Atorvastatin ± Aspirin for Lynch Syndrome

Overseen By Yana Chertock, MA

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Fox Chase Cancer Center

Disqualifiers: Active cancer, Statin intolerance, others

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

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether atorvastatin, a common cholesterol-lowering drug, alone or combined with aspirin, can lower the risk of colorectal cancer in people with Lynch syndrome, a condition that increases cancer risk. Participants will take either atorvastatin alone or both atorvastatin and aspirin daily for six weeks. The trial seeks individuals with Lynch syndrome who had colorectal cancer successfully treated over a year ago. As an Early Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking research.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you have a statin intolerance or cannot take aspirin or atorvastatin, you may not be eligible to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Studies have shown that atorvastatin is generally safe. The FDA has approved it for lowering cholesterol, and most people tolerate it well. Common side effects include muscle pain, upset stomach, and headaches, while serious side effects are rare.

Research indicates that aspirin is also usually safe for people with Lynch syndrome. It has been shown to help lower the risk of colorectal cancer in these individuals. Common side effects might include an upset stomach or heartburn, but these are usually mild for most people.

Although this trial is in an early phase, both drugs are well-studied and FDA-approved for other uses, suggesting they are likely safe. Participants should discuss any concerns with their doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard care for Lynch syndrome, which typically involves regular surveillance and surgical interventions, atorvastatin is being explored for its potential to reduce cancer risk through its cholesterol-lowering properties. Researchers are excited about atorvastatin because it may offer a non-invasive preventive option, targeting inflammation and cell proliferation pathways that could contribute to cancer development in Lynch syndrome. The combination of atorvastatin with aspirin is also intriguing since aspirin is known for its anti-inflammatory effects, potentially enhancing the protective benefits against cancer.

What evidence suggests that this trial's treatments could be effective for reducing the risk of colorectal cancer in individuals with Lynch syndrome?

Research has shown that atorvastatin, a drug commonly used to lower cholesterol, may help reduce the risk of colorectal cancer in people with Lynch syndrome, a condition that increases cancer risk. Studies have found that using statins, like atorvastatin, links to a lower chance of developing certain tumors, including those related to Lynch syndrome. In this trial, some participants will receive atorvastatin alone, while others will receive a combination of atorvastatin and aspirin. Clinical trials have shown that aspirin can significantly lower the risk of colorectal cancer for people with Lynch syndrome. When used together, atorvastatin and aspirin might be even more effective in reducing this cancer risk. Early findings suggest that this combination targets specific cancer markers, potentially offering protective benefits to those at high risk. ^{1 2 6 7 8}

Who Is on the Research Team?

Michael J Hall, MD, MS

Principal Investigator

Fox Chase Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with Lynch Syndrome, a genetic condition raising colorectal cancer risk. Participants must understand English to give informed consent and have no active cancer or recent hormonal therapy. Those with statin intolerance, aspirin contraindications, or who are pregnant/breastfeeding cannot join.

Inclusion Criteria

Able to read and sign an informed consent document in English

Eligible subjects will have molecular evidence of Lynch Syndrome (mutation in MLH1, MSH2, MSH6, EPCAM or PMS2)

You had colorectal cancer in the past, but it was treated with surgery and chemotherapy over a year ago.

Exclusion Criteria

Unable to read and sign an informed consent document in English

Have active cancer or are less than 3 years post hormonal maintenance therapy for cancer

You cannot take statins or aspirin due to medical reasons.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive atorvastatin alone or with aspirin for 6 weeks. Blood and colon biopsies are obtained at Day 0 and at 6 weeks.

6 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including adverse event assessments and medication adherence.

4 weeks

2 visits (virtual)

What Are the Treatments Tested in This Trial?

Interventions

• Aspirin
• Atorvastatin

Trial Overview The study tests if Atorvastatin (a cholesterol-lowering drug), alone or combined with Aspirin (an anti-inflammatory drug), can lower the risk of colorectal cancer in individuals at high risk due to Lynch Syndrome.

How Is the Trial Designed?

Group I: Atorvastatin and Aspirin Active Control 1 Intervention

Atorvastatin (LIPITOR) 20 milligram tablet and Aspirin 325 mg tablet daily for 6 weeks

Group II: Atorvastatin Active Control 1 Intervention

Atorvastatin (LIPITOR) 20 milligram tablet daily for 6 weeks

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

Approved in European Union as Lipitor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Homozygous familial hypercholesterolemia

Approved in United States as Lipitor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Homozygous familial hypercholesterolemia
• Prevention of cardiovascular disease

Approved in Canada as Lipitor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Homozygous familial hypercholesterolemia
• Prevention of cardiovascular disease

Approved in Japan as Lipitor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Homozygous familial hypercholesterolemia

Approved in China as Lipitor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Homozygous familial hypercholesterolemia

Approved in Switzerland as Lipitor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Homozygous familial hypercholesterolemia

Who Is Running the Clinical Trial?

Fox Chase Cancer Center

Lead Sponsor

Trials

236

Recruited

39,300+

Prevent Cancer Foundation

Collaborator

Trials

7

Recruited

1,500+

Published Research Related to This Trial

Atorvastatin effectively lowers total cholesterol, LDL-cholesterol, and triglycerides while increasing HDL-cholesterol, making it more effective than other statins in patients with coronary heart disease (CHD).

It is well tolerated with mild and transient side effects, and long-term studies are ongoing to assess its impact on serious cardiac events and mortality, confirming its role as a first-line treatment for various patients at risk for CHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atorvastatin: an updated review of its pharmacological properties and use in dyslipidaemia. Malhotra, HS., Goa, KL.[2018]

Lynch syndrome (LS) patients have a high lifetime risk of colorectal cancer (CRC), and while low-dose aspirin has shown some promise in reducing sporadic adenomas and CRC risk, recent large trials have not confirmed its protective effect in all populations.

The AAS-Lynch trial is currently investigating whether daily aspirin therapy (100 or 300 mg) can effectively reduce the occurrence or recurrence of colorectal adenomas in LS patients under 75 years old, following mixed results from previous studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of chemoprevention by low-dose aspirin of new or recurrent colorectal adenomas in patients with Lynch syndrome (AAS-Lynch): study protocol for a multicenter, double-blind, placebo-controlled randomized controlled trial. Soualy, A., Deutsch, D., Benallaoua, M., et al.[2021]

Atorvastatin is a highly effective statin that significantly reduces low-density lipoprotein cholesterol (LDL-C) and total cholesterol levels in patients with high cholesterol, achieving better results than other statins.

While atorvastatin is generally safe, it can cause mild side effects like gastrointestinal issues and muscle pain, and it may require monitoring for liver enzyme levels, especially due to its metabolism through the CYP3A4 pathway.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atorvastatin: a hydroxymethylglutaryl-coenzyme A reductase inhibitor. Malinowski, JM.[2022]

Atorvastatin is a highly effective statin that significantly lowers LDL and total cholesterol levels, and it is the first statin proven to reduce triglycerides in patients with high triglyceride levels.

In addition to its cholesterol-lowering effects, atorvastatin has beneficial non-lipid effects, such as improving blood vessel function and reducing inflammation, although clinical trial evidence is still limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atorvastatin. Wierzbicki, AS.[2019]

A survey of 672 GPs in England and Wales found that 80.4% were willing to prescribe aspirin for colorectal cancer prevention in patients with Lynch syndrome, indicating a generally positive attitude towards the recommendation.

Providing additional information about NICE guidelines, trial results, and risk-benefit comparisons did not significantly influence GPs' willingness to prescribe aspirin, suggesting that other strategies may be needed to enhance prescribing practices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GPs' willingness to prescribe aspirin for cancer preventive therapy in Lynch syndrome: a factorial randomised trial investigating factors influencing decisions. Lloyd, KE., Hall, LH., Ziegler, L., et al.[2023]

Atorvastatin effectively lowers total cholesterol, LDL-cholesterol, and triglyceride levels in patients with hypercholesterolaemia and hypertriglyceridaemia, showing greater reductions compared to other statins like lovastatin and simvastatin.

While atorvastatin has a similar adverse event profile to other statins, it is particularly effective for patients with familial hypercholesterolaemia and may be suitable for treating combined hyperlipidaemia due to its significant LDL-cholesterol reduction capabilities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atorvastatin. A review of its pharmacology and therapeutic potential in the management of hyperlipidaemias. Lea, AP., McTavish, D.[2018]

Atorvastatin effectively lowers LDL cholesterol levels by 41% to 61%, depending on the dosage, through its mechanism of inhibiting HMG Co-A reductase, which increases LDL receptors in the liver.

The safety profile of atorvastatin is favorable, with only transient gastrointestinal side effects and rare changes in liver tests or muscle enzymes, making it a viable option for treating various forms of hypercholesterolemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Atorvastatin (Lipitor)]. Carpentier, Y., Ducobu, J., Sternon, J.[2018]

In a long-term study involving 861 participants with Lynch syndrome, daily aspirin significantly reduced the risk of developing colorectal cancer, with a hazard ratio of 0.65 compared to placebo, indicating a 35% lower risk.

While aspirin did not show a significant effect on non-colorectal cancers associated with Lynch syndrome, the overall risk for all Lynch syndrome cancers combined was reduced in those taking aspirin, suggesting potential broader benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cancer prevention with aspirin in hereditary colorectal cancer (Lynch syndrome), 10-year follow-up and registry-based 20-year data in the CAPP2 study: a double-blind, randomised, placebo-controlled trial. Burn, J., Sheth, H., Elliott, F., et al.[2023]

Aspirin is recommended for people with Lynch syndrome to lower colorectal cancer risk, but both patients and healthcare providers face challenges in decision-making regarding its use, particularly concerning potential benefits and harms.

Healthcare providers, especially general practitioners, need more guidance and clarity on prescribing aspirin for preventive therapy, as many are unfamiliar with its use and patients often lack information on how to proceed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Barriers and facilitators to using aspirin for preventive therapy: a qualitative study exploring the views and experiences of people with Lynch syndrome and healthcare providers. Lloyd, KE., Foy, R., Hall, LH., et al.[2022]

Carriers of Lynch syndrome mutations have a higher risk of certain cancers, but daily aspirin consumption may help reduce this risk, highlighting the importance of educating these individuals about potential preventive measures.

An educational leaflet developed for Lynch syndrome carriers was well-received, with over 70% of participants rating it positively, and 91% reporting improved understanding of aspirin's benefits and usage, indicating its potential to enhance patient-provider discussions on cancer risk reduction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Risk-Reducing Effect of Aspirin in Lynch Syndrome Carriers: Development and Evaluation of an Educational Leaflet. Kaur, R., McDonald, C., Meiser, B., et al.[2023]

Aspirin has been shown to significantly reduce the risk of colorectal cancer (CRC) in individuals with Lynch Syndrome, based on the CAPP2 study involving 861 participants over a median treatment time of 2 years.

Current guidelines recommend discussing low-dose aspirin as a preventive measure for CRC with Lynch syndrome carriers, as ongoing studies (CAPP3) are exploring its effectiveness at lower doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aspirin Colorectal Cancer Prevention in Lynch Syndrome: Recommendations in the Era of Precision Medicine. Serrano, D., Patrignani, P., Stigliano, V., et al.[2023]

A majority of clinicians (76%) believe that aspirin is an effective risk-reducing medication for patients with Lynch Syndrome, and those who feel confident discussing it are more likely to recommend it to their patients.

There is a significant need for patient educational materials about aspirin, as 87% of health professionals reported this necessity, which could help improve communication and consistency in care for Lynch Syndrome patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exploring clinicians' attitudes about using aspirin for risk reduction in people with Lynch Syndrome with no personal diagnosis of colorectal cancer. Chen, Y., Peate, M., Kaur, R., et al.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04379999?cond=Lynch%20syndrome&rank=7

NCT04379999 | Atorvastatin ± Aspirin in Lynch Syndrome ... Rate of adherence of healthy patients with Lynch Syndrome to a 6-week of the treatment regimen (atorvastatin ± aspirin). Medication Adherence to the 6-week ...

2. foxchase.org foxchase.org/news/2021-03-03-researchers-awarded-grant-to-study-use-of-lipitor-in-patients-with-lynch-syndrome

Researchers Awarded Grant to Study Use of Lipitor in ... This study, “Impact of Atorvastatin With or Without Aspirin on Colorectal Biomarkers in Patients with Lynch Syndrome: A Pilot Study,” is ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04379999

NCT04379999 | Atorvastatin ± Aspirin in Lynch Syndrome ... Rate of adherence of healthy patients with Lynch Syndrome to a 6-week of the treatment regimen (atorvastatin ± aspirin). Medication Adherence to the 6-week ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8770588/

Statin use is associated with a reduced incidence ... Chemoprevention with statins could potentially be targeted to those at risk of developing SMAD4 high tumours such as patients with Lynch ...

5. facingourrisk.org facingourrisk.org/research-clinical-trials/study/144/atorvastatin-aspirin-for-colorectal-cancer-prevention-for-people-with-lynch-syndrome

Atorvastatin ± Aspirin for Colorectal Cancer Prevention for ... Giving atorvastatin and aspirin may work better at reducing the risk of colorectal cancer (CRC) in high-risk individuals with Lynch syndrome. This Study is Open ...

6. withpower.com withpower.com/trial/early-phase-1-colorectal-neoplasms-hereditary-nonpolyposis-8-2018-4ed6a

Atorvastatin ± Aspirin for Lynch Syndrome Is it safe to use aspirin for Lynch Syndrome? Aspirin is generally considered safe for people with Lynch Syndrome, as it has been shown to reduce the risk of ...

7. ahajournals.org ahajournals.org/doi/10.1161/atv.0000000000000073

Statin Safety and Associated Adverse Events: A Scientific ... ... safety data for lovastatin, simvastatin, pravastatin, atorvastatin, and rosuvastatin. ... Taylor PJ, Kubler PA, Lynch SV, Allen J, Butler M, ...

8. trialx.com trialx.com/clinical-trials/listings/239064/atorvastatin-aspirin-in-lynch-syndrome-syndrome/?&radius=50

Atorvastatin ± Aspirin in Lynch Syndrome Syndrome Eligible subjects will have molecular evidence of Lynch Syndrome (mutation in MLH1, MSH2, MSH6, EPCAM or PMS2); History of colorectal cancer if ...