Atorvastatin for Cancer

Overseen By KUCC Navigation

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Joaquina Baranda

Must not be taking: Investigational agents, Statins, Myopathy drugs

Disqualifiers: Pregnancy, Squamous cell cancer, 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: Unknown

Duration: 1-4 weeks

50 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a window-of-opportunity trial to determine if atorvastatin given for 1 to 4 weeks at a dose of 80 milligrams per day (mg/day) is sufficient to decrease the level of conformational mutant tumor protein 53 (p53) in malignant diseases (solid tumor and relapsed Acute Myeloid Leukemia (AML)).

Will I have to stop taking my current medications?

The trial requires that you have not used systemic therapy like chemotherapy, immunotherapy, or hormonal therapy within the last 30 days. Also, you cannot use other investigational agents or statins in the past 30 days. If you're on these medications, you may need to stop them before joining the trial.

What data supports the effectiveness of the drug Atorvastatin for cancer treatment?

Research suggests that atorvastatin, a drug commonly used to lower cholesterol, may help reduce the growth and spread of certain cancer cells, such as breast and prostate cancer cells, by affecting their ability to move and invade other tissues. ^{1 2 3 4 5}

Is atorvastatin generally safe for humans?

Atorvastatin, also known as Lipitor, is considered safe and has a good safety profile when used to lower cholesterol levels. It has been studied in various conditions, including cancer, and is known for its non-lipid-lowering effects like improving blood vessel function and reducing inflammation. ^{1 5 6 7 8}

How does the drug atorvastatin differ from other treatments for cancer?

Atorvastatin, commonly used to lower cholesterol, is being explored for its potential to inhibit cancer cell growth and migration, particularly in breast cancer, by targeting the mevalonate pathway and affecting protein prenylation and Akt signaling, which are not typical targets of standard cancer treatments. ^{1 9 10 11 12}

Research Team

Joaquina Baranda, MD

Principal Investigator

The University of Kansas Cancer Center

Eligibility Criteria

This trial is for adults with various cancers, including solid tumors and blood cancers like relapsed AML, who are scheduled for surgery or between treatments. Participants must have TP53-positive or negative tumors, not be on recent cancer therapies, and have good organ function. Pregnant women can't join; neither can those with certain health conditions like active liver disease or a history of rhabdomyolysis.

Inclusion Criteria

A negative urine or serum pregnancy test within 7 days before Day 1 dose of study medication, if female participant is of childbearing potential.

I understand the study and can sign the consent myself.

My tumor is positive for the TP53 protein.

Exclusion Criteria

Hypersensitivity to atorvastatin or any component of the formulation

I had cancer before, but it's been in complete remission for over 2 years and I don't need treatment now.

I have been diagnosed with squamous cell cancer of the oropharynx.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive atorvastatin at a dose of 80 mg/day for 1 to 4 weeks

1-4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Atorvastatin

Trial Overview The trial tests if Atorvastatin (80 mg/day) taken for 1-4 weeks affects the levels of mutant p53 protein in malignant diseases. It's designed to see if this common cholesterol-lowering drug could help treat different types of cancer by targeting a specific protein involved in tumor growth.

Participant Groups

Group I: Atorvastatin Experimental Treatment 1 Intervention

Atorvastatin 80 milligrams (mg) per day, orally for 1 - 4 weeks before surgery (surgery not part of clinical trial)

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?

Joaquina Baranda

Lead Sponsor

Trials

1

Recruited

50+

Findings from Research

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]

Atorvastatin effectively reduced serum cholesterol levels in mice but did not decrease the size or number of chemically induced liver tumors, indicating it does not inhibit hepatocellular carcinoma (HCC) growth.

The study challenges the idea that long-term atorvastatin use may protect against HCC, as it showed no beneficial effects on tumor growth despite changes in drug uptake transporters in tumor tissue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemically induced mouse liver tumors are resistant to treatment with atorvastatin. Braeuning, A., Bucher, P., Hofmann, U., et al.[2022]

In a study using rat models, atorvastatin and lovastatin did not significantly reduce the incidence of estrogen receptor-positive mammary cancers, indicating limited efficacy in cancer prevention.

While statins did not enhance the effectiveness of tamoxifen or bexarotene in reducing cancer multiplicity, they were able to lower triglyceride levels in bexarotene-treated rats, suggesting a potential role in managing lipid levels rather than directly preventing cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lack of efficacy of the statins atorvastatin and lovastatin in rodent mammary carcinogenesis. Lubet, RA., Boring, D., Steele, VE., et al.[2018]

References

1. Thailand pubmed.ncbi.nlm.nih.gov

Atorvastatin Inhibits Viability and Migration of MCF7 Breast Cancer Cells. [2022]

2. Korea (South) pubmed.ncbi.nlm.nih.gov

Atorvastatin regulates the migration and invasion of prostate cancer through the epithelial-mesenchymal transformation and matrix metalloproteinase pathways. [2022]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Statins and risk of breast cancer recurrence. [2022]

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

Protective Effects of Statins in Cancer: Should They Be Prescribed for High-Risk Patients? [2022]

5. Germany pubmed.ncbi.nlm.nih.gov

Efficacy and safety profile of statins in patients with cancer: a systematic review of randomised controlled trials. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Atorvastatin. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Chemically induced mouse liver tumors are resistant to treatment with atorvastatin. [2022]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Phase I biomarker modulation study of atorvastatin in women at increased risk for breast cancer. [2018]

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

Concomitant attenuation of HMG-CoA reductase expression potentiates the cancer cell growth-inhibitory effect of statins and expands their efficacy in tumor cells with epithelial characteristics. [2023]

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

Lipophilic statins limit cancer cell growth and survival, via involvement of Akt signaling. [2023]

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

Lack of efficacy of the statins atorvastatin and lovastatin in rodent mammary carcinogenesis. [2018]

12. England pubmed.ncbi.nlm.nih.gov

Induction of 3-hydroxy-3-methylglutaryl-CoA reductase mediates statin resistance in breast cancer cells. [2020]