Atorvastatin for Hearing Loss in Head and Neck Cancer

Recruiting at 3 trial locations

Overseen By Lisa L Cunningham, Ph.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Institute on Deafness and Other Communication Disorders (NIDCD)

Must be taking: Statins

Must not be taking: Cimetidine, Spironolactone, others

Disqualifiers: Liver disease, Kidney disease, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 5

Duration: 12 weeks

224 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether atorvastatin, a cholesterol-lowering drug, can prevent hearing loss caused by cisplatin, a chemotherapy drug used in head and neck cancer treatment. Participants will take either atorvastatin or a placebo during their cancer treatment to determine its effectiveness in protecting hearing. Individuals with squamous cell carcinoma of the head and neck who plan to receive cisplatin and radiation therapy might be suitable candidates for this trial. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently taking a statin drug or certain other medications like cimetidine or spironolactone. It's best to discuss your specific medications with the study team.

Is there any evidence suggesting that atorvastatin is likely to be safe for humans?

Research has shown that atorvastatin might help reduce hearing loss caused by cisplatin, a cancer treatment drug. Studies have found that atorvastatin is usually safe and may lessen hearing loss in adults receiving cisplatin for head and neck cancer.

While atorvastatin is normally used to lower cholesterol, it has also been studied for its potential to protect hearing. Participants in earlier studies did not experience major side effects, suggesting that atorvastatin is generally well-tolerated. This information could reassure those considering participation in a trial involving atorvastatin. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for hearing loss?

Unlike standard treatments for hearing loss in head and neck cancer, which typically focus on managing symptoms or protecting the ear from further damage, atorvastatin offers a novel approach by potentially protecting the inner ear from damage caused by chemotherapy. This drug, commonly known for lowering cholesterol, may reduce inflammation and oxidative stress in the ear, both of which are believed to contribute to hearing loss. Researchers are excited because, if effective, atorvastatin could provide a protective benefit against hearing loss, offering hope for preserving hearing in patients undergoing cancer treatment.

What evidence suggests that atorvastatin might be an effective treatment for hearing loss?

This trial will compare atorvastatin with a placebo to evaluate its effectiveness in preventing hearing loss in patients with head and neck cancer. Research has shown that atorvastatin might help prevent hearing loss caused by the cancer treatment drug cisplatin. In one study involving adults with head and neck cancer, those taking atorvastatin experienced significantly less hearing loss, with only 9.7% affected, compared to those not taking the drug. Another study found that people using atorvastatin were less likely to develop hearing loss than those who did not use it. These findings suggest that atorvastatin could help protect hearing in individuals undergoing certain cancer treatments. ^{1 5 6 7 8}

Who Is on the Research Team?

Lisa L Cunningham, Ph.D.

Principal Investigator

National Institute on Deafness and Other Communication Disorders (NIDCD)

Are You a Good Fit for This Trial?

This trial is for adults with squamous cell carcinoma of the head and neck who will undergo cisplatin-based chemotherapy and radiation. They must be able to take oral medication, agree to use effective contraception if applicable, and not be on statins or have certain medical conditions that could interfere with the study.

Inclusion Criteria

I have squamous cell carcinoma of the head and neck and will be treated with specific chemotherapy and radiation.

Your blood test results for AST, ALT, CPK, and creatinine are too low.

For females of reproductive potential: use of highly effective contraception for at least 1 month prior to enrollment and agreement to use such a method during study participation and for an additional 8 weeks after the end of atorvastatin administration

Exclusion Criteria

Known allergic reactions to components of atorvastatin or the placebo

Pregnancy, lactation, or plan to become pregnant

I am currently taking a statin medication.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Treatment

Participants receive cisplatin-based chemotherapy and radiation, with atorvastatin or placebo administered daily

12 weeks

3 visits (in-person) for hearing evaluation, 2 visits for blood tests

Follow-up

Participants are monitored for safety and effectiveness after treatment, including hearing tests and chart reviews

2 years

1 visit (in-person) within 3 months, 1 visit (in-person) within 2 years

Long-term follow-up

Long-term follow-up includes a chart review 2 years after participants complete their cisplatin therapy

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Atorvastatin
• Placebo

Trial Overview The trial is testing whether atorvastatin can prevent hearing loss in patients treated with cisplatin for head and neck cancer. Participants are randomly assigned to receive either atorvastatin or a placebo daily during treatment and for three months after.

How Is the Trial Designed?

Group I: 1 Experimental Treatment 2 Interventions

Atorvasatatin (40 mg)

Group II: 2 Placebo Group 1 Intervention

Placebo

Who Is Running the Clinical Trial?

National Institute on Deafness and Other Communication Disorders (NIDCD)

Lead Sponsor

Trials

377

Recruited

190,000+

Published Research Related to This Trial

Statin drugs, commonly used for lowering cholesterol, may improve survival rates and reduce treatment-related toxicities in patients with head and neck squamous cell carcinoma (HNSCC), based on a review of preclinical and clinical studies.

Due to their affordability and safety profile, statins are suggested as a promising adjunctive therapy in HNSCC treatment, warranting further research to understand their mechanisms and enhance patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repurposing Statin Drugs to Decrease Toxicity and Improve Survival Outcomes in Head and Neck Cancer. Bourguillon, RO., Stokes, WA., Dorth, J., et al.[2022]

In a study of 97,252 head and neck cancer patients, those on statin medication had a significantly higher five-year survival rate of 75.19% compared to 70.48% for those not on statins.

Statin use was associated with a reduced risk of death, with a hazard ratio of 0.80, suggesting that statins may improve overall survival in head and neck cancer patients, although the study's retrospective nature means results should be interpreted cautiously.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Statin Medication Improves Five-Year Survival Rates in Patients with Head and Neck Cancer: A Retrospective Case-Control Study of about 100,000 Patients. Wüster, J., Heiland, M., Nahles, S., et al.[2023]

In a study of 277 adults treated with cisplatin for head and neck cancer, those taking atorvastatin experienced significantly less hearing loss (9.7%) compared to nonstatin users (29.4%), indicating atorvastatin's protective effect against cisplatin-induced ototoxicity.

Atorvastatin users were found to be 53% less likely to develop significant hearing loss from cisplatin, with no difference in three-year survival rates between atorvastatin and nonstatin users, suggesting atorvastatin's efficacy in preserving hearing without compromising cancer treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atorvastatin is associated with reduced cisplatin-induced hearing loss. Fernandez, KA., Allen, P., Campbell, M., et al.[2021]

Head and neck cancer (HNC) patients with hyperlipidemia who were taking statins showed significantly better overall survival (73.0%) and cancer-specific survival (81.2%) compared to those not taking statins (61.7% overall survival and 69.2% cancer-specific survival) and those without hyperlipidemia (58.6% overall survival and 69.1% cancer-specific survival).

Statin use in HNC patients was associated with improved survival outcomes even after controlling for various factors, indicating that statins may serve as a beneficial adjunct treatment in managing head and neck cancer, with no significant difference in toxicity-related events among the groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Statin use associated with improved overall and cancer specific survival in patients with head and neck cancer. Gupta, A., Stokes, W., Eguchi, M., et al.[2020]

Ototoxicity, which can lead to irreversible hearing loss, affects 30-40% of patients undergoing radiotherapy for head and neck cancer, highlighting the need for effective prevention strategies.

Primary prevention measures include limiting radiation doses to the cochlea and considering alternative chemotherapy options like carboplatin or cetuximab to reduce the risk of hearing loss, along with monitoring and evaluating individual risk factors before treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Ototoxicity in head and neck cancers after radiotherapy and chemoradiotherapy: From primary prevention to tertiary prevention]. Espenel, S., Garcia, MA., Guy, JB., et al.[2017]

Lovastatin has been shown to significantly reduce cisplatin-induced hearing loss in adult mice, suggesting its potential as a protective agent against ototoxicity caused by cisplatin treatment.

The protective effect of lovastatin was found to be more pronounced in female mice, indicating that sex differences may influence the required dosage for effective protection, which is important for future clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lovastatin protects against cisplatin-induced hearing loss in mice. Fernandez, K., Spielbauer, KK., Rusheen, A., et al.[2021]

This systematic review and meta-analysis evaluated the protective effects of metformin, statins, and anti-inflammatory drugs on head and neck cancer, highlighting their potential roles in cancer prevention.

The findings suggest that these medications may offer beneficial effects in reducing the risk or severity of head and neck cancer, although specific efficacy details and mechanisms were not provided in the abstract.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Limited Evidence Suggests Metformin Might Be Beneficial to Reduce Head and Neck Cancer Risk and Increase Overall Survival, While Any Benefit With Antiinflammatory Drugs Is Inconsistent. Veitz-Keenan, A., Silvestre Calle, TD., Bergamini, M.[2020]

In a study of 4669 head and neck cancer patients, those who used statins showed a trend towards reduced recurrence rates at 3 and 5 years compared to matched controls, with risk ratios of 0.79 and 0.89, respectively.

However, the association was not statistically significant, indicating that while there may be a potential benefit of statin use in reducing HNC recurrence, further research is needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of statin use on head and neck cancer prognosis in a multicenter study using a Common Data Model. Seol, S., Choi, JR., Choi, B., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7773379/

Atorvastatin is associated with reduced cisplatin-induced ... Our data indicate that atorvastatin use is associated with reduced incidence and severity of cisplatin-induced hearing loss in adults being treated for head and ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.TPS12153

Randomized, placebo-controlled trial of atorvastatin to ... An adjusted odds ratio analysis indicated that atorvastatin users are significantly less likely to develop hearing loss versus statin non-users ...

3. withpower.com withpower.com/trial/phase-3-deafness-9-2021-de66c

Atorvastatin for Hearing Loss in Head and Neck Cancer In a study of 277 adults treated with cisplatin for head and neck cancer, those taking atorvastatin experienced significantly less hearing loss (9.7%) compared ...

4. clinicaltrial.be clinicaltrial.be/en/details/19788?per_page=100&recruiting=1&enrolling_by_invitation=1&active_not_recruiting=1&not_yet_recruiting=0&completed=0&only_recruiting=0&only_eligible=0

Atorvastatin to Reduce Cisplatin-Induced Hearing Loss ... Phase II Interventional Study Using Atorvastatin to Reduce Cisplatin-Induced Hearing Loss Among Individuals With Head and Neck Cancer.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04915183?tab=history&a=1

Record History | ver. 1: 2021-06-04 | NCT04915183 The cholesterol-lowering drug atorvastatin has the potential to reduce the incidence and severity of hearing loss, as evidenced by our preclinical data in mice ...

6. centerwatch.com centerwatch.com/clinical-trials/listings/NCT04915183/atorvastatin-to-reduce-cisplatin-induced-hearing-loss-among-individuals-with-head-and-neck-cancer

Atorvastatin to Reduce Cisplatin-Induced Hearing Loss ... Atorvastatin is a drug used to treat high cholesterol. It might reduce the risk of cisplatin-induced hearing loss.

7. nature.com nature.com/articles/s41598-021-93916-z

Association between statin medication and hearing ... A recent clinical study demonstrated the otoprotective effects of atorvastatin in patients treated with cisplatin for head and neck cancer.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT06553157

Study Details | NCT06553157 | Statins Effect on Incidence ... The incidence of ototoxicity induced by cisplatin has been estimated to be 36% of adult patients with cancer and 40%-60% of pediatric patients. Ototoxicity can ...