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

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ClinicalTrials.gov Identifier: NCT04915183
Recruitment Status : Not yet recruiting
First Posted : June 7, 2021
Last Update Posted : June 24, 2022
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute on Deafness and Other Communication Disorders (NIDCD) )

Brief 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.

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 2 visits. One before starting cisplatin treatment and within 3 months of completing 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.

Participants in the interventional arm will have 2 additional 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.


Condition or disease Intervention/treatment Phase
Hearing Loss Head and Neck Cancer Drug: Atorvastatin Other: Placebo Phase 3

Show Show detailed description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 414 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Phase III Interventional Study Using Atorvastatin to Reduce Cisplatin-Induced Hearing Loss Among Individuals With Head and Neck Cancer
Estimated Study Start Date : June 29, 2022
Estimated Primary Completion Date : March 1, 2025
Estimated Study Completion Date : December 31, 2025


Arm Intervention/treatment
1
randomization to either placebo or atorvastin
Drug: Atorvastatin
For the interventional arm of the study, subjects will be provided with atorvastatin (20 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.

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

No Intervention: 2
observational



Primary Outcome Measures :
  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). [ Time Frame: Baseline (prior to treatment) to a repeated audiogram at the end of treatment (within 2-4 months of cessation of cisplatin administration). ]
    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).


Secondary Outcome Measures :
  1. To examine the extent to which other statin drugs (and other doses of atorvastatin) reduce the incidence and severity of cisplatin-induced hearing loss in patients with head and neck squamous cell carcinoma [ Time Frame: Baseline (prior to treatment) to a repeated audiogram at the end of treatment (within 4 months of cessation of cisplatin administration). ]
    The secondary 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 in the observational arm of the study. Hearing loss will be defined according to CTCAE criteria and will be compared in subjects taking: 1) any statin other than atorvastatin vs. subjects not taking any statin drug, 2) subjects taking atorvastatin at doses other than 20 mg vs. subjects not taking any statin. Hearing sensitivity will be compared between audiograms collected at baseline (prior to treatment) to a repeated audiogram at the end of treatment (within 4 months of cessation of cisplatin administration).



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

In order to be eligible to participate in either the observational or interventional arms of this study, an individual must meet all of the following criteria as 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
  • Adult patients, male or female, aged >=18
  • Diagnosed with squamous cell carcinoma of the head and neck, confirmed by pathologic review of surgical or biopsy specimen(s), who meets standard clinical and laboratory criteria and will undergo treatment with concomitant cisplatin-based chemotherapy and radiation with curative intent.
  • This includes patients who will be treated with either intensity-modulated radiation therapy (IMRT) or proton radiotherapy, with planned dose to the cochlea of <35 Gy (to limit confounding effects of radiation).
  • Subjects must have hearing thresholds at or better than 70 dB SPL at 1, 2, and 4 kilohertz (kHz) at the time of their baseline audiogram.
  • Ability to provide consent and provision of signed and dated informed consent form

In order to be eligible to participate in the interventional arm of this study, an individual must meet all of the

following criteria:

  • Baseline laboratory tests in the following range: aspartate aminotransferase (AST or SGOT); alanine aminotransferase; creatine phosphokinase, creatinine <1.5x ULN.
  • Ability to take oral medication by mouth or by feeding tube 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.

The investigators will attempt to enroll subjects of diverse race, gender and age. However, our ability to do this will be limited by the demographics of patients typically diagnosed with HNSCC. There is a male predominance, and patients tend to be in their 5th to 7th decades of life ("Cancer of the Oral Cavity and Pharynx - Cancer Stat Facts," n.d.).

EXCLUSION CRITERIA:

An individual who meets any of the following criteria will be excluded from participation in the observational or interventional arms of this study:

  • Patients with a Type B tympanogram.
  • Patients with bilateral cochlear implants will be excluded.
  • Patients with a history of prior treatment with platinum chemotherapy drugs will be excluded.
  • Patients for whom additional adjuvant platinum-based chemotherapy is planned after the completion of concomitant chemoradiation (e.g., patients with nasopharyngeal carcinoma) will be excluded.
  • Staff members of the NIDCD Sections and of the lead site investigators that are headed by the PI and LAI will be excluded.
  • Children will be excluded because HNSCC in children under age 18 is exceedingly rare.

An individual who meets any of the following criteria will be excluded from participation in the interventional arm of this study:

  • Current use of cimetidine, spironolactone, ketoconazole, cyclosporine, or protease inhibitors for HIV or hepatitis C
  • Pregnancy, lactation, or plan to become pregnant
  • Known allergic reactions to components of atorvastatin or the placebo
  • Other severe or unstable medical conditions for which clinical site PI believes increase risk to safety or being able to complete study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04915183


Contacts
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Contact: Katharine A Fernandez, Au.D. (301) 496-5699 katharine.fernandez@nih.gov
Contact: Lisa L Cunningham, Ph.D. (301) 443-2766 cunninghamll@mail.nih.gov

Locations
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United States, Maryland
National Institutes of Health Clinical Center
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)    800-411-1222 ext TTY8664111010    prpl@cc.nih.gov   
Sponsors and Collaborators
National Institute on Deafness and Other Communication Disorders (NIDCD)
Investigators
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Principal Investigator: Lisa L Cunningham, Ph.D. National Institute on Deafness and Other Communication Disorders (NIDCD)
Additional Information:
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Responsible Party: National Institute on Deafness and Other Communication Disorders (NIDCD)
ClinicalTrials.gov Identifier: NCT04915183    
Other Study ID Numbers: 210002
21-DC-0002
First Posted: June 7, 2021    Key Record Dates
Last Update Posted: June 24, 2022
Last Verified: April 14, 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute on Deafness and Other Communication Disorders (NIDCD) ):
Audiogram
Statin
Chemotherapy
Squamous Cell Carcinoma
Additional relevant MeSH terms:
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Head and Neck Neoplasms
Hearing Loss
Deafness
Neoplasms by Site
Neoplasms
Hearing Disorders
Ear Diseases
Otorhinolaryngologic Diseases
Sensation Disorders
Neurologic Manifestations
Nervous System Diseases
Atorvastatin
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors