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Hearing LossPhase 2NCT04915183

Atorvastatin to Reduce Cisplatin-Induced Hearing Loss Among Individuals With Head and Neck Cancer

A Phase 2 study testing Atorvastatin in people with Hearing Loss and Head and Neck Cancer, run by National Institute on Deafness and Other Communication Disorders (NIDCD) at 5 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

Background: Cisplatin is used to treat head and neck cancer. People who take this drug are at risk for hearing loss. Atorvastatin is a drug used to treat high cholesterol. It might reduce the risk of cisplatin-induced hearing loss. Read more about this study

Who is it for?
Ages 18 to 100 years
Conditions the study is for
Hearing Loss, Head and Neck Cancer
What is being tested?
Atorvastatin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
224 participants
Where
5 sitesUnited States
Study dates
10 Jul 2024to 31 Aug 2030
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 100 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • In order to be eligible to participate in this study, an individual must meet all of the following criteria evaluated by the study team, including an on-site oncologist:
  • Willingness and ability to comply with and participate in all study procedures and availability for the duration of the study
  • Ability to provide consent and provision of signed and dated informed consent form
  • Adult subjects, aged >=18
  • Diagnosed with squamous cell carcinoma of the head and neck, confirmed by a pathologic review of surgical or biopsy specimen(s), who meet standard clinical and laboratory criteria and will undergo treatment with concomitant cisplatin-based chemotherapy and radiation with curative intent or treatment with neoadjuvant chemotherapy (NAC). This includes subjects who will be treated with either intensity-modulated radiation therapy (IMRT) or proton radiotherapy, with planned dose to the cochlea <35 Gy (to limit confounding effects of radiation64-67). Patients receiving immunotherapy in addition to cisplatin chemoradiation are eligible. Subjects treated with either high-dose cisplatin (typically 100 mg/m^2 x 2-3 doses every three weeks) or low-dose, weekly cisplatin (typically 40 mg/m^2 x 6-7 doses weekly) may enroll. Cisplatin in the neo-adjuvant setting may be given within a combination chemotherapy regimen (e.g TPF= Docetaxel, Cisplatin and 5FU or DC = Docetaxel Cisplatin)
  • Subjects must have hearing thresholds at or better than 70 dB HL at 1, 2, and 4 kHz in at least one ear at the time of their baseline audiogram. CTCAE criteria (primary endpoint) and ASHA criteria (secondary endpoint) are based on changes in hearing in at
Show all 10Show fewer
  • least one ear with one ototoxicity event/grade assigned per person.
  • Baseline laboratory tests with lab values <1.5x the upper limit of normal: aspartate aminotransferase (AST or SGOT); alanine aminotransferase; creatine phosphokinase, creatinine
  • Ability to take oral medication by mouth or by feeding tube and willingness to adhere to the daily atorvastatin or placebo regimen
  • 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

Who cannot join

  • An individual who meets any of the following criteria will be excluded from participation in this study:
  • Subjects currently taking a statin drug
  • Subjects with bilateral flat, Type B tympanogram
  • Subjects with bilateral cochlear implants
  • Pre-existing liver or kidney disease that in the opinion of the investigator would interfere with taking Atorvastatin 40 mg daily.
  • Subjects with a history of prior treatment with cisplatin chemotherapy
Show all 13Show fewer
  • Staff members of the NIDCD Sections and of the lead site investigators headed by the PIs
  • Children will be excluded because HNSCC in children under age 18 is exceedingly rare
  • Current use of cimetidine, spironolactone, ketoconazole, cyclosporine, protease inhibitors, gemfibrozil, clarithromycin or itraconazole
  • Pregnancy, lactation, or plan to become pregnant
  • Known allergic reactions to components of atorvastatin or the placebo
  • Other severe or unstable medical conditions which clinical site PI believes increase risk to safety or ability to complete study
  • Expected concomitant use of aminoglycoside antibiotics

Trial locations and contacts

5 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Katharine A Fernandez, Au.D. contact

(240) 215-7152

katharine.fernandez@nih.gov

Lisa L Cunningham, Ph.D. contact

(301) 443-2766

cunninghamll@mail.nih.gov

5 sites in 1 country

United States5 sites, 5 recruiting
  • Winship Cancer Institute at Emory University

    Atlanta, Georgia, 30322

    Nicole Schmitt, 404-778-0278, nicole.cherie.schmitt@emory.edu

    Recruiting
  • University of Maryland Medical Center

    Baltimore, Maryland, 21201

    Adam Kaufman, 667-214-2382, adam.kaufman@som.umaryland.edu

    Recruiting
  • National Institutes of Health Clinical Center

    Bethesda, Maryland, 20892

    For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR), 800-411-1222 ext. TTY8664111010, prpl@cc.nih.gov

    Recruiting
  • Inova Schar Cancer Center

    Fairfax, Virginia, 22031

    John Deeken, M.D., 571-472-0218, john.deeken@inova.org

    Recruiting
  • Wilmot Cancer Institute at the University of Rochester Medical Center in New Yor

    Rochester, New York, 14642

    Shawn Newlands, 585-275-5823, Shawn_Newlands@urmc.rochester.edu

    Recruiting

Other trials in United States

About this study

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

Background:

Cisplatin is used to treat head and neck cancer. People who take this drug are at risk for hearing loss. Atorvastatin is a drug used to treat high cholesterol. It might reduce the risk of cisplatin-induced hearing loss.

Read more

Objective:

To find out if atorvastatin reduces hearing loss in people treated with cisplatin and radiation.

Eligibility:

People ages 18 and older with squamous cell carcinoma of the head and neck who will undergo treatment with cisplatin-based chemotherapy and radiation

Design:

Participants will be screened with their medical records.

Participants currently taking a cholesterol-lowering statin medication are invited to participate in the observational arm of the study. Those not taking such a medication are invited to participate in the interventional arm of the study.

All participants will have 3 study visits for the purpose of evaluating hearing. One before starting cisplatin treatment, one within 3 months of completing cancer treatment, and one within 2 years of completing cancer treatment. They will have tympanograms. A small flexible tip will be placed in the ear canal. A puff of air will be delivered to assess mobility of the ear drum. They will have hearing tests. They will wear headphones. They will listen to tones that vary in loudness. They will be asked to indicate when they hear a sound. They will complete 3 questionnaires at the time of each hearing test.

Participants will have 2 visits for blood tests. These will occur upon consent and 12 weeks after. They will be randomly assigned to take the study drug or placebo orally, once daily. They will take it during cisplatin treatment and for 3 months after treatment.

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

Read the detailed description

Study Description: Individuals undergoing cisplatin-based chemotherapy are at risk for developing significant, permanent hearing loss. 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 and our retrospective data in humans. Here we will compare hearing changes between subjects on a concurrent 40 mg daily dose of atorvastatin vs. a placebo among individuals undergoing cisplatin-based chemotherapy to treat head and neck cancer.

Objectives:

Primary Objective: To determine the effectiveness of atorvastatin (40 mg) in subjects treated with cisplatin-based chemotherapy for head and neck squamous cell carcinoma (HNSCC) at reducing moderate changes in hearing sensitivity relative to baseline, as defined by CTCAEv5.0 Grade>=2 criteria.

Secondary Objectives:

  • To determine disease-free survival and overall survival in subjects undergoing cisplatin-based chemotherapy.
  • To determine whether atorvastatin increases grade 3-5 treatment emergent adverse events versus placebo
  • To determine the effectiveness of atorvastatin (40 mg) at reducing changes in hearing sensitivity relative to baseline, as defined by ASHA criteria, in subjects treated with cisplatin- based chemotherapy for head and neck squamous cell carcinoma (HNSCC).

Endpoints:

Primary Endpoint: The incidence of hearing loss at 12 +/-4 weeks after completion of cisplatin-based chemotherapy). Hearing loss will be defined according to CTCAEv5.0 Grade >=2 criteria based on changes in sensitivity relative to baseline, in at least one ear, across 1, 2, 3, 4, 6 and 8 kHz and will be compared in subjects taking atorvastatin (40 mg) vs. subjects taking placebo.

Secondary Endpoints:

  • Overall and disease-free survival at 2 years after cisplatin-based chemotherapy. Overall survival and disease-free median survival will be compared between subjects taking atorvastatin (40 mg) vs. those taking placebo.
  • Incidence of new CTCAEv5.0 grade > 3 AEs through 12 weeks after chemotherapy in the placebo and atorvastatin arms.
  • Incidence of hearing loss at 12 +/- 4 weeks after completion of cisplatin-based chemotherapy. Hearing loss will be defined according to ASHA criteria based on changes in sensitivity relative to baseline, in at least one ear, across 1, 2, 3, 4, 6, 8, 10, and 12.5 kHz and will be compared in subjects taking atorvastatin (40 mg) vs. subjects taking placebo.
Being tested
Placebo, Atorvastatin
Keywords
Audiogram, Statin, Chemotherapy, Squamous Cell Carcinoma
Medical subject headings
Hearing Loss, Head and Neck Neoplasms, Carcinoma, Squamous Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PlaceboOther

    Placebo will be formulated to also contain a white powder such that the atorvastatin and placebo are indistinguishable even if a capsule is opened.

  • AtorvastatinDrug

    Subjects will be provided with atorvastatin (40 mg) or placebo to be taken daily by mouth or by feeding tube. The tablets may be taken whole or crushed according to patient swallowing capabilities and preference.

Study groups in NCT04915183
Study groupRoleWhat they receive
1ExperimentalAtorvasatatin (40 mg)
Receives: Drug: Atorvastatin
2Placebo comparatorPlacebo
Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. To determine the effectiveness of atorvastatin (20 mg) at reducing the incidence and severity of cisplatin-induced hearing loss in patients with head and neck squamous cell carcinoma (HNSCC).

    The primary endpoint is the change in hearing sensitivity (as measured by pure-tone audiometry) between the pre-treatment (before cisplatin therapy) hearing test and the post-treatment (after completion of cisplatin therapy) audiogram. Hearing loss will be defined according to CTCAE criteria and will be compared in subjects taking atorvastatin vs. subjects not taking any statin drug. Hearing sensitivity will be compared between audiograms collected at baseline (prior to treatment) to a repeated audiogram at the end of treatment (within 2-4 months of cessation of cisplatin administration).

    Measured: Baseline (prior to treatment) to a repeated audiogram at the end of treatment (within 2-4 months of cessation of cisplatin administration).

Secondary outcomes (3)
  1. To examine the extent to which atorvastatin 40 mg alters overall survival and disease-free survival.

    It is important to confirm that atorvastatin use does not reduce overall response, survival or disease- free survival in subjects with HNSCC. To date, only two retrospective studies have compared survival in HNSCC subjects taking statins.

    Measured: The overall survival and disease-free survival will be assessed at 3 months, 1 and 2 years after cisplatin-based CRT. Overall complete clinical response, comparing subjects taking atorvastatin (40 mg) vs those taking placebo.

  2. To compare the incidence of grade (Bullet)3 AEs through 4 weeks after CRT with atorvastatin versus placebo.

    It is important to confirm that atorvastatin does not increase the overall toxicity associated with CRT.

    Measured: Another secondary endpoint will be the incidence of grade (Bullet)3 AEs, which are expected to occur with CRT but rarely with atorvastatin.

  3. To determine the effectiveness of atorvastatin (40 mg) at reducing changes in hearing sensitivity relative to baseline, as defined by ASHA criteria, in subjects treated with cisplatin- based CRT for head and neck squamous cell carcinoma (HNSCC).

    The American Speech-Langauge-Hearing Association (ASHA) ototoxicity criteria can be used for early detection based on changes in hearing sensitivity in extended high frequencies (>8 kHz). While ASHA does not assign grades to indicate severity, it may provide early diagnosis of hearing loss that has not yet spread to speech-related frequency regions of the cochlea (<8 kHz).

    Measured: The incidence of hearing loss at 12 4 weeks after completion of cisplatin-based CRT. Hearing loss will be defined according to ASHA criteria, comparing subjects taking atorvastatin (40 mg) vs. placebo.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Jun 2021
  2. Study start10 Jul 2024
  3. Primary completion1 Aug 2028 (estimated)
  4. Study completion31 Aug 2030 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
224 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04915183
Sponsor's protocol ID
210002
Other IDs
21-DC-0002
Status last verified
31 Aug 2026
First submitted
4 Jun 2021
Last updated
2 Sep 2026
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Atorvastatin in people with Hearing Loss and Head and Neck Cancer, run by National Institute on Deafness and Other Communication Disorders (NIDCD) at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 2 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Katharine A Fernandez, Au.D. ((240) 215-7152, katharine.fernandez@nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

To determine the effectiveness of atorvastatin (20 mg) at reducing the incidence and severity of cisplatin-induced hearing loss in patients with head and neck squamous cell carcinoma (HNSCC). (time frame: Baseline (prior to treatment) to a repeated audiogram at the end of treatment (within 2-4 months of cessation of cisplatin administration).). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Sep 2026.

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