futility.

The study indicated that smoking status might influence treatment effects, with nonsmokers showing a potential benefit while current smokers did not, although these interactions were not statistically significant overall.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aspirin, Calcitriol, and Calcium Do Not Prevent Adenoma Recurrence in a Randomized Controlled Trial. Pommergaard, HC., Burcharth, J., Rosenberg, J., et al.[2022]

Aspirin and NSAIDs have shown potential in preventing colorectal cancer and its precursor adenomas, but their use is complicated by significant risks, such as increased chances of hemorrhagic stroke, necessitating further research before making general recommendations.

In the meantime, a healthy lifestyle that includes a diet rich in vegetables and fiber, regular exercise, and maintaining a healthy weight is recommended for colorectal cancer prevention, as these factors have been associated with reduced risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aspirin and other nonsteroidal anti-inflammatory agents in the prevention of colorectal cancer. Sandler, RS.[2013]

In a study of 37,916 women over an average of 10.1 years, higher dietary intakes of folate and vitamin B6 were linked to a reduced risk of colorectal cancer, particularly in those not taking supplements.

Total intakes of folate and vitamin B6 did not show a significant association with colorectal cancer risk, suggesting that the source of these nutrients (dietary vs. supplements) may play a crucial role in their protective effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Folate, vitamin B6, multivitamin supplements, and colorectal cancer risk in women. Zhang, SM., Moore, SC., Lin, J., et al.[2018]

Regular use of aspirin significantly reduces the incidence of colonic adenomas and colorectal cancer, particularly when taken at high doses for more than 10 years, with relative risk reductions observed in various study types (RCTs, case-control, and cohort studies).

However, aspirin use is associated with an increased risk of gastrointestinal complications, highlighting the need to weigh the benefits against potential harms when considering aspirin for cancer prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of aspirin for primary prevention of colorectal cancer: a systematic review prepared for the U.S. Preventive Services Task Force. Dubé, C., Rostom, A., Lewin, G., et al.[2022]

References

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

Chemoprevention of colorectal cancer in individuals with previous colorectal neoplasia: systematic review and network meta-analysis. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Clinicians' opinions on recommending aspirin to prevent colorectal cancer to Australians aged 50-70 years: a qualitative study. [2021]

3. England pubmed.ncbi.nlm.nih.gov

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

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

Effects of polymorphic cytochrome P450 2A6 genotypes on chemoprevention against colorectal tumors in single Japanese cohort using daily low-dose aspirin: insights into future personalized treatments. [2021]

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

Beyond standard adjuvant therapy for colon cancer: role of nonstandard interventions. [2021]

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

Aspirin and the prevention of colorectal cancer: a review of the evidence. [2019]

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

Aspirin as an adjunct to screening for prevention of sporadic colorectal cancer. A cost-effectiveness analysis. [2019]

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

Aspirin, Calcitriol, and Calcium Do Not Prevent Adenoma Recurrence in a Randomized Controlled Trial. [2022]

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

Aspirin and other nonsteroidal anti-inflammatory agents in the prevention of colorectal cancer. [2013]

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

Folate, vitamin B6, multivitamin supplements, and colorectal cancer risk in women. [2018]

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

The use of aspirin for primary prevention of colorectal cancer: a systematic review prepared for the U.S. Preventive Services Task Force. [2022]